You are on page 1of 48

Guidelines to Antiretroviral Drug Therapy in Kenya

Table of Contents
Guidelines to Antiretroviral Drug Therapy in Kenya......................................................................................1 FOREWORD..........................................................................................................................................1 ACKNOWLEDGMENT ............................................................................................................................2 CHAPTER ONE: INITIATING ANTIRETROVIRAL THERAPY...............................................................3 1.1 Introduction................................................................................................................................3 1.2 Guidelines to making a diagnosis of HIV infection.....................................................................5 1.3 Laboratory Diagnosis of HIV infection........................................................................................6 1.4 Goals of therapy.........................................................................................................................6 1.5 When to start therapy.................................................................................................................6 1.6 Risks and benefits of delayed initiation of therapy and of early therapy in the Asymptomatic HIV−Infected Patient ................................................................................................................8 . 1.7 Antiretroviral profile....................................................................................................................8 1.8 What drug combination to start with?.......................................................................................10 CHAPTER TWO: MONITORING AND CHANGING THERAPY...........................................................12 2.1 Surrogate markers...................................................................................................................12 2.2 Resistance testing....................................................................................................................13 2.3 How often should CD4 Cell Count and Viral Load be performed (Frequency)........................13 . 2.4 Treatment failure......................................................................................................................13 2.5 Reasons for non−adherence ....................................................................................................14 2.6 Considerations for changing a failing regimen.........................................................................14 2.7 Guidelines for changing an antiretroviral regimen for suspected drug failure..........................15 2.8 Potential options for changing therapy*...................................................................................15 CHAPTER THREE: PHARMACOTHERAPEUTICS OF ARVS............................................................17 3.1 Characteristics of available antiretroviral drugs.......................................................................17 3.2 Pharmacokinetic properties of Antiretrovirals ...........................................................................20 CHAPTER FOUR: GUIDELINES FOR THE USE OF ANTIRETROVIRAL DRUGS IN PAEDIATRIC HIV INFECTION ............................................................................................................21 4.1 Overview..................................................................................................................................22 4.2 Diagnosis of HIV infection in children .......................................................................................22 4.3 When to initiate treatment........................................................................................................22 4.4 Initiation of treatment ...............................................................................................................23 . 4.5 Agents to choose for initial treatment.......................................................................................23 4.6 Dosages for paediatric formulations .........................................................................................23 4.8 Monitoring................................................................................................................................25 4.9 When to change therapy..........................................................................................................25 CHAPTER FIVE: MANAGEMENT OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTED PREGNANT WOMEN AND PREVENTION OF MOTHER TO CHILD TRANSMISSION (MTCT) OF HIV .................................................................................................................................................26 5.1 Overview..................................................................................................................................26 5.2 Factors affecting mother to child transmission.........................................................................26 5.3 Outline antenatal, intrapartum postpartum and postnatal care................................................27 5.4 Antiretroviral Therapy to prevent MTCT...................................................................................28 CHAPTER SIX: SPECIAL CONSIDERATIONS...................................................................................28 6.1 Acute retroviral syndrome (ARVS)...........................................................................................28 6.2 ARV drugs and the treatment of Tuberculosis.........................................................................29 6.3 Immune recovery syndrome .....................................................................................................29 CHAPTER SEVEN: WHEN TO STOP TREATMENT (INTERRUPTIONS)..........................................30 7.1 Structured treatment interruptions (STI's)................................................................................30 7.2 Non structured treatment interruption......................................................................................31 CHAPTER EIGHT: GUIDELINES FOR POST EXPOSURE PROPHYLAXIS......................................31 8.1 Treatment of exposure sites .....................................................................................................31 8.2 Timing of post − HIV exposure prophylaxis initiation...............................................................31 8.3 Assessment of exposure risk...................................................................................................31 8.4 Post − HIV exposure prophylaxis.............................................................................................32 8.5 Recommended HIV serology after exposure...........................................................................32 8.6 Management of health care workers with accidental exposure to HIV infection......................32 8.7 Management of hospital staff with sharp injury or exposure to blood and body fluids.............34 8.8 Management of non occupational exposure to HIV infection...................................................34 8.9 Management of non−sexual and non occupational Exposures to HIV .....................................35 CHAPTER NINE: ACCESS TO DRUGS IN KENYA............................................................................36

i

Table of Contents
Guidelines to Antiretroviral Drug Therapy in Kenya APPENDICES .......................................................................................................................................36 I. Drug to drug interactions.............................................................................................................36 II. Drug to drug interactions (continued).........................................................................................37 III. Drug Interactions Between Antiretrovirals and Other Drugs.....................................................38 IV. Nucleoside Reverse Transcriptase Inhibitors (NRTIS).............................................................39 V. Drug Interactions: Protease Inhibitors.......................................................................................40 VI. Drug Interactions: Protease Inhibitors and Non−Nucleoside Reverse Transcriptase Inhibitors − Cont.....................................................................................................................40 VII. Drug That Should Not be Used With Antiretrovirals................................................................41 VIII. Drugs that should not be used with Protease Inhibitors Antiretrovirals..................................42 IX. HIV−related drugs with overlapping toxicities...........................................................................43 X. Anti−retroviral therapy for preventing MTCT ..............................................................................43 BACK COVER......................................................................................................................................44

ii

NASCOP. Mohammed. The mainstay of managing HIV/AIDS epidemic is prevention and advocacy for behaviour change. However. FOREWORD Acquired Immune Deficiency Syndrome (AIDS) is a rapidly growing public health problem in Kenya. In less than a decade. Prof. M Dr. rapidly fatal illness into a chronic disease. When using an unfamiliar drug. Currently drugs for opportunistic infections are provided in public hospitals including anti−TB drugs. clinicians are urged to confirm dosages before prescribing or administering the drug. Ist edition February 2001 Copyright ' 2001. no responsibility can be taken for errors or omissions. 1 . Aluoch.O.Guidelines to Antiretroviral Drug Therapy in Kenya Enquiries regarding these Clinical Guidelines should be addressed to: Director National Aids and STD Control Programme (NASCOP) Ministry of Health P.N. Kenya hospitals continue to offer care to many patients who occupy beds for long with recurrent complications. I. Already more than 2 million are estimated to have been infected in Kenya as from 1985 when the first case of AIDS was recognized. Hardika. AIDS has evolved from a fulminant. Muia Ndavi − Nairobi Hospital − Nairobi Hospital − University of Nairobi − NASCOP − University of Nairobi Correct Citation National Aids and STD Control Programme. Mbori Ngacha Dr.co.L. 2001 Clinical Guidelines on antiretroviral Therapy. Box 19361 Nairobi. Nairobi. Lule G. The Guidelines are meant for the use of trained clinicians who have primary responsibility for treatment of HIV/AIDS patients. Government of Kenya EDITORS Dr. However. Chebet K. − NASCOP − University of Nairobi OTHER EDITORIAL TEAM MEMBERS Dr. A Dr.ke NOTES ON DRUG DOSAGES Every effort has been made to ensure that drug dosages and treatment schedules are correct and in accordance with current accepted medical practice. Kenya Telephone: +254 2 719502/729549 Email: headnascop@iconnect. Ministry of Health. S Dr. With advancing technology new powerful antiretroviral drugs regimens have become available and now form part of total continuum care of HIV/AIDS patients.

the University of Nairobi and private hospitals. and monitoring will require capacity building of staff hence need for standard treatment protocols for providing the highest quality and most cost−effective health care. Dr.M. F Dr.K. Karanja Joseph Dr. DIRECTOR OF MEDICAL SERVICES FEBRUARY. 2002 ACKNOWLEDGMENT These guidelines are a result of the collaborative effort of many people. Dr. Lule G. MUGA. Dr. The alphabetical list of the main contributors are given below. Dr. Kevin De−Cock Prof. Lwanga Charles Prof. OGW. whose dedication and hard work is gratefully acknowledged. Gilbert Dr. the initial edition requires regular revisions and updates in terms of content and context. Kokwaro. Hardika Shah Dr. Prof. It is hoped that these stakeholders will participate in training of doctors and nurses in rural hospitals where many AIDS patients are hospitalized. Dr. Chebet K. With the publication of these Guidelines to antiretroviral drug therapy. Koskei K. Mati J. Aluoch A.L. Bhatt K. Availability of retroviral drugs to Kenyans who need them is the subject of debate but no doubt the government will soon put in place legal framework to increase access to these drugs. These drugs will be used along−side priority advocacy for behaviour change at all levels in Kenya. RICHARD O. Ilako. DR. Anzala O.G − Kenya Association of Physicians − University of Nairobi − University of Nairobi − NASCOP − Ministry of Health − Nairobi Hospital − Kenya Association of Physicians − University of Nairobi − CDC − Director (Kenya) − Wellcome Trust − Chief Pharmacist − Ministry of Health − University of Nairobi − Nairobi Hospital − KOGS 2 . The approach adopted by Kenya in the fight of Aids revolves around the sessional paper No. Like most publications. 4 of 1997 and the National Aids Control Strategy.Proper use of these drugs. Prof. DSM.N. the Ministry is establishing standard regimens for antiviral drug use and monitoring of patients. The manual is the result of considerable collective effort of senior clinicians and pharmacists from the Ministry of Health.

printing and implementation of the guidelines. Mohammed I. Mutungi Alice Dr. Otieno L.M. Qureshi Zahinda Dr. Chairman. P. Abdallah. Shah Sital Dr. D. Mugo Nelly Dr. HIV infection is transmitted through: 3 . Dr. and Dr. Dr. Musoke Rachel Dr.E. Peter Eriki (WHO) and Mr. Patel S. Dr.1 Introduction The Human immunodeficiency virus (HIV) is an RNA retro virus existing in two forms: HIV − 1 which is the commonest cause of infections.S. CHAPTER ONE: INITIATING ANTIRETROVIRAL THERAPY 1. Kenneth Chebet facilitated the harmonization of the various guidelines into one. Andrew Stenton (Nairobi Hospital) for their invaluable contribution. Ochiel Stephen Prof. Mwangi Margaret Dr. and Director −NASCOP Dr. Dr. National AIDS Control Council for their support to this project.B. Wairagu S. Mbori Ngacha Dr. Dr. Dr. A special appreciation is extended to Dr. Owili D. editing. Muia Ndavi Dr. Omondi Ogutu Prof. while HIV − 2 is confined to certain parts of West Africa. Gachara. Muita Jane Dr. M. Dr. Were Edwin − University of Nairobi − NASCOP − Ministry of Health − Kenyatta National Hospital − UNICEF − University of Nairobi − University of Nairobi − University of Nairobi − Kenyatta University Hospital − University of Nairobi − KOGS − University of Nairobi − Kenyatta National Hospital − Kenyatta National Hospital − University of Nairobi − Aga Khan Hospital − KOGS − MP Shah − University of Nairobi − Aga Khan Hospital − Aga Khan Hospital − Kenyatta National Hospital − Moi University The Director of Medical Services.O.T. Marinus Gotink (UNICEF) Dr. Dr. Tesfaldet G.Dr. Warren Naamara (UNAIDS). Ojwang S. Mulindi Sobbie Prof. Nduati Ruth Dr. Richard Muga. Ombuya Godfrey Dr. Dr. Further appreciation goes to Dr. Director. The Ministry of Health gratefully acknowledges the financial assistance from joint United Nations Programme on HIV/AIDS (UNAIDS) and WHO which facilitated the writing.S. M.

• The "rapid developers" (approximately 20% of all cases) who develop AIDS within 5 years following infection. • The "slow developers" (approximately 5% of all cases) who remain asymptomatic for over 10 years without a significant decline in CD4 T cell count. The destruction of T − cell is due mainly to active viral replication. HIV related symptoms may disappear. people can be broadly categorized as follows: • "Average developer" who develop AIDS within approximately 10 years. There is now sufficient evidence that triple combination antiretroviral therapy reduce viral load plasma level to undetectable levels. Using the average time taken for development of acquired immunodeficiency syndrome (AIDS) following HIV infection. and the rate of CD4 T − cell decline. Infection with HIV − 1 results in a progressive destruction of the CD4 lymphocytes.• Sexual contact • Inoculation with infected blood/blood products • Use of contaminated needles • Vertical transmission from mother to child. the incidence of opportunistic infections is reduced and quality of life improves as illustrated in the following two graphs: NATURAL HISTORY OF UNTREATED HIV− 1 INFECTION 4 . determines the rate of immunodeficiency and subsequent development of HIV related opportunistic infections.

