HIV and AIDS
Presenter: MAHMOOD AHMED
Learning Objectives: • Origin of HIV • Lifecycle of HIV-1. • CD4 cell and host defense system. • Natural history of HIV-1 disease. • Immune responses to HIV-1 and mechanisms of immune evasion by HIV. • Drugs • Nursing care Origins of HIV
• • • • • • HIV similar to virus found in monkeys and apes called SIV (simian immunodeficiency virus). To identify ancestry of HIV scientists have sequenced various HIV strains and compared them to various SIV strains. HIV-1 is most similar to an SIV found in chimps and HIV-2 is most similar to an SIV found in a monkey called the sooty mangabey. HIV-1 occurs in three different subgroups (called M,N and O) and each appears closely related to a different chimpanzee SIV strain. Thus, it appears that HIV-1 jumped to humans from chimps on at least 3 occasions. Most likely the virus was acquired through killing and butchering chimps and monkeys in the “bushmeat” trade.
When did HIV move to humans?
Sequence data from several group M strains has been used estimate when HIV moved from chimps to humans. Korber et al. (2000) analyzed nucleotide sequence data for 159 samples of HIV-1 strain M. Constructed a phylogenetic tree showing relatedness to a common ancestor of the 159 samples. Extrapolating based on rates of change of different strains suggests that subgroup M probably infected humans in the early 1930’s.
Human Immunodeficiency Virus
Human Immunodeficiency Virus
. HIV is a retrovirus. A retrovirus is an RNA virus which uses DNA as an intermediary for its replication. A virus is unable to replicate (reproduce) on its own and must first infect a living cell in order to replicate.Origins of HIV
Likely resulted from hybridization (merging) of two simian (monkey) viruses HIV moved to humans in Africa around 1930 or earlier
HIV and SIV Viruses
HIV and SIV
A virus is the simplest. most primitive life form on earth.
mucosaCells White blood cells Macrophages -Complement
Adaptive Immunity T-Lymphocyte
High Specificity/ Memory Cells
.HIV Life Cycle
HIV Variability HIV has enormous potential for change (mutations) The HIV copies in an infected person are not all identical but are rather like a swarm of closely related viruses. ARV drug resistance. Escape from immune control. Effects of HIV Mutations Mostly of no consequence Viral fitness increased or decreased Viral infectivity/pathogenicity increased or decreased. Immunology Host Defense System Self versus Non-Self (antigen)
-Skin. Reverse Transcriptase is a very error-prone enzyme.
How HIV causes AIDS HIV invades immune system cells especially helper T cells.Helper Function of CD4 Cells
T helper cell (CD4)
Cytotoxic T Lymphocyte (CD8)
Antibody secreting (plasma) cell
White Blood Cell Distribution
Neutrophils Lymphocytes Basophils Eosinophils Monocytes Absolute/Total cells/uL 4000 1000 500 Percent 55% WBC 30% Lymphocytes
Surrogate Markers of HIV Disease CD4 is an indicator of the strength of the immune system. it begins to divide into memory T cells and effector T cells. Memory T cells Memory T cells do not engage in current fight against the virus. Effector T cells Effector T cells attack the virus. These helper T cells have a vital role in the immune system. Viral Load is an indicator of the amount of viral replication. They produce signaling molecules called chemokines that stimulate B cells to produce antibodies to the virus. Effector T cells also stimulate macrophages to ingest cells infected with the virus. When a helper T cell is activated (by having an antigen [a piece of foreign protein] presented to it.
. Instead they are long-lived and can generate an immune response quickly if the same foreign protein is encountered again.
Viral reservoirs in resting infected cells.
Viral disguise Killer T cells deplete helper T cells (those that produce memory cells that can remember and recognize HIV). after a finite number of rounds of replication the body’s supply of helper T cells becomes exhausted. but the immune system now primed to recognize and attack the viral protein. At CD4 counts between 200 and 500 cells/uL other conditions and opportunistic infections may begin to appear (Kaposi’s sarcoma. Mutant virus particles bearing new surface proteins survive immune system attack and begin new round of infection Each round of infection reduces numbers of helper T cells because they are infected by virus and destroyed. oral/genital candidiasis. immune activation resulting in immune dysfunction. herpes zoster. Development of humoral immunity (HIV-specific antibodies).
. generalized. etc. Non-specific.
In addition effector T cells stimulate killer T cells to destroy infected cells displaying viral proteins. but they may be more frequent. Dissemination of infection to lymph nodes. Loss of helper T cells is costly. tuberculosis. Clinical Latency At CD4 cell counts over 500 cells/uL many complications overlap with conditions found in uninfected populations (bacterial pneumonia. o Fever o Fatigue o Pharyngitis o Lymphadenopathy o Rash Pathogenesis of Acute HIV-1 Infection Initial infection of CD4 cells and macrophages at site of exposure. Burst of viral replication results in intense viremia. The immune system eventually is overwhelmed and collapses. Furthermore. Development of cellular immunity (HIV-specific CD4 and CD8 cells).). Continuous destruction and compensatory increased production of CD4 Lymphocytes. These new surface proteins are not recognized by the immune system’s memory cells. Viral load plateaus at viral set point. What’s the problem? Virus mutates and the proteins on its outer surface (gp120 and gp41) change. Natural History of HIV Infection Acute Retroviral Syndrome Non-specific ‘flu-like’ symptoms. Pathogenesis of Chronic HIV-1 Infection High turnover of CD4 cells. because each lineage of T cells has a limited capacity for replication. minor skin conditions).