338−60 The majority of people infected with HIV in the developing world have no access to the antiretroviral treatment.. Access to antiretroviral treatment must be seen from a more comprehensive outlook of total continuation of care of HIV/AIDS patients. There should be active participation of doctors. CID4T cell counts and clinical assessment on early diagnosis. HIV/AIDS infected pregnant women and children. Educational programmes for physicians and general practitioners committed to HIV/AIDS care aim at avoiding unnecessary or inadequate therapeutic prescriptions.2 Clinical Staging All clients/patients identified to be HIV seropositive should be given the opportunity for on−going counseling and support. For purposes of clinical management. nurses. all individuals diagnosed.Mortality in patients with CD4<100 and use of antiretroviral (ARV) therapy including a protease inhibitor among those patients. as HIV+ should classified according to disease stage as follows:− 5 .2.1 Pretest and Post Test Counselling HIV infection in asymptomatic individuals is often made as a result of a test solicited for routine medical examination required by employers.2 Guidelines to making a diagnosis of HIV infection 1. Post−test counseling should form an integral part of the process of giving back HIV test results. Laboratory monitoring including HIV. All patients undergoing an HIV test should do so after adequate pre−test counseling where they are informed of the nature of the test and the meaning and consequences of a positive test. New England Journal of Medicene 1998 Mar 26. RNA. 1. It is meant to serve as a guide to antiretroviral treatment and we anticipate that these guidelines will trigger development of innovative approaches to better management of patients with HIV/ AIDS in Kenya. insurance schemes. 1.2. patients and their relatives. In symptomatic patients an HIV diagnosis may be made as part of the medical work−up for the patient. choice of combination for antiretroviral management of acute HIV/AIDS. The guidelines provide information on antiretroviral therapy including when to start treatment. post exposure prophylaxis and structured interrupted treatments are indicated. which should be continuous starting from hospital to the community. volunteers. The Kenyan Health worker has an obligation to provide care. or for travel purposes. USA 1994−1997 Source: Palella et al. what drugs to initiate. when to change therapy and therapeutic options to consider when changing therapy.

3 Laboratory Diagnosis of HIV infection Laboratory testing for the diagnosis of HIV infection can be divided into four main categories: • Antibody detection • Antigen detection • Testing for viral nucleic acid (RNA or PRO DNA) • Culturing for the virus Elisa antibody detection is the serological screening test used often to detect HIV Infection.4 Goals of therapy The primary goals of antiretroviral therapy are maximal and durable suppression of plasma viral load. • Restoration and/or preservation of immunologic function. preservation and/or restoration of immunologic function. one for screening and the other for confirmation. • Clinical benefit has been demonstrated in controlled trials only for patients with CD4+T cells <200/mm3. Third generation ELISA's. All decisions to initiate therapy should be based on prognosis for disease−free survival in the absence of treatment.5 When to start therapy The decision to start therapy should be made after considering the patient's acceptance or readiness and the probability of adherence. Tools to Achieve Goals of Therapy • Maximum adherence to the antiretroviral regimen • Rational sequencing of drugs • Preserving future treatment options. It is therefore recommended that for laboratory diagnosis of HIV infection. and the willingness of the patient to accept therapy. two ELISA'S for antibody detection should be done. The strength of the recommendation is dependant on the prognosis as determined 6 .• Acute seroconversion syndrome • Asymptomatic HIV infection • Symptomatic HIV disease 1. most experts would offer therapy at a CD4+T cell threshold <350/mm. • Improvement of quality of life. as determined by the CD4+ cell count and level of plasma HIV RNA shown in Table 5. However. In the event that one ELISA is positive and another negative. Goals of HIV Therapy and Tools to achieve them Goals of therapy • Maximal and durable suppression of Viral load. the potential benefits and risks of therapy shown in Table 4. 1. 1. which use recombinant antigens. • Use of resistance testing in selected Clinical settings where possible. testing for viral nucleic acid (polymorase chain reaction − PCR) can be used for confirmation of the serostatus or Western blot assays. are highly specific and highly sensitive. improvement of quality of life and reduction of HIV related morbidity and mortality. • Reduction of HIV related morbidity and mortality. The two have to be positive for one to make a laboratory diagnosis of HIV − 1 infection.

Cryptococcal Meningitis and Atypical pneumonia's. recognizing that the 3 year risk of developing AIDS in untreated patients is >30%. A few facts however are well known:− • If the CD4 count falls below 200 then one is bound to suffer increasing incidences of opportunistic infections • Although there is theoretical benefit to antiretroviral therapy for patients with CD4T cell counts greater than 200 cells/m3. These risks and benefits are as outlined in the table.by clinical state. In the absence of very high levels of plasma HIV RNA. Severe symptoms) Asymptomatic AIDS. CD4 cell count and viral burden. It may also be advantageous to follow lipid profiles in most patients on antiretroviral therapy. Indication for the initiation of Antiretroviral Therapy in the Chronically HIV−1 infected patient Clinical Category Symptomatic (AIDS. however. • The optimal time to initiate antiretroviral therapy is not known. Urea and electrolytes and liver function tests. The two assessments tests are. 7 . no studies have been conducted to compare immediate against delayed potent therapy.000(bDNA) or >55. Table showing when to start therapy. One should therefore weigh the risks and benefits of delayed and early therapy and discuss them fully with the patient before initiating therapy. useful for monitoring therapy. though controversy exists Some experts would recommend initiating therapy. Asymptomatic >30. Initiating Therapy in established HIV infection Before initiating therapy in any individual the following basic evaluation should be performed • Complete history and physical examination • Total blood count.000(RT−PCR) In resource poor setting. Clinical outcomes data after initiating therapy are lacking. • CD4 (T−lymphocyte count) • Viral load (Plasma HIV RNA) Additional investigations should be targeted towards establishing factors leading to symptomatology including common opportunistic infections such as Tuberculosis. initation for symptomatic patients can be started even when CD4 or viral load assessment tools are absent. some would defer therapy and monitor the CD4 + cell count and level of plasma HIV RNA more frequently. Initiating Therapy in Patients with Asymptomatic HIV infection This is still controversial. Asymptomatic CD4+ Cell Count Any Value CD4+ cells<200/mm3 CD4+ cells>200/mm3 but < 350/mm3 CD4+T cells >350/mm3 Plasma HIV RNA Any Value Any Value Any Value Recommendation Treat Treat Treatment should generally be offered.

1. condoms and safer sex practices).. faithfulness. • Lower risk of resistance with complete viral suppression.1. inconvenience) • Avoid drug−related adverse effects. • Limitation of future antiretroviral treatment options. These antiretroviral drugs fall in three different classes and work at different sites on the HIV virus. 8 .e. What is HAART? Highly Active Anti−retroviral Therapy is a combination of three or more antiretroviral drugs in the treatment of HIV infection. • Delay in development of drug resistance • Preserve maximum number of available and future drug options when HIV disease risk is highest. drugs was the nucleoside analogues.g. They act by incorporating themselves into the DNA of the virus thereby stopping the building process.6 Risks and benefits of delayed initiation of therapy and of early therapy in the Asymptomatic HIV−Infected Patient Risks and benefits of early therapy Benefits of early therapy • Control of viral replication easier to achieve and maintain • Delay or prevention of immune system compromise. • Earlier development of drug resistance. Risks and benefits of delayed therapy Benefits of delayed therapy • Avoid negative effects on quality of life (i. The resulting DNA is incomplete. if viral suppression is suboptimal. Risks of delayed therapy • Possible risk of irreversible immune system depletion • Possible greater difficulty in suppressing viral replication • Possible increased risk of HIV transmission • It is important to note that the risk of viral transmission still exists. Nucleoside analogue Reverse Transcriptase Inhibitors (NRTIs) The first effective class of anti−retroviral. and antiretroviral therapy cannot substitute for primary HIV prevention measures (e.7 Antiretroviral profile The gold standard of anti−retroviral therapy is HAART. • Possible decreased risk of HIV transmission Risks of early therapy • Greater cumulative drug−related adverse affects. Abstinace.

Protease Inhibitors Saquinavir hard− gel (SQV) Saquinavir soft gel (SQV) Ritonavir** (RTV) Indinavir (IDV) Nelfinavir** (NFV) Amprenavir^ (AMV) Lopinavir + Ritonavir^ Capsules. 200mg Tablets. 100mg. 100mg 600mg OD 200mg BD 600mg BD Drugs marked ^ are not currently available in Kenya and drugs marked ** are available in pediatrics formulations. 25mg Tablets. 100mg Capsules.Name and class of drug Nucleoside analogue Reverse Transcriptase Inhibitors (NRTIs) Zidovudine (AZT)** Didanosine (ddl)** Lamivudine (3TC)** Stavudine (d4T)** Strength of preparation Adult Dosing Capsules. 100mg Tablets. 250mg Tablets. 600Jmg TID 1200mg TID 600mg BD 800mg TID 1250mg BD or 750mg TDS 1200mg BD 400mg Lopinavir + 100mg Ritovavir BD Capsules. 300mg The second class of antiretroviral drugs are the Non−Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) which stop HIV production by binding directly onto reverse transcriptase preventing the conversion of RNA to DNA. 200mg Tablets. 200mg Capsules.75mg Capsules. 9 . 30mg 250−300mg BID 100−200mg BD 150mg BID 40mg BID 30mg BID 0. they act in a completely different way. Non−Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Efavirenz (EFZ) Nevirapine (NVP) Delavirdine (DLV) Protease Inhibitors The last class of antiretroviral drugs are the Protease Inhibitors which work at the last stage of the virus reproduction cycle.75mg TO 300mg BD Zalcitabine (ddC) Abacavir (ABC) Non−Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Tablets. 300mg Capsules (13. 150mg Capsules.3mg Ritonavir). 200mg Capsules.3mg Lopinavir + 33. 40mg Capsules. 200mg Capsules. These drugs are called non−nucleoside inhibitors because even though they work at the same stage as nucleoside analogues. They prevent HIV virus from being successfully assembled and released the infected cell. 0.

and insulin resistance Drug Interaction Complications Mild to severe inhibition of cytochrome P450 pathway.e.. Resistance requires multiple mutations Targets HIV at two steps of viral replication (RT and PI) Sparing of PI−related side effects Generally easier to use and adhere to compared with Pis Possible Disadvantages May be difficult to use and adhere to Long−term side effects may include lipodystrophy. Ritonavir is most potent inhibitor.> 100 000 copies/ml may be suboptimal Fewer drug−drug interactions Pis Preserves Pis for later use Resistance usually leads to cross resistance across entire NNRTI class Preserves both PI and NNRTI classes for later use Limited cross−resistance within the NRTI class Triple NRTI Regimen (NNRTI −and PI−sparing) Generally easier to Use and adhere to compared with PIs Sparing of PI and NNRTI side effects Resistance to 1 NRTI does not confer cross−resistance to entire class Generally manageable drug interaction problems 10 .8 What drug combination to start with? Initiation of Therapy Leading Regimens to consider • 2 Nucleoside RTI's + Protease Inhibitor − NNRTI sparing • 2 Nucleoside RTI's + Non−Nucleoside RTI − PI sparing • 3 Nucleoside RTI's (including abacavir) − PI and NNRTI sparing Advantages and disadvantages of class sparing regimens Regimen PI based HAART regimen (NNRTI−sparing) Possible Advantages clinical. but this effect can exploited to boost levels of other Pis Impact on future Options Preserves NNRTI for use in treatment failure Resistance primes for cross−resistance with other Pis NNRTIs−based HAART regimen (PI−sparing) Comparability to PI−containing regimens with regard to clinical endpoints unknown Resistance Conferred by single or few mutations Compatibility to PI−containing regimens with regard to clinical endpoints unknown Long−term virologic efficacy with high baseline plasma vital load (i.1. and mmunologic efficacy well−documented. Continued benefits sometimes seen despite viral breakthrough. virologic.* hyperlipidemia.

Kenya is a member of the steering team and the recommended 1st line drugs will be indicated in the 2nd Edition of this booklet. Didanosine. Lamivudine. There is an interim WHO ARV Treatment Working Group drafting guidelines for Resource Poor Settings. drug potency and other factors detailed in this book. Strongly recommended Column A Efavirenz Indinavir Nelfinavir Ritonavir + Indinavir Ritonavir + Lopinavir Ritonavir + Saquinavir Recommended as alternatives Column A Abacavir Column B Column B Stavudine + Didanosine Stavudine + Lamivudine Zidovudine + Didanosine 11 . Didanosine. Efavirenz • Stavudine. have not been proven to be strictly associated with use of protease inhibitor−containing regimens. such as lipodystrophy. Drugs are listed in alphabetical and not in priority order. Nelfinavir • Stavudine.• Some side effects being attributed to protease inhibitor therapy. Lipodystrophy has also been discerened uncommonly in patients on NRTIs alone and patients on other antiretroviral therapy. Antiretroviral drug regimens are comprised of one choice each from column A and B. Nevirapine The choice of regimen should take consideration of patient's affordability. The following table of recommendations is based on IAS and DHHS guidelines for antiretroviral therapy. Possible first line Regimen for Adults (with substitutions) • Zidovudine/Lamivudine/Nelfinavir (or LPV or Indinavir) − Stavudine for Zidovudine (in case of toxicity) • Zidovudine/Lamivudine/Efavirenz (or Nevirapine) − Stavudine for Zidovudine (in case of toxicity) • Zidovudine/Lamivudine/Abacavir − Stavudine for Zidovudine (in case of toxicity) • Stavudine.

Coincident with the body's humoral and cellmediated immune response.Didanosine + Lamivudine Amprenavir Delarvidine Nelfinavir + Saquinavir Ritonavir Saquinavir No recommendation/ insufficient data Hyroxyurea in combination with antiretroviral drugs Ritonavir + Amprenavir. RNA levels decline. In HIV−1 infection. recommendations for the use of HIV RNA copy number in deciding to initiate and change antiretroviral therapy in infected adults have been developed. also known as Helper T−cells. During the period of primary infection in adults. The CD4 cell count is a laboratory marker of the strength of one's immune system. Viral Load: Viral burden in peripheral blood can be determined by using quantitative HIV RNA assays. They control both arms of the immune system (humoral and cellular). Several studies conducted among adults have indicated that infected persons with lower HIV copy number have slower progression and improved survival compared with those with high HIV RNA copy numbers. Ritonavir + Nelfinavir Not recommended/should not be offered All monotherapies whether from column A or B including Hydroxyurea Column A Saquinavir (Invirase) except with Ritonavir Column B Stavudine + Zidovudine Zalcitabine + Didanosine Zalcitabine + Lamivudine Zalcitabine + Stavudine Zidovudine + Zalcitabine CHAPTER TWO: MONITORING AND CHANGING THERAPY 2.e. HIV RNA copies initially rise to high levels. On the basis of such data.1 Surrogate markers CD4 + Lymphocytes CD4 cells. Normal CD4 counts in adults range from 500−1800 cells per cubic millimeter of volume.HIV−I infection targets these CD4 cells resulting in killing of those infected as well as those not yet infected. CD4 cell count is used to determine the progress of HIV disease i. 12 . are a type of lymphocytes which play an important role in immune system. (staging) and predicts the risk of developing complications.

and LFTs) 2. Many studies in patients on treatment have shown strong associations between the presence of drug resistance and failure of the antiretroviral therapy.3 How often should CD4 Cell Count and Viral Load be performed (Frequency) A CD4 cell count and viral load titer are obtained as part of a baseline laboratory data when initial diagnosis of HIV infection is made or prior to the initiation of antiretroviral drugs. or dementia. The degree of suppression provided by a treatment regime is therefore. wasting.5 log 10 or A persistent increase in viral load following a period of adequate suppression. There are mainly 2 types of resistance testing which unfortunately are not yet readily available in Kenya. Resistance assays may assist clinicians in individualizing initial as well as subsequent antiretroviral treatment regimens for their patients. They may involve sequencing of the entire RI and Protease genes while others go for selected mutations that are known to confer drug resistance. If the regimen is maintained.2 Resistance testing In the majority of patients who have never received antiretroviral therapy. Although available they are more expensive and time consuming to perform. or non−mutant virus predominates. wasting.2. Resistance testing is recommended for persons on anti−retroviral treatment whose viral is increasing and CD4 cell count is declining. During therapy the disappearance or suppression of wild−type virus creates the environment in which the mutant virus can become the dominant species. ARV Failure: Causes 13 . a critical factor in the emergence of HIV drug resistance. Clinical Failure Development of new opportunistic infections. U/E.4 Treatment failure Virologic Failure Failure to reduce the viral load to an undetectable level or Failure to reduce the viral load by at least 2 to 2. the tests for CD4 count and viral load titer should be performed every three moths thereafter along with other laboratory studies (Full Haemogram. the wild type. or dementia or Failure to resolve pretreatment opportunistic infections. 2. Both tests should be repeated about four weeks after starting antiretroviral therapy. In general resistance testing may be useful in the setting of virologic failure of antiretroviral therapy or in acute HIV infection. Phenotyping Assays These assays measure the ability of viruses to grow in various concentrations of antiretroviral drugs. Immunologic Failure Failure to restore the CD4 count to more than 200 cells/mm3 or Failure to significantly increase CD4−cell count or A persistent decline in CD4−cell counts after a period of immune reconstruction. Genotypic Assays These detect drug resistance mutations that are present in the relevant viral genes.

altered absorption or metabolism of the drug. plasma HIV RNA levels measured on two separate occasions. the decision to change regimens should be approached with careful consideration of several complex factors. antiretroviral therapy should maximally suppress viral replication to below levels capable of being detected with HIV RNA assays. reason for treatment failure. at least two and preferably three new drugs should be selected that are not subject to anticipated crossresistance to drugs given previously. should be obtained.i) Patient Factors • Adherence failure ii) Clinical Factors • Patient selection iii) Viral Factors • Resistance 2. These factors include: recent clinical history and physical examination. potential resistance patterns from prior antiretroviral therapies and potential for compliance/tolerance. and poor patient adherence to a regimen due to either poor compliance or inadequate patient education about the therapeutic agents. Failure of a regimen may occur for many reasons. Viral resistance to antiretroviral drugs is an important. Optimally and when possible. but not the only. this is based on the current understanding of strategies to prevent drug resistance. it is important to carefully assess patient compliance prior to changing antiretroviral therapy. In the case of drug failure where more than one drug had been used. the regimen should be changed entirely to drugs that have not been taken previously. it is appropriate to substitute one or more alternative drugs of the same potency and from the same class of agents as the agent suspected to be causing the toxicity.6 Considerations for changing a failing regimen As with the initiation of antiretroviral therapy. A detailed history of current and past antiretroviral medications. and preparation of the patient for the implications of the new regimen. VIROLOGIC CONSIDERATION FOR CHANGING THERAPY Ideally. assessment of adherence to medications. as well as other HIV related medications. multi−drug pharmacokinetics that adversely affects therapeutic drug levels.5 Reasons for non−adherence • just forgetting • Regimen complexity • Side effects • Substance abuse • Fear of medications • Denial of need for treatment 2. Genetically distinct viral variants emerge in each HIV−related individual over time after initial infection. In the latter case. 14 . Other factors that influence decisions include remaining treatment options in terms of potency. including initial viral resistance to one or more agents. In this regard. It is important to distinguish between the need to change therapy due to drug failure versus drug toxicity. absolute CD4T lymphocyte count and changes in these counts. Viruses with single drug resistance mutations exist even prior to therapy. With triple combinations of drugs.

intolerance or no−adherence. 2. single agents can be changed or dose reduced in the event of drug intolerance.Consensus recommendations have been developed using plasma HIV RNA measurements to guide changes in antiretroviral therapy for HIV infected adults. substitute single drug if known Change to simplified regimen with equal potency substitute single drug if known.7 Guidelines for changing an antiretroviral regimen for suspected drug failure Criteria for changing therapy include a suboptimal reduction in plasma viremia after initiation of therapy. it is. b) HIV RNA has not decreased to undetectable levels after 4−6 months of therapy. For patients with no rational alternative options who have virologic failure with return of viral load baseline (pretreatment levels) and declining CD4+T cell count. When the decision to change therapy is based on viral load determination. IMMUNOLOGIC CONSIDERATION FOR CHANGING THERAPY CD4 + lymphocyte count and percentage are independent predictors of disease progression. for patient with limited options. Many patients have limited options for new regimens of desired potency. In some cases. preferable to confirm with a second viral load test. Distinguish between the need to change regimen due to drug intolerance or inability to comply with the regimen versus failure to achieve the goal of sustained viral suppression. re−appearance of viremia after suppression to undetectable. and declining CD4+T cell numbers. HIV RNA above target. it is important to use at least two new drugs and preferably to use an entirely new regimen with at lease three new drugs.8 Potential options for changing therapy* Reasons for change Toxicity or intolerance HIV RNA suppressed below target HIV RNA suppressed but still above target And fewer than 8−16 weeks with therapy. more than 8−16 weeks with therapy or prior successes. This especially applies in late stage disease. do not change a single drug or add a single drug to a failing regimen. Normal CD4 counts in adults in Kenya range from 500−1800 cells per millimeter of volume. but adherence problems present HIV RNA above target. there should be consideration for discontinuation of antiretroviral therapy. more than 8−16 weeks with therapy. Consider changing antiretroviral therapy if there is a rapid and substantial decrease in absolute CD4 + − lymphocyte count (a> 30% decline in < 6 months). more than 8−16 weeks Difficulty with adherence HIV RNA suppressed below target. Consider changing therapy if: a) HIV RNA levels drop less than ten−fold (I log) after 8 weeks of therapy. in some of these cases it is rational to continue the prior regimen if partial viral suppression was achieved. 2. Change entire regimen 15 . HIV RNA above target. Experience is limited with regimens using combinations of two protease inhibitors or combinations of protease inhibitors with Nevirapine and Delavirdine. In general. Change Change the offending drug (if discernible) Change offending drug if discernible Change entire regimen Change to simplified regimen with equal potency. regimens identified as sub−optimal for initial therapy are rational due to limitations imposed by toxicity. significant increases in plasma viremia from the nadir of suppression.