g. MTCT. if total lymphocytes are 4000 cells per uL and 1000 of these cells are CD4 cells. 15-20% of children develop AIDS or die within 1 year. Immune Response in Children (2) Because the infant’s immune system is immature. the CD4% is 25%. CD4% is the percent of total lymphocytes that are CD4 cells. helper) cells drop below the level of 200 cells per mm blood (a healthy person has about 800) and your body cannot fight off simple infections
Immune Response in Children Viral set point is higher in children.. CD4. e. Disease progression similar to adults. disease progression is expressed as CD4%. HIV Transmission and Prevention Modes of Transmission Mucosa (genital/rectal) Blood (transfusion. 10% survive for a prolonged period (5-6 years).AIDS A low immune system can allow opportunistic infections to invade your body AIDS is a stage of disease where your immune (T. needle stick injury) Breast Feeding
Prevention Avoidance of infected mucosal secretions Safe blood transfusion service Post-exposure prophylaxis Prevention of Mother-to-Child Transmission Avoidance of breast feeding Universal precautions Hand washing Safe disposal of infected material TRANSMISSION OF HIV HIV is not transmitted by Public bath Coughing .food Sharing cups.plates or other Kissing utensils STAGES OF HIV TO AIDS Stage 1 – Primary Short.glasses.hugging Using telephones Water .occurs one to six weeks after infection no symptoms at all Infected person can infect other people Stage 2 – Asymptomatic
Lasts for an average of ten years This stage is free from symptom There may be swollen glands The level of HIV in the blood drops to very low levels HIV antibodies are detectable in the blood
Stage 3 – Symptomatic The symptoms are mild The immune system deteriorates emergence of opportunistic infections and cancers Stage 4 .sneezing Handshakes Insect bite Work or school contact Touching . flu-like illness .HIV AIDS • The immune system weakens • The illnesses become more severe leading to an AIDS diagnosis
Opportunistic Infections associated with AIDS • Bacterial • Tuberculosis (TB) • Strep pneumonia • Viral • Kaposi Sarcoma • Herpes • Influenza (flu)
they are Binding. Budding. Integration.Opportunistic Infections associated with AIDS • Parasitic o Pneumocystis carinii • Fungal o Candida o Cryptococcus HIV/AIDS Transmission
Mother to child
Multiple infections Transmission
Life Cycle of HIV There are 7 steps in the life cycle of HIV. Reverse transcription. Translation. Transcription.
resistance profiles and patient preference. or HAART. Reverse-transcriptase inhibitor(RTI) Protease inhibitors (PIs) Integrase inhibitors Entry inhibitors (or fusion inhibitors) Maturation inhibitors REVERSE-TRANSCRIPTASE INHIBITOR RTIs come in three forms: Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs) Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) Mechanism When HIV infects a cell. treatment history. The viral DNA is then integrated into the host chromosomal DNA. thus preventing HIV from multiplying Zidovudine(Azidothymidine. reverse transcriptase copies the viral single stranded RNA genome into a double-stranded viral DNA. typically three or four. the approach is known as Highly Active Antiretroviral Therapy. RTIs block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA. HIV viral load. APPROACHES FOR TREATMENT OF AIDS NATURAL ANTI HIV AGENTS CHEMOKINE (CCR5 and CXCR4) RECEPTOR ANTAGONIST ANTI-SENSE OLIGONUCLEOTIDES ANTI-CD4 MONOCLONAL ANTIBODY TNX -355 NANOTECHNOLOGY FOR HIV/AIDS TREATMENT MEDICINAL CHEMISTRY FOR THE TREATMENT OF AIDS Classes of drugs Antiretroviral (ARV) drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits. are taken in combination.Treatment When several such drugs. which then allows host cellular processes. The decision on when to start treatment should take into account.AZT)
. such as transcription and translation to reproduce the virus.
CD4. the virions released consist mainly of non-infectious particles. HIV is then unable to bind and enter human macrophages. another chemokine co-receptor found on CD4+ cells "parang gago" gp41. a protein on HIV surface that binds to the CD4 receptor CCR5. Tenofovir Tenofovir disoproxil fumarate (TDF or PMPA). maraviroc is a CCR5 receptor antagonist. AZT use was a major breakthrough in AIDS therapy in the 1990s. which block reverse transcriptase. Alpha Interferon
. closely associated with gp120. thereby blocking the conversion of the polyprotein into the mature capsid protein. a second receptor found on the surface of CD4+ cells. Two additional ones under investigation are bevirimat and Vivecon. that penetrates the cell membrane Maraviroc brand-named Selzentry. such agents slow the progression from HIV infection to AIDS Proteins involved in the HIV entry process. Saquinavir Integrase inhibitor INTEGRASE INHIBITORS are a class of antiretroviral drug designed to block the action of integrase. Because these viral particles have a defective core. an enzyme crucial to viral production in HIV-infected people. Raltegravir ENTRY INHIBITORS. also called CD4+ T cells gp120. marketed by Gilead Sciences under the trade name Viread. called a chemokine co-receptor CXCR4.
PROTEASE INHIBITORS (PIS) PIs prevent viral replication by inhibiting the activity of proteases Protease inhibitors were the second class of antiretroviral drugs developed. NNRTIs act allosterically by binding to a distinct site away from the active site known as the NNRTI pocket. a protein receptor found on the surface of helper T cells in the human immune system. Efavirenz brand names Sustiva and Stocrin NNRTI Unlike NRTIs. or Celsentri