16 . IDV. NFV + NNRTI. weeks of therapy Continue current regimen. OR NNRTI + IDV RTV + IDV 2 NRTIs + NNRTI 2 NRTIs 2 new NRTIs + a protease inhibitor 2 new NRTIs + a protease inhibitor 2 new NRTIs + RTV + SQV 1 new NRTI + 1 NNRTI + a protease inhibitor 2 protease inhibitors + NNRTI 1 NRTI 2 new NRTIs + a protease inhibitor 2 new NRTIs + NNRTI 1 new NRTI + 1 NNRTI + a protease inhibitor These alternative combinations are still being studied in clinical trials and will be amended as more information is published. Change entire regime Possible Regimens for patients who have failed initial Antiretroviral Therapy: Possible Second line Regimens for Treatment Failure • Following AZT/3TC/NFV − d4T/ddl/EFZ or − d4T/ddl/LPV or − d4T/ddl/IDV • Following AZT/3TC/EFZ(or NVP) − d4T/ddl/NFV or − d4T/ddl/LPV. assess consider intensification. or NFV + SQV SQV + RTV. Failure to reach target viral load within adherence 8−16. or NNRTI ID** SQV + RTV**. or SQV + RTV. NFV + SQV Saquinavir RTV + SQV. Failure to reach target viral load within 24−36 weeks Change entire regime of therapy Prior success but now confirmed drug faiture. • Following AZT/3TC/NFV − d4T/ddl/EFZ or − d4T/ddl/LPV or − d4T/ddl/IDV Prior Regimen 2 NRTIs + Nelfinavir Ritonavir Indinavir New Regimen (Not listed in priority order) 2 new NRTIs RTV.Virologic failure adherence. or NNRTI + RTV.

health−care providers should inform their patients of the need to discuss any new drugs. 30mg for BD Take without Pancreatitis. Zidovudine 300mg) tablets (A) Stavudine. particularly the Pis and NNRTIs whose metabolism involves the hepatic cytochrome P 450 (CYP450) enzyme pathway. Zalcitabine and Zidovudine. Renal function tests 17 .g. that they may consider taking. ability to adhere to treatment regimens. As a result. Nelfinavir. there are three classes of drugs used in the management of HIV infected patients.1 Characteristics of available antiretroviral drugs Currently.CHAPTER THREE: PHARMACOTHERAPEUTICS OF ARVS 3. Clinical issues such as drug toxicity. Some of these Pis and NNRTIs (i. two NNRTIs and a PI). and ddl may combine with the direct effects of HIV to render the drugs intolerable. CYP450 inhibitors have the potential to increase blood levels of drugs metabolized by this pathway. and Delarvidine) inhibit the CYP450 pathway. The Non−Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) include Efavirenz. As most patients will be multiple drug therapy. Hepatotoxicity associated with certain Pis may limit the use of these drugs. however. Adding a CYP40 inhibitor can sometimes improve the pharmacokinetic profile of selected agents (e. Indinavir. these interactions can also result in life−threatening drug toxicities. Amprenavir. Lamivudine. Nevirapine. Characteristics Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Nucleoside analogues Combivir (Lamivudine 150mg.g. drug interactions and laboratory abnormalities should be considered when initiating therapy and during treatment.g. others (e. and a combination of Lopinavir and Ritonavir. d4T. especially in patients who have underlying liver dysfunction. The absorption and half−life of certain drugs may be altered by anti retrovirals. Patients who have been offered antiretroviral treatment should be managed with a maximally suppressive regimen (e. the choice of which antiretroviral agent to use must be made with consideration given to potential drug interactions and overlapping drug toxicities. Zerit 30mg & 40mg Dose 1 tablet Frequency BD Dietary restrictions Major side effects Same as Lamivudine and Zidovudine Lab monitoring Liver function tests. Indinavir.e. d4T. and Delarvidine. adding Ritonavir therapy to the hard−gel formulation of Saquinavir) as well as contribute an additive antiviral effect. Other issues to be considered are factors such as wasting and anorexia which may prevent patients from adhering to dietary requirements for efficient absorption of certain protease inhibitors. Didanosine. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) include Abacavir. Nevirapine) induce the CYP450 metabolism. Peripheral regard to meals neuropathy. I. Lactic acidosis with hepatic Liver function tests. and careful attention should be given to the relative risk versus benefits of specific combinations of agents. including over−the counter agents and alternative mediations. Stavudine. Ritonavir. Bone marrow suppression associated with AZT and the neuropathic effects of ddC. Nelfinavir. Thus. Ritonavir. Protease Inhibitors including Saquinavir. 40mg for patients over 60kg. the clinician should be alert to the potential for multiple drug interactions.

steatosis is a rare but potentially life−threatening toxicity with use of NRTIs. TDS Do not take magnesium/ aluminum containing snack. 300mg Ziagen 300mg tablets (A) BD Liver function tests.75mg tablets (A) 0. Peripheral neuropath. malaise of fatigue and loss of appetite. Liver function tests. Alcohol increases ABC levels to 41 % Hypersensitivity reaction (can be fatal). steatosis. Complete blood count. Pancreatitis. Diarrhea Lactic acidosis with hepatic steatosis is a rare but potentially life threatening toxicity with the use of NRTIs. Take without regard to meals. rash. Liver function tests. Should not be prescribed to patients requiring dose adjustment 2) Protease Inhibitors (PIs) Protease Inhibitor Dose Frequency TDS Lab Monitoring Dietary restrictions Major side effects 18 . Stomatitis. Liver function tests. headache. Lactic acidosis with hepatic steatosis is a rare but potentially life threatening toxicity with the use of NRTIs Take without regard to meals. severe hepatomegally.375mg (NA) 0. SOB) Lactic acidosis with hepatic steatosis−rare.capsules (A) patients under 60kg. nausea. Complete blood count. Lactic acidosis with hepatic steatosis is a rare but potentially life−threatening toxicity with NRTIs. Nausea. Didanosine. Epivir 150mg tablets (A) 150mg BD BD Take 30 min before or 2 hours after food. Retrovir 100mg capsules (A) 300mg (NA) 200mg TDS BD Take without Bone marrow regard to meals suppression: Anemia and/or Neutropenia. BD Take without regard to meals. Complete blood count. Complete blood count. Respiratory symptoms may also be component (sore throat. Abacavir. cough. Subjective complaints: GI intolerance. ABC.75mg Liver function tests. 150 and 200mg tablets Lamivudine. Rash. insomnia. vomiting. Renal function tests Complete blood count. Zalcitabine. asthenia. Complete blood count with differentials. Serum amylase levels for individuals at risk for pancreatitis. ZDV. Serum amylase. ddC. Routine serum chemistry. >60mg−200mg ddl. lactic acidosis. Peripheral neuropathy. (RBC indices and Patelet count. Pancreatitis Liver disease/hepatitis. Videx 25 & 100mg tablets <60mg 125mg (A) 50. Fever. AZT. Hivid 0. Zidovudine. 3TC.

This may improve tolerability Ritonavir Norvir 100mg capsules (A) 600mg BD NB. nausea and diarrhea. Dizziness. Saquinavir (soft gel) formulation Fortovase 200mg capsules 1200mg TDS Complete blood count and routine blood chemistry periodically. Day 3−5: 400mg BD. Day 6−13 500mg BD. Misc. Hepatitis Pancreatitis Asthenia Taste perversion Hyperglycemia Fat redistribution and lipid abnormalities Possible increased bleeding episodes in patients with hemophilia. Renal function tests. This increase levels 6−fold 19 . vomiting.Nelfinavir. or low fat meal. redistribution and lipid abnormalities Possible Indinavir Crixivan 400mg capsules (A) 200mg capsules (NA) 800mg TDS To be taken on an empty stomach 1 hour before of 2 hours after meal. asthenia. AST and CK monitoring Liver function tests. nausea. Hyperglycemia Fat. GI intolerance. Headache. Plenty of fluids to be taken approx. Parenthesis− circumpolar and extremities. Liver function tests and serum lipid/lipoprotein profile every 2−4 weeks. diarrhea. GI intolerance. alopecia. Viracept 250mg tablets (A) 750mg or 1250mg BD Routine clinical chemistry including HB. Hyperglycemia Fat redistribution and lipid abnormalities Possible increase bleeding episodes with hemophilia. diarrhea. Should be refrigerated. Possible increased bleeding episodes in patients with hemophilia Nephrolithiasis. nausea. rash. thrombocytopenia. Complete blood count with differentials and routine blood chemistry every 2−4 weeks. blurred vision. Hyperglycemia Fat redistribution and lipid abnormalities. Day 14−: 600mg BD. May take with skim milk increased bleeding episodes in patients with hemophilia. 1. GI intolerance. neutropil and lymphocyte counts as well as ALT. Dose escalation required for Ritonavir to improve tolerability Day 1−2: 300mg BD. Take with meals.5 L per day. Take within 2 hours of a meal. GI intolerance. Take with large meal. metallic taste.: headache. Oral bioavailability is erratic. Headache. abdominal pain and dyspepsia. Hyperglycemia Fat redistribution and Saquinavir (hard gel) formulation Invirase 200mg capsules (A) 600mg TDS Complete blood count and routine blood chemistry periodically. nausea. Take with meal or snack Diarrhea. Complete blood count Routine blood chemistry.

GI intolerance. Capsules and solution not interchangeable on mg per mg basis. Lopinavir + Ritonavir Kaletra−133. nausea vomiting. NB. 200mg tablets (NA) TDS Take without regard to meals: separate dosing with ddl or antacids by 1 hour.2 Pharmacokinetic properties of Antiretrovirals Drug Oral Bioavailability Serum Half−life Intracellular Half−life Elimination 20 . 100mg capsules− (NA) Nevirapine Viramune 200mg capsules − (A) 600mg Dose Frequency OD Lab Monitoring Routine blood chemistry. Dietary restrictions Major side effects High fat meals Rash.3 mg Ritonavir (capsules). should be avoided Central nervous system symptoms Take without regard to meals Rash Hepatitis 200mg. Rash (usually mild) Headache Nausea Vomiting 3.5ml/kg BID oral solution maximum 2800mg/day 400mg Lopinavir + 100mg Ritonavir. Liver function tests.ml oral solution. Amprenavir Agenerase 50. Routine blood chemistry and complete blood count periodically during therapy. Routine blood chemistry. Liver function tests Renal function tests. Dose escalation required to improve tolerability: 200mg OD for 14 days: then 200mg BD from day 15 onwards 400mg BD Delarvidine Rescriptor 100. (NA) BID As for Ritonavir To be taken with food: moderate fat meal increased bioavailability. With or without meals but not with a high fat meal since this decreased bioavailability. 3) Non−Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Drug (NNRTI) Efavirenz Stocrin 200mg capsules − (A) 50. 100mg capsules 15mg.3mg Lopinavir 4−33. (NA) >50kg: 1200mg BID capsules 1400mg BID oral solution <50kg: 20mg/kg BD capsules Maximum 2400mg/day >50kg: 1.lipid abnormalities. Possible increased bleeding episodes in patient with hemophilia. BID Hepatic renal/function. diarrhea Rash parenthesis Fat redistribution and lipid abnormalities Hyperglycemia Possible increased bleeding episodes in patients with hemophilia. Liver function tests Renal function tests Routine blood chemistry and complete blood count periodically during therapy. Cholesterol levels.

1 hours 3 hours Metabolized to AZT glucoronide (GAZT) Renal excretion of GAZT Renal excretion 50% Renal excretion 70% Renal excretion 50% Renal excretion unchanged Metabolized by alcohol dehydrogenate and glucoronyl transferase.5−2 hours Metabolism Cytochrome P450 3A4 inhibitor (less than Ritonavir) Cytochrome P45U Potent 3A4 inhibitor Cytochrome P450 3A4 inhibitor (less than Ritonavir) Cytochrome P450 3A4 inhibitor (less than Ritonavir) Cytochrome P450 3A4 inhibitor (less than Ritonavir) 30−40% 85% 86% 86% 83% 1. soft gel formulation (Fortovase) Amprenavir (Agenerase) Lopinavir + Ritonavir (Kelatra) 4% but is erratic 1−2 hours Not determined 1−2 hours Not determined Not determined 7.6 hours Cytochrome P450 3A4 inhibitor 5−6 hours Cytochrome P450 3A4 inhibitor CHAPTER FOUR: GUIDELINES FOR THE USE OF ANTIRETROVIRAL DRUGS IN PAEDIATRIC HIV INFECTION 21 . Metabolized by cytochrome P450 (3A mixed inducer/ inhibitor). Data not available 40−55 hours Data not available Drug Indinavir (Crixivan) Oral Bioavailability 65% Ritonavir (Norvir) Nelfinavir (Viracept) Not determined 20−80% 3−5 hours 3.0 hours 3−6 hours 1.3 hours >90% 25−30 hours Data not available Efavirenz Stocrin.5 hours 12 hours 3. 14−34% excreted in urine (glucoronidated metabolites.5−5 hours Saquinavir.Zidovudine (AZT.6 hours 1. Renal excretion of metabolites 82% Metabolized by cytochrome P450 (3A inducer). <1% unchanged). <5% unchanged). Stavudine (d4T) Zerit Lamivudine (3TC) Epivir Abacavir (ABC) Ziagen Nevirapine Viramune 60% 1. Serum Half−life 1. hard gel formulation (Invirase) Saquinavir.5 hours 25−40 hours 3 hours 3. ZDV) Retrovir Didanosine (ddl) Videx Zalcitabine (ddc) Hivid.2 hours 1. 16−61 % in faeces.1−10. 80% excreted in urine (glucoronidated metabolites. 10% in faeces.

Specific guidelines for initiating therapy are: • Symptomatic HIV disease • Development of clinical symptoms • Moderate and Severe immune suppression • High HIV RNA levels (> 10. In children due to the presence of maternal antibodies a definitive diagnosis of HIV infection can only be made at or after the age of 1 8 months.3 When to initiate treatment Antiretroviral therapy is indicated for any child with definitive diagnosis of HIV infection who has evidence of significant immune suppression and/or who has HIV associated clinical symptoms regardless of the age or viral load. The' current Ministry of Health guidelines for HIV diagnosis is a concordant positive result using 2 different ELISA kits.000 copies/ml) • Asymptomatic disease in a 30 month old infact with HIV RNA copy number of > 10. By the end of the 2nd week of life a definitive diagnosis can be made in 93% of infected children.000 copies/ml • Increasing HIV RNA copy number as follows: − A fivefold increase for children aged < 2 years and a > 3 fold increase for children aged > 2 years. There are marked age dependent differences in the profile of T lymphocyte subsets in children. In this context HIV infection is diagnosed by 2 positive HIV virologic tests performed on separate blood samples. Regarding the use of viral load to guide therapy it is worth noting that perinatally infected infants have high plasma viral loads within the first 2 months of life. Diagnosis of HIV infection− is therefore dependent on the use of antibody based tests. the CD4 percentage specifying immune suppression does not change with age and is therefore a more useful marker for identifying disease progression in children. Treatment guidelines for children will therefore have to take these differences into account although they follow the same principles as in adults. 4.) 4. The level of HIV RNA considered indicative of increased risk for disease progression is not well defined for young children and will have to be reviewed as more data becomes available. CD4 cell counts are generally higher than adult levels and attain adult levels by the age of 6 years.4. Infants with CD4 percentage of 15−25% are considered moderately immune suppressed and those with percentage CD4 levels < 15% are considered severely immune suppressed. (In the event that viral diagnostics become widely available then a definitive diagnosis can. Unlike the absolute CD4 cell counts where the levels specifying immune suppression changes with age. be made within 48 hours of birth in 38% of infants. This is followed by a slow decline in the first few years of live. In infancy.1 Overview HIV infection in children is predominantly acquired perinatally and differs from disease in adults in its clinical presentation and disease progression. 22 .2 Diagnosis of HIV infection in children Inmost settings in Kenya viral diagnostic assays are not available.

Can be taken with or without food. 3TC Epivir solution 4mg/kg twice daily for children aged 3 months to 16 years. The solution is stable for 30 days. immunologic or virologic status. Maximum dose should not exceed 600mg/day 1 mg/kg every 12 hours for patients less than 30kg: 30mg twice daily for patients between 30−59kg: 40mg twice daily for patients over 60kg.m2/day). ddl. Oral solution (made from powder) should be refrigerated (2−80°c) after reconstitution. ZDV. Store at 15−250°c. Treatment − 180Mg/M2 every six hours (total 720mg. d4T Zerit pediatric 1 mg/ml (A) Dose Dose for prophylaxis (full term new born): 2mg/kg orally every six hours starting within 12 hours of birth and continuing for 6 weeks. Discard 30 days after reconstitution.6 Dosages for paediatric formulations Paediatric formulations and dosages Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Drug Zidovudine. 120mg/m2 every 12 hours Special precautions Strawberry flavoured syrup.5 Agents to choose for initial treatment As in adults use Paediatric formulations where available. 10mg/ml(NA) Lamivudine.• All children diagnosed as HIV infected within the first year of life regardless of clinical. This is an oral solution made from Shake well before use and keep refrigerated (2080c).4 Initiation of treatment Age Asymptomatic Symptomatic CD4 percentage <25% Treat Treat Treat HIV RNA levels >10. shake well before use. 4.000c/ml Treat Treat Treat <12 months ? 30 months 0−12 years Treat − − Treat Treat Treat 4. 23 . The oral solution can be stored between The oral solution can be stored between 2−30°c. AZT Retrovir pediatric suspension. 4.000c/ml Treat Treat Treat HIV RNA levels > 100. Take > 30 minutes before or 2 hours after eating. pediatric Videx powder. 50mg/5ml (A) Stavudine. 10mg/ml(A) Daily maximum dose is 300mg/day.

Thereafter. weighing > 10kg and who can swallow hard capsules. Maximum recommended dose: 400mg/day. 200mg capsules. 100. Pediatric Norvir Initial dose 250Mg/M2 every 1 2 hours. The oral solution Oral solution should be stored between 2 and 30°c. Children > 8 years: 4mg/kg twice a day. milk formula. Ritonavir. (A) Dose 30−30mg/kg three times daily for children aged 2−13 years. (A) 20mg once a day (10 to < 15kg) 250mg once a day (15 to <20kg) 300mg once a day (20 to <25kg) 350mg once a day (25 to 32. Protease Inhibitors (Pis) Drug Nelfinavir. maintenance dose: Children > 2 months to <8 years: 7mg/kg twice a day. 50mg per 19 scoop. Store at 20−250°c. Indicated for children aged 3 years and above. 4mg/kg once a day for 14 days. Pediatric Viracept powder. Stocrin 50. Ziagen 20mg/ml (NA) 8mg/kg twice a day for children aged > months to 16 years. It can be taken with a meal or light snack and should be taken 1 hour after or more than 2 hours before ddl. It has a bitter taste I reconstituted with acidic food/juice. NON−NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS) Efavirenz. Can be taken with or without food. The powder may be reconstituted with water.Abacavir. Maximum dose is 600mg/day. increased by 24 . soy milk or dietary supplements. Can be taken with or without food. Viramune pediatric 10mg/ml.5kg) 400mg once a day (32.5 to >40kg) 600mg once a day (>40kg) Nevirapine. Special Precautions The oral solution is made from the powder is Stable for upto 6 hours after reconstitution. soy formula.

The maximum daily dose of Amprenavir oral solution is 2800mg. (NA) 4. 4. Amprenavir oral solution and capsules should be stored at room temperature and neither solution nor the capsules should be refrigerated. Amprenavir. the highest tolerated dose should be used. Amprenavir capsules and oral solution are NOT bioequivalent. should not be refrigerated but stored at 20−25°C. 50. ii) Repeated detection of HIV RNA in children who were initially undetectable. Immunologic considerations i) Change in immune classification (e. Oral capsules: for patients between 4−12 years of age or for patients 13 to 16 years of age who weigh less than 50kg. but should not be taken with a high fat meal. the recommended dose or oral solution is 22mg/kg twice daily or 17mg three times daily.9 When to change therapy Virologic considerations i) Inadequate virologic response after 8−12 weeks of therapy Le. Efficacy and safety of Amprenavir have not been established in patients younger than 4 years of age. 25 . Clinical considerations i) Progressive neurodevelopment deterioration. Agenerase. a persistent decline of 5 percentiles or more. and thus are not interchangeable on a milligram per milligram basis. NB: Capsules and oral solution are not interchangeable on a milligram per milligram basis. Once maximal suppression of HIV RNA levels is achieved then levels should be measured every 3 months to evaluate continued response to therapy. For adolescents 13−16 years of age who weigh 50kg or more the recommended dose is 1200mg twice daily.8 Monitoring Virologic response should be assessed 4 weeks after initiating therapy.< 10 fold reduction from baseline levels in children receiving "NRTIs and PI or <5 fold reduction from baseline in children receiving "NRTIs. Oral solution: for patients between 4−12 years of age or for patients 13 to 16 years of age who weigh less than 50kg.g.syrup 80mg/ml 50mg/m2 at 2−3 day intervals to 400mg/m2 twice daily (recommended dose). from moderate to severe immune suppression) ii) For patients with severe immune suppression (CD4 levels <15%). 100mg capsules Oral solution: 15mg/ml. >30% decline in <6 months. iii) A greater than 3 fold increase in viral copy number in infants <2 years. Shake well before use. iii) A rapid and substantial decrease in CD4 counts i. The maximum daily dose is 2400mg. the recommended dose is 20mg/kg twice daily or 15mg/kg three times daily. Amprenavir may be taken with or without food. iv) A greater than 3 fold increase in viral copy number in infants>2 years. If 400mg/m2 is not tolerated. Maximum dose: 600mg twice daily.e.

5. There are measures which can be put in place in the management of expectant mothers so as to reduce the rate of transmission of HIV from an infected mother to the baby. Upto 90% of HIV infection in pregnant women is due to heterosexual contact. table 5. Smoking. a seroprevalence rate of 20% in mothers. Decrease in the number of HIV infected orphans. expand health services and strengthen health infrastructure. Multiple sexual partners. and an MTCT rate of 40%. This is a big number that the country will find difficult to cope with. and breastfeeding (40 − 50%). In 1 999. Injection drug abuse. a birth rate of 1. MATERNAL 26 .1 summaries factors affecting mother to child transmission of HIV infection. out of which 90% of the HIV infection was due to MTCT With our population estimated at 28. labour and delivery (35 − 50%).2 Factors affecting mother to child transmission a) According to the current state of knowledge.ii) Growth failure. In order to reduce MTCT these areas must be targeted. CHAPTER FIVE: MANAGEMENT OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTED PREGNANT WOMEN AND PREVENTION OF MOTHER TO CHILD TRANSMISSION (MTCT) OF HIV 5.1 FACTORS AFFECTING MTCT Category VIRAL Strong evidence High viral load Viral genotype and Phenotype Advanced disease (immune deficiency) HIV infection acquired during pregnancy or breast−feeding period. With reduction of MTCT. the following benefits will be derived: Increase in child health and survival. With the observed trends. the percentage of pregnant women who are HIV infected is increasing at an alarming rate. In order to achieve these set goals collaboration between health care providers and other significant stake holders must be put in place.000. Opportunity to improve. anemia Sexually Transmitted Diseases/ Chorioamnionities. 1 0% of reported AIDS cases in children were under 5 years of age. Limited evidence Viral resistance (theoretical possibility) Vitamin A deficiency. Frequent unprotected Sexual intercourse. the expected number of HIV infected infants per annum in Kenya will be approximately 100. Transmission of HIV from infected mothers to their babies can occur during the antenatal period (10 −20%).2 million. antiretroviral therapy and modification of obstetric practices and replacement feeding for the baby.1 Overview The seroprevalence rate of HIV among pregnant women in Africa exceeds 20% in many areas. These measures include voluntary counseling and testing (VCT).2 million per annum. TABLE 5. In Kenya HIV prevalence in urban sentinel sites in 1998 among pregnant women was reported to range between 4 − 10% in low seroprevalence sites to 20 − 35% in high seroprevalence sites.

treatment and prophylaxis. its use in our setup is debatable. oral thrush) FOETAL/INFANT BREAST−FEEDING Duration.OBSTETRICAL Vaginal delivery (compared to elective Caesarian section).3 Outline antenatal. VCT. Treatment of STI Usual ANC.g. Pneumonia Treatment Usual ANC care. selective use of episiotomy and sucking of the oral pharynx of the baby while vaginal cleaning with hibitane (chlorhexidine 0. Kaposis sarcoma. Treatment o STI. 27 . As shown in table 5. Elective caesarian section reduces the risk of MTCT of HIV infection as shown in table 5. breast disease (mastitis/ cracked nipple). Rupture of the membranes for more than 4 hours. labor and delivery and the postpartum period includes intensive counseling and voluntary testing (both pre− and post−). a) The antenatal care of a women identified to be HIV positive is summarized in table 5.25%) solutions may reduce the risk of puerperal and neonatal sepsis. Prematurity Invasive procedure: instrumental deliveries. Some of these practices include avoiding early rupture of membranes during labor.g. At the same time. Usual ANC. proper management of labor using the partogram consistently will reduce the risk of prolonged labor in all women while avoiding invasive procedures. VCT MTCT−AZT. c) Postpartum and postnatal care Practices toward reduction of MTCT during the postpartum and postnatal period involve appropriate maternal care and breast care to avoid cracked nipples and mastitis. b) Factors known to reduce MTCT Elective caesarian section: Non−breast−feeding: Antiretroviral therapy Knowledge of the above should form the basis for providing care to mothers and their babies. Overall half of the breast milk transmission takes place by 6 weeks. external cephalic version (ECV). episiotomy. some practices may increase the risk of HIV transmission to the baby having little or no proven obstetric value. CNS manifestations.1. screening/obstetric interventions. MTCT−AZT. Multivitamin. Nutritional support. However. MTCM−AZT. Treatment of specific infections. Military TB. amniocentesis. b) Intrapartum care Due to the HIV/AIDS Pandemic. lesions or the skin/or mucous membranes (e. Specific treatment of opportunistic infections. VCT. 5. e. Genetic.2 Category HIV seropositive HIV− infected with opportunistic infections Immune − suppression Diseases Well and Asymptomatic e.g. laboratory investigations. adequate and timely counseling regarding contraception and breast feeding should have been part of the care all through pregnancy and continued during the postpartum and postnatal periods.1. modification of routine care during the Intrapartum period is necessary. intrapartum postpartum and postnatal care The care of HIV infected women during antenatal period. mixed feeding. Ideally. Intrapartum hemorrhage. and three quarters by 6 months after delivery.

it is advisable to start treatment at 34 weeks gestation since most of our patients deliver before 40 weeks gestation and they would not have had optimum therapy. animal studies are either positive for foetal risk. CHAPTER SIX: SPECIAL CONSIDERATIONS 6.1 Acute retroviral syndrome (ARVS) At least 60% of patients acutely infected with HIV will experience at least some symptoms of the acute retroviral syndrome. however various regimes of ARV therapy currently favored and available for prevention of mother to child transmission of HIV infection as shown in table 5. then 1 mg/kg/hr 300mg p.3 ANTI−RETROVIRAL THERAPY FOR REDUCTION/PREVENTION OF MCT Breast Feeding Status Non breast feeding Non breast feeding Breast feeding Drug ANC Labour Baby % Reduction of MTCT 68% (infection) status at 18 months) 50% (infection status at 6 months age) 47% (infection status at 6 weeks age) ZIDOVUDINE 100mg p.o. 3hrly 2mg/kg p. 6hrly x 6 wks No 200mg single dose at the onset of labour 2mg/kg single dose in the first 72 hours In our Kenyan set up. TABLE 5. labor. Symptoms one could look for include: Fever (96%) Lymphadenopathy (74%) Pharyngitis (70%) Rash (70%) 28 .o. It is still controversial whether there are any benefits of antiretroviral therapy at this early stage.d.4 Antiretroviral Therapy to prevent MTCT The safety of most antiretroviral agents to the foetus and infant has not been established thus narrowing the choice of ARV drug therapy to prevent MTCT during pregnancy. Physicians should maintain a high level of suspicion especially where there are known or established recent high risk factors. delivery and the postpartum/postnatal/ Infant periods. Details of further regimes recommended in preventing MTCT are provided in Appendix XT 11. are in class "C" in which safety in human pregnancy has not been determined.V 2. NEVIRAPINE No 1.3.0mg/kg st. and the drug should not be used unless the potential benefit outweighs the potential risk to the foetus". or have not been conducted. 5 times daily from 14−34 wk gest. if one is to use The Thai Regime. According to the 'American FDA Pregnancy Categories". Acute HIV infection is often not recognized in the primary care setting because of the similarity of the symptoms with those of other common diseases or flu. ZIDOVUDINE 300mg p. if the therapy is started at 36 weeks. There are. from 36−40 from gest.o o. but most clinicians would offer treatment during this acute attack. Zidovudine (ZDC) and Nevirapine (NVP).5.o.

In this period. The use of Rifampicin to treat active TB is specifically contraindicated for patients taking any of the Pis or NNRTIS. oesophagus or genitals.Erythematous maculopapular rash with lesions on face and trunk and sometimes extremities including palm and soles. 29 . Kaposi Sarcoma. Mucocutaneous ulceration involving mouth. Rifabutin originally recommended for use is too expensive and toxic.3 Immune recovery syndrome Initiation of potent antiretroviral therapy is associated with recovery of immune function. patients with advanced disease could present with skin rash. New data indicate that Rifampicin can be used for the treatment of active TB in situations where the patient is taking NNRTI (Efavirenz) and two NRTI. or PI (Ritonavir) and one or more NNRTIS or a combination of two PI (Ritonavir and Saquanavir). mucocutaneous. This is not drug failure and the treatment should be continued.2 ARV drugs and the treatment of Tuberculosis Several anti−tuberculosis regimes can be administered with effective antiretroviral therapy in HIV infected person.g. lymphademopathy. 6. Myalgia or arthralgia (54%) Diarrhea (32%) Headache (32%) Nausea and vomiting (27%) hepatosplenornegaly (14%) Weight loss (13%) Thrush (12%) Neurologic symptoms (12%) Meningoencephalitis or aseptic meningitis Peripheral neuropathy or radiculopathy Facial palsy Guillain−Barre syndrome Brachial neuritis Cognitive impairment or psychosis 6. ulceration and immunological response to subclinical opportunistic infection e. and drugs regimens that include Rifabutin were suggested as preferable alternatives. and tuberculosis. Steroids could be administered in some of these cases and careful use of antihistamines.

Side Effects Initiation of STI to control or prevent some long−term toxicities associated with HAART therapy might be useful. Pregnancy Although antiretroviral therapy has shown considerable benefits in reducing perinatal HIV transmission rates.1 Structured treatment interruptions (STI's) With the growing number of drawbacks and uncertainties with long term antiretroviral therapy. Adherence Poor adherence had been identified as a leading cause of drug failure in patients receiving antiretroviral therapy. the patient should be monitored by clinical. Stopping therapy in these patients. Before initiating Structured Treatment Interruptions.CHAPTER SEVEN: WHEN TO STOP TREATMENT (INTERRUPTIONS) 7. However. Restart therapy if there is viral rebound of 0.8 + I load and a significant decrease in CD4 + count. STI although a new concept holds a great promise in the future management of HIV/AIDS. carried through to the second trimester when such side effects are less common. Patients with multiple−drug resistance and experiencing treatment failure In patients who have multiple drug resistance. which confer−drug resistance and in many cases allow for a shift to drugsensitive wild−type virus. viral load below 50/mml for at least a period of one year. There is not enough data to support the fact that the temporary cessation of therapy has any significant impact on side effects such as elevated liver function or peripheral neuropathy or nutritional disorders. scant data are available to indicate that antiretrovirals are safe for a developing foetus during the first trimester of pregnancy when teratogenicity is most common. Boosting HIV specific cellular responses Hypothesis that STIs might induce HIV specific immune responses synonymous with robust HIV specific CD4+ and CD8 cells responses believed to control veremia in seropositive long−term non−progressors. the viral load and CD4+ and CD8+ values should be monitored on every three monthly intervals. it should come as no surprise that both clinicians and patients are finding optimism in structured treatment and interruptions (STIs). STI is a new concept and new data is needed to be available before it is advocated universally. i. laboratory and surrogate markers as it was done prior to STI. until at least these adherence issues are dealt with may prove to be a short−term preventive solution to a long−term dilemma of multiple drug resistance. STIs have been suggested as an option. 30 . stopping treatment will be a feasible option for HIV infected women receiving HAART prior to pregnancy. Successful HAART appears to be associated with decreased HIV specific cellular immunity to the virus as a result of limited antigen stimulation just enough to challenge the immune system without overdoing it ultimately leading to the HIV specific CD4+ and CID8 cells. Various rationales for stopping treatment in HIV infected patients for short periods of time have been hypothesized. In such cases.e. STIs in treatment failure will halt the evolution of additional mutations. On the commencement of therapy. On commencing STI. a patient should have immune reconstitution within acceptance limits.

8. 4) The provision of written information to provide support outside the clinic setting.2 Non structured treatment interruption All patients on antiRetroviral Therapy need to be fully committed to the regimes prescribed. CHAPTER EIGHT: GUIDELINES FOR POST EXPOSURE PROPHYLAXIS The following actions should be taken immediately following possible exposure to HIV 8. 2) The impact of therapy on an individual s life−style and psychology. When initiating therapy. the following should be considered at least: 1 ) The motivation of an individual to begin and continue therapy. Thus for the majority of individuals continuation of therapy is associated with better prognosis than discontinuation. Results from structured treatment interruptions trials are still awaited. 31 . • Injury with a hollow needle. perhaps using memory aids. • Exposure to blood or blood contaminated fluids from a patient with a high viral titre like in clinical AIDS phase or early seroconversion phase of HIV.1 Treatment of exposure sites Wounds and skin sites should be washed with soap and water.3 Assessment of exposure risk Low risk exposure is • Exposure to a small volume of blood or blood contaminated with fluids from asymptomatic HIV positive patients with low viral titre. Many individuals stop treatment on their own due to various factors which include financial reasons.7. Mucous membranes should be flushed thoroughly with water. • Following an injury with a solid needle. Most drug therapy discontinuation have been associated with a rapid rise in viral load and a fall in CD4 cell count. 3) The potential risks and benefits of therapy in the short and long term. High risk exposure • Exposure to a large volume of blood or potentially infectious fluids. including the need to establish and maintain a pill−taking routine. psychological problems and other issues.2 Timing of post − HIV exposure prophylaxis initiation Therapy should be initiated within 1 − 2 hour of exposure. 8. drug toxicities. • Any superficial injury or mucocutaneous exposure.

Retrovir 200 mg tds (300 mg bd) + Epivir 150 mg bd + Indinavir 800 mg tds Or. • Splashing of such contaminated blood and body fluids to muco cutaneous membranes (eyes. or with intact skin for duration's in excess of 3 minutes and over extensive body surface area. • Confirmed drug resistance in source patient. Duration 28 days 28 days 8. CSF. secretions from the genital tract) from HIV infected person through any of the following ways: • Pricks by contaminated solid and hollow needles. peritoneal fluid. 32 .4 Post − HIV exposure prophylaxis Risk category Low risk High risk ARV prophylaxis Retrovir 200 mg tds (300 mg bd) Epivir 150 mg be or combivir 1 bd. Combivir 1 bd + Indinavir 80 Otds.• Deep and extensive injuries.5 Recommended HIV serology after exposure Time period from exposure Baseline − − − − Two weeks − − Six weeks Three weeks Six months − − − Recommended tests Full blood count Liver and renal function tests HIV Serology Full blood counts Liver and renal function tests HIV Serology HIV Serology HIV Serology * Please note that non−protective casual sex is considered to be a HIGH RISK EXPOSURE 8. mouth and nose). 8.6 Management of health care workers with accidental exposure to HIV infection 1) Introduction A Health Care Worker (HCW) becomes exposed to HIV infection When he/she comes in contact with blood or body fluids (amniotic fluid. • Pricks and cuts by contaminated sharps Contact of such contaminated blood and body fluids with non intact skin.

then he/she should not be commenced on any antiretroviral chemoprophylaxis. should be further counselled.The term source person is use in rerence to the person whose blood or body fluids the HCW becomes exposed. source person. 4) Pretest Counselling The following pertinent points should be part of the contents of the pre−test counselling of the affected HCW. is done. the attending Medical officer should contact the consultant in charge or any other senior Administrator who should have over−riding powers to authorise HIV testing in such cases. − The source person is confused or in coma. address. a start dose of combivir should be given then the rest of the management of the HCW continued after the emergency care referred to above. If the result is positive. the affected HCW should present herself/himself to a Medical Officer who should ensure the following: The necessary documentation including names of HCW. no anti−retroviral chemoprophylaxis needs to be recommended. time of incident. a start dose of combivir should be given to the HCW. Should the result be negative. size of exposure etc. the HCW should be further counselled and if he/she still objects to being HIV tested. if antiretroviral 33 . the attending Medical Officer should ensure the following: − The consultant in charge or a Senior Administrator is informed. − If the source person turns out to be HIV positive. These powers could be exercised where: − The source person objects to being HIV tested. If the spot test is not available. 3) After receiving the immediate care. • That the testing has significance beyond a mere offering of epidemiological data.03% (CDC statistics). In the event of the HCW objecting to being HIV tested. Evaluation of the risk category (in terms of high or low) of the affected HCW and making a decision to recommend or not to recommend anteretroviral chemoprophylaxis should be done urgently.3% and muco−cutaneous exposure to blood is approximately 0. Incase the source person is unwilling to be HIV tested. • That the possible chances of infection from the accidental exposure (percutaneous inoculation from HIV positive source person) is approximately 0. − The case of a minor where a guardian or parent is not available. • That the testing is done under confidential status. − The HCW is aware that Hospital may not take responsibilities for any eventuality arising out of that accidental exposure. − The source person should still be HIV tested but no antiretroviral chemoprophylaxis recommended for the HCW who instead. 2) HIV spot test should be performed on the source person. • That antiretroviral chemoprohylaxis is beneficial. • That failure to take the HIV test by the affected HCW will negatively affect any future proceedings which require proper documentation.

The majority of cases that fall under this category comprise victims of rape or consensual casual sex partners who have suffered burst condoms. Inform the senior member of staff in−charge immediately who will confirm that the above have been followed. Note: Do not scrub the area or use a nail brush. 6. − The degree of injury: Multiple injuries or deep and extensive injuries carry a higher risk of infection in addition to those listed earlier. • Non−sexual non−occupational exposure to HIV occurs when a victim comes in contact with blood or body fluids from an infected person through any of the following ways: 34 .chemoprophylaxis is recommended. 8. mucus membrane or non−intact skin. Methylated spirit or other verucidal disinfectant (Optional). Recommendations to be taken in case of accidental sharps injury or exposure to blood or body fluids are as follows: 1. Cover with waterproof dressing if appropriate. Encourage bleeding by squeezing site if a puncture wound.8 Management of non occupational exposure to HIV infection I. 3. There are certain factors which increase the risk of transmission of HIV. Terminal AIDS persons have a higher viral load. Definitions Non occupational exposures to HIV can be grouped into two broad categories: Sexual exposures and non−sexual exposures.7 Management of hospital staff with sharp injury or exposure to blood and body fluids Introduction Members of the health professions and para−medical staff who are in contact with patients and or clinical materials are at a continuous risk of infection with HIV from accidental sharps injury or exposure to body fluids. peno−anal and peno−oral). 2. The chemoprophylaxis should be discontinued once the source person turns out to be HIV NEGATIVE or HCW turns out to be HIV POSITIVE from baseline tests. 5. 4. 8. Irrigate with water if splashing occurs into eye. Apply Betadine. Iodine. some of which are as follows: − The stage of infection of the source person. The patient will then be referred for treatment as earlier indicated. These two categories exclude perinatal exposure • A person becomes sexually exposed to HIV when he/she comes in contact with secretions from an HIV infected sexual partner/assailant through a discrete penetrative sex act (peno−vaginal. Do not suck out blood. Wash the affected area gently with plenty of soap and water. it should be initiated as soon as possible preferably within an hour post exposure.

Pre−test counselling the victim and obtaining of informed consent for HIV testing.g. the medical officer should determine the number of persons sharing the injection device and the length of time the victim has been on the method. all HIV seronegative rape victims should be recommended for antiretroviral chemo−prophylaxis. Such laboratory specimens include HVS for MCS. visible an−genital ulcers and inflammations). Apart from when the assailant is know to be HIV seronegative. VDRL and HbsAg. Hepatitis B. The place and time the exposure took place. only those who come after two weeks of exposure should be disqualified from receiving antiretroviral chemoprophylaxis on account of lateness. they should be "followed up in the appropriate clinics. Other factors that increase risk of transmission include: victim with STD and no−genital ulcers. PDT. douche). 3. There is hardly any benefit in recommending antiretroviral chemophylaxis for those who expose themselves to HIV through injecting−drug use unless they are willing to 35 .g. (The risk of HIV transmission per episode of IV needle exposure is estimated at 0. the identity of the informant and also that of the assailant (if possible) should be recorded. If the exposure is of the injecting−drug use type. RTAs and other mass accidents (e. bomb blasts. although the efficacy of antiretroviral chemoprophylaxis has been proven (mostly in animal studies) to be optimal when it is commenced early within a few hours of exposure. non−intact skin or with intact skin for prolonged periods (in excess of 3 minutes) and over extensive body surface. Management of sexual exposures to HIV: Identification data of the victim which should include the victim's marital status. train and air traffic crashes. 1. multiple assailants and assailants with unknown HIV status lifestyles). nature of the exposure. However. whether victim was already pregnant or already had STD infections at the time of the exposure). mass shootings. vaginal or anal tears) and determination of factors that could affect the degree of the risk of HIV transmission (e.9 Management of non−sexual and non occupational Exposures to HIV Recording of the victims identification data. multiple assaults with a common weapon and certain practices such as traditional circumcision. where a common needle/sharp is used. This often happens to participants in rescue mission at traffic and sports accidents and also at obstetric emergencies that occur in public places. the length of time which has elapsed from the exposure to the moment the victim presented for medical care and making of the decision to recommend or not to recommend antiretroviral chemoprophylaxis. whether penetration and ejaculation was achieved and what the victim did immediately after the exposure in order to minimize the risk (e.67%). Hepatitis C) should be taken along side that for HIV). 1 % to 0. 2. Evaluation of the sexual exposure in terms of the number of assailants involved. Taking specimens for laboratory analysis for use in verification of exposure and determination of conditions that may modify other consequences of the exposure (e. 4. Pre−test counselling and obtaining of informed consent for HIV testing. Blood− samples or other diseases which could be transmitted through the same exposure (such as syphilis. 6. (The risk of HIV transmission per episode for receptive peno−anal sexual exposure is estimated at 0. the number of children the victim has.Pricks and cuts by needles and sharps through such means as injectingdrug−use. Determination of the risk category. Victims with a low exposure risk and those who come too late after the exposure need not to be recommended for antiretroviral chemoprophylaxis. semen on the victims underwear. Determination of evidences of the exposure (e. 5. place and time the exposure took place. shaving and tattooing. Contact of such contaminated blood and body fluids with mucous membranes.g. record of any contraceptives currently being used and LMP for female victims. 8. the identity of the informant and the time the victim presented for medical care.2%. urine for MCS.g.g.

The computed risk of HIV transmission (computed for available data on the local HIV prevalence multiplied by the number of RTA victims assisted) should also be disclosed to the patient. No change in rifabutin AUC Avoid concomitant use.be rehabilitated through counselling and psychiatric care aimed at weaning them from their dangerous habit. in particular training of physicians involved in monitoring ARV therapy is crucial to ensure quality services. A good infrastructure for the provision of ARV therapy. Levels: APV AUC decreases 15% Rifabutin increases 193% Dose: No Lopinavir (LPV) Levels: LPV AUC decreases 13% Keto increases 3−fold. CHAPTER NINE: ACCESS TO DRUGS IN KENYA The lack of accessibility to ARV drugs by the majority of Kenyans remains a major obstacle to HIV/AIDS patients. Levels: Rifabutin AUC increases 3−fold. The Ministry of Health will take the lead in these scale−up activities and ensure that affordable quality ARV drugs are accessible to all Kenyans. The main barriers to providing ARV therapy in Kenya as in many other developing countries is the cost of drugs themselves. The recent legislative amendments by the Government of Kenya is aimed at enhancing ARV access to the majority of the HIV/AIDS patients The dramatic price reductions witnessed recently offers hope that ARV drugs will soon be available. Facilities for ARV therapy currently focused in urban health institutions with better− infrastructure will need gradual scale−up to the other parts of the country. Drug to drug interactions Drugs Affected ANTIFUNGALS Ketoconazole ANTI−MYCOBACTERIALS Rifabutin Amprenavir (APV) Levels: APV increases 31% 3X Ketor reduces 44% Levels: APV AUC decreases 82%. Nelfinavir (NFV) No dose adjustment necessary Levels: LPV AUC Level: 82% decreases 75% Contraindicated Avoid concomitant use. Those who get exposed to HIV through RTAs and other mass accidents where multiple exposure to blood and body fluids of other victims of the same accident can not be ruled out. These guidelines will become useful to prescribers and other Health workers. should be recommended for Antiretroviral chemoprophylaxis. The chemoprophylaxis should be taken for a period of 28 days. The standard care in ARV therapy requires viral load monitoring and CD4 cell counts. APPENDICES I. Access to ARV therapy is restricted currently to major hospitals and big urban health institutions. Both of these are expensive and available in only limited institutions within the country. Decrease Rifabutin Levels: NFV 32% Rifabutin increases 2X Rifabutin 36 . factors which hinder access to a bigger portion of the population.

then use rifampin 600 mg qd or 2−3x per week Level: 82% Contraindicated Saquinavir (SQV) Levels: SQV 3x Dose: Standard Nelfinavir (NFV) No dose adjustment necessary Level: IDV 68% Dose: IDV 600 mg tid ANTI−MYCOBACTERIALS Rifabutin Level: IDV 89% Contraindicated Rifabutin Level: IDV 32% Rifabutin 2X Levels: 4X Dose: Rifabutin to Level: SQV 40% No dose adjustment unless Levels: NFV 32% Rifabutin 2X 37 . Levels: Potential for large increase in statin levels. Drug to drug interactions (continued) Drugs Affected ANTIFUNGALS Ketoconazole Indinavir (IDV) Ritonavir (TRV) Levels: Ketoconazole 3X Dose: Use with caution. ANTICONVULSANTS Phenobarbitol Phenytoin Carbamazephine Unknown but may decrease APV levels substantially Monitor anticonvulsant level.change in APV dose Decrease Rifabutin to 150mg qds or 300mg 2−3x/week dose to 150mg gds Dose: Increase Rifabutin to 150mg qd Decrease NFV dose to 1000 mg tid. LIPID LOWERING AGENTS Simvastatin Lovastatin Levels: Potential for large increase in statin levels. do not exceed 200mg Ketoconazole daily Levels: 35% Dose: No Data Increased liver toxicity possible Level: SQV 84% Contraindicated. II. No change in clarithromycin AUC No dose adjustment Levels: Potential for metabolic interactions use alternative or additional methods Levels: Ethinylestradiol decreases 42% Use alternative or additional methods. Avoid concomitant use Unknown but may decrease LPV levels substantially Monitor anticonvulsant level. Avoid concomitant use Levels: Potential for large increase in statin levels. Avoid concomitant use Unknown but may decrease NFV levels substantially Monitor anticonvulsant level. unless using RTV+SQV. No data Clarithromycin Levels: APV AUC increase No data 18%. ORAL CONTRACEPTIVES Levels: Norethindrone 18% Ethinylestradiol 47% Use alternative or additional method.

Consider alternative agent. Avoid concomitant use Unknown Use with caution Monitor anticonvulsant level Theophylline decreases 47% monitor theo levels. Drug Interactions Between Antiretrovirals and Other Drugs Non−Nucleoside Reversed Transcriptase Inhibitors (NNRTIs) Drugs Affected ANTIFUNGALS Ketoconazole Levels: Keto. 77% Dose adjusted for renal insufficiency Levels: Ethinylestradiol 40%. Use alternative or additional methods SQV 177% No dose adjustment. Levels: Potential for large increase in statin levels. No data No data Levels: Norethindrone 18% Ethinylestradiol 47% Use alternative or additional method Levels: Potential for large increase in statin levels. Avoid concomitant use Unknown but may decrease NFV Level substantially Monitor anti convulsant level.Dose: Rifabutin to 150mg qd. 45% Level: Clari.63% NVP 15−30% Dose: Not recommended No data Nevirapine (NVP) Delavirdine (DLV) Efavirenz (EFV) No data ANTI−MYCOBACTERIALS 38 . Grapefruit juice decreases IDV levels by 26% 150 mg qds or dose 3x per week RTV: standard using RTV+SQV. Avoid concomitant use Carbamazephine markedly decreases IDV AUC. Dexamethasone decreases SQV levels. or 300mg 203x /week IDV 1000mg tid Clarithromycin Level: Clari. Levels: Clari. Levels: Potential for large increase in statin levels. 53% No dose adjustment ORAL CONTRACEPTIVE Level: Norethindrone 26% Ethinylestradiol 24% No dose adjusted LIPID LOWERING AGENTS Simvastatin Lovastatin Levels: Potential for large increase in statin levels. then use Rifabutin 150mg 2−3x/week Dose: Rifabutin to 150 mg qd NFV does to 1000 mg tid. Avoid concomitant use Unknown but may decrease SQV level substantially Monitor anticonvulsant level Grapefruit juice increases SQV levels. ANTICONVULSANTS Phenobarbitol Phenytoin Carbamazephine Miscellaneous III.

LIPID LOWERING AGENTS Simvastatin Lovastatin No data Levels: Potential for Large increase in statin levels. No data decreases significantly. Rifabutin 35% Dose: Rifabutin dose to 450 mg qd. No data Unknown but may decrease DLV levels Substantially Monitor anticonvulsant May increase levels of Dapsone. No dose adjustment. Titrate methadone dose to effect. Levels: Methadone IV. DVL 44% Dose adjusted for renal failure No data Level: Ethinylestradiol 37% No data on other component Use alternative or additional methods. Alternative recommended 39% Clari. 100%. Use alternative or additional methods. Do not exceed 25mg in a 48 hour period. Avoid concomitant use. Warfarin and Quinidine Sildenafil: Potential for increased concentrations and adverse effects. Titrate dose to effect. ORAL CONTRACEPTIVES Levels: Ethinylestradiol decreases 20%. Monitor Warfarin when used concomitantly MISCELLANEOUS METHADONE Levels: NVP unchanged. Unknown Use with caution monitor anticonvulsant level. Nucleoside Reverse Transcriptase Inhibitors (NRTIS) Drug Interactions Requiring Dose Modifications or Cautions Use 39 . Levels: Clari. No data ANTICONVULSANTS Phenobarbital Phenytoin Unknown Use with caution monitor anticonvulsant level. Levels: Clari. Clarithromycin Levels: NVP 26%.Rifampin Levels: NVP 37% Not recommended Rifabutin Levels: NVP 16% No data for Rifabutin dose Levels: DVL 80% Rifabutin 100% Not recommended Level: DVL 6% Contraindicated Levels: EFV 25% No dose adjustment Levels: EFV unchanged. Methadone decreases Significantly. 30%.

Saquinavir (SQV) Levels: SQV AUC and Cmin increased Dose: SQV 800mg bid LPV/r standard. Dose: insufficient data Levels: APV AUC and Cmin increased Dose: APV600−750mg bid. No data Miscellaneous Ribavirin inhibits phosphorylations of ZDV. 600mg bid Ritonavir Levels: RTV no effect SQV^ 20X Dose: Invirase or Fortovase 400mg bid + RTV 400mg bid • • Levels: APV AUC^ 2. this combination should be avoided if possible. No data Didanosine (ddl) Levels: ddl 41%. Methadone unchanged. Nelfinavir (NFV) • • Levels: APV AUC^ 1.5−fold.Drugs affected Methadone Zidovudine (ZDV) No data Stavudine (d4T) Levels: d4T 27% Methadone unchanged No dose adjustment.5x Dose: RTV 400mg bid + NFV 500−750 mg bid Levels: SQV^ 3−5x NFV^ 20%+ Dose: Standard NFC Fortovase 800mg tid or 1 200mg bid • Amprenavir Levels: APV AUC^ 33% Dose: No change Dose: IDV Lopinavir/ Ritonavir Levels: IDV AUC And Cmin increased. LPV/r Standard. Amprenavir VI. V. Dose: Limited data APV 600−1200mg bid + RTV 100−200mg bid Levels: APV AUC decreases 32% Dose: insufficient data Lopinavir is Co−formulated with Ritonavir as Keletra. Consider ddl dose increase. Effect of Drug on levels (AUGs)/Dose 40 .5−fold. or IDV 800mg bid + RTV 100 or 200mg bid Saquinavir* Levels: IDV no effect SQV^ 4−7x Dose: Insufficient data Nelfinavir Levels: IDV^ 50% NFV^ 80% Dose: Limited data for IDV 1200mg bid + NFV 1250mg bid Levels: RTV no effect NFV^ 1. Drug Interactions: Protease Inhibitors Effects of Drug on Levels (AUCs)/Dose Drug Affected Indinavir (IDV) Ritonavir Levels: IDV^ 2−5X Dose: IDV 400mg bid. Drug Interactions: Protease Inhibitors and Non−Nucleoside Reverse Transcriptase Inhibitors − Cont.

DLV standard (monitor transaminase levels) Levels: NFV^ 2x DLV decreases 50% Dose: No data (monitor for neutropenic complications) Efavirenz Levels: IDV 31% Dose: IDV 1000mg q8h EFV: standard Levels: RTV^ 18% EFV^ 21% Dose: RTV 600mg bid (500mg bid for intolerance) EFV standard Levels: SQV 62% EFV 12% Co−administration not Recommended Levels: NFV increases 20% Ritonavir Levels: RTV decreases 11 % NVP no effect Dose: Standard Saquinavir (SQV) Levels: SQV decreases 25% NVP no effect Dose: No data Nelfinavir (NFV) Levels: NFV^ 10% NVP no effect Dose: Standard VII. Drug That Should Not be Used With Antiretrovirals Drug Category Ca++ channel blocker Cardiac Lipid Lowering Agents Anti−Myco bacterial Antihistamine Gastrointestinal drugs Nevirapine Delavirdine (None) (None) (None) (None) (None) (None) (None) (None) Simvastatin Lovastatin Rifampin Rifabutin Astemizole Terfenadine Cisapride H−2 blockers Proton pump inhibitors (None) Midazolam Triazolam Efavirenz (None) (None) (None) (None) Astemizole Terfenadine Cisapride Neuroleptic Psychotropic (None) (None) (None) Midazolam Triazolam ** This is likely a class effect.Drug Affected Indinavir (IDV) Nevirapine Levels: IDV decreases 28% NVP no effect Dose: IDV 1000mg q8h NVP: standard Delavirdine Levels: IDV^ >40% DLV no effect Dose: IDV 600mg q8h DLV: standard Levels: RTV^ 70% DLV: no effect Dose: Standard RTV: no data Levels: SQV^ 5x DLV no effect Dose: Fortovase 800mg tid. Suggested Alternatives 41 .

cetirizine Midazolam.Simvastatin. lorazepam. cerivastatin (alternatives should be used with caution) Rifabutin: clarithromycin. fexofenadine. pravastatin. Lovastatin: atorvastatin. Terfenadine: loratidine. Drugs that should not be used with Protease Inhibitors Antiretrovirals Drug Category Amprenavir Ca+ Channel bocker Indinavir Lopinavir+ (None) (None) Cardiac (None) Amiodarone Flecainide Flecainide Propafenone Lipid Lowering Agents Simvastatin Simvastatin Lovastatin Lovastatin Anti−mycobacterial Rifampin Rifampin Antihistamine Astemizole Terfenadine Terfenadine Terfenadine Gastrointestinal Drugs Cisapride Simvastatin Simvastatin Lovastatin Lovastatin (None) Rifampin Astemizole Terfenadine Terfenadine Terfenadine Cisapride Cisapride Neuroleptic (none) (none) Clozapine Pimozide Pimozide Psycotropic Midazolam Midazolam Trizolam Trizolam Ergot Alkaloids Midazolam Midazolam Trizolam Trizolam Midazolam Trizolam Midazolam Midazolam Midazolam Terfenadine Cisapride Cisapride (None) (None) (None) Cisapride Cisapride Lovastatin Rifampin Rifampin Astemizole Astemizole Astemizole Astemizole Lovastatin Rifampin Rifampin Simvastatin Simvastatin Simvastatin (None) (None) Ritonavir* Bepridil Saquinavir (None) Nelfinavir (None) Ritonavir Bepridil Dihydroergotamine Dihydroergotamine Dihydroergotamine Dihydroergotamine Dihydroergotamine Dihydroergotamine Dihydroergotamine 42 . azithromycin (MAI prophylactics). Triazolam: temazepam. fluvastatin. VIII. clarithromycin ethambutol (MAI treatment) Astemizole.

E. 5 times daily starting at 14−34 week gestation. 45) Ergotamine** Ergotamine** (Various forms) (Various forms) (D. then 1 mg/kg/hr POSTPARTUM No INFANT 2mg/kg p.E. 6 hourly for 6 weeks No REDUCTION IN MTCT 68% (infection status at 18 months 50% (infection status at 6 months age) AZT 300mg p. 300 mg p.E. Thus. Anti−retroviral therapy for preventing MTCT STUDY PACTOG 076 Non Breast feeding Thailand Non breast feeding DRUG AZT ANTEPARTUM 100 mg p.o 3hrly No 43 .H. p. IX. 45) Ergotamine** Ergotamine** (Various forms) (Various forms) • Some of the contra−indicated drugs listed are based on theoretical considerations.H. drugs with low therapeutic indices yet with suspected major metabolic contribution from cytochrome P450 3A. HIV−related drugs with overlapping toxicities BONE MARROW SUPPRESSION Cidofovir Cotrimoxazole Cytotoxic Chemotherapy Dapsone Flucytosine Ganciclovir Hydroxyurea Interferon−primaquine Pentamidine Ritonavir Stavudine Pyrimethamine Ribavirin Rifabutin Sulfadiazine PERIPHERAL NEUROPATH Didanosine Isoniazid Stavudine Zalcitabine Didanosine Lamivudine (children) PANCREATITIS NEPHROXICITY Cotrimoxazole Adefovir HEPATOTOXICITY RASH Delavirdine Abacavir Aminoglyco−Sides Efavirenz Amphotericin B Cidofovir Foscarnet Indinavir Pentamidine Fluconazote Isoniazid Itroconazole Ketoconazole Nevirapine NRTIs Protease inhibitors Rifabutin Rifampin Dapsone Amprenavir Contrimo−Xazo X.H.o. CYP2D6.o starting at 36 weeks gestation INTRAPARTUM 1v 2mg/kg loading.H.H.E. Actual interactions may or may not occur in patients.o. 45) (D.E.E. or unknown pathways are included in this table. 45) (D.(Vasoconstrictor) (D.o. bd. 45) (D.H. 45) Ergotamine** Ergotamine** (Various forms) (Various forms) (D.

starting at 36 weeks gestation 300mg AZT+ 150mg 3TC p. Ltd.o bd for 1 week 37% (infection status at 6 weeks age) VIVNET Breast feeding No 200mg single dose at the onset of labor No 47% (infection status at 6 weeks) Design.o 3 hourly 300mg AZT + 150mg 3TC p.o. p. layout. Kenya tel: 254 2 729502.Cote D voire AZT Breast feeding Cote D voire AZT Burkina Faso breast feeding Africa−Petra AZT +3TC Arm A 67% Breast feeding 300 mg p.o bd for 1 week AZT 4mg/kg + 3TC 2mg/ kg p.o. starting at 36 weeks gestation 300mg p. Box 418 Sarit centre: Tel: 443248/446570 BACK COVER Preparation and printing of this document was made possible by funding and assistance from the World Health Organization and United Nations Programme on HIV/AIDS (UNAIDS) Republic of Kenya World Health Organization National AIDS and STD Control Programme (NASCOP) PO Box 19361. Nairobi. starting at 36 weeks gestation 300 mg p.o at the 300mg bd for 1 onset of labour week No 300mg AZT + 150mg +3TC .o. Bd. bd.o bd for 1 week AZT 4mg/kg + 3TC 2mg/ kg p.o bd for 1 week 2mg/kg single dose in the first 72 hours Africa−Petra Arm B 67% Breast feeding AZT 300mg +3TC 150mg (combivir) No 300mg AZT+ 150mg 3TC p.ke 44 .714972 email: headnascop@iconnect. colour separations and printing done by TESSA Productions Co.o 3hrly No No 47% (infection status at 6 weeks age) 38% (infection status at 6 months age) 38% (infection status at 6 months age) 600mg p.o 3 hourly 300mg AZT + 150mg 3TC p.co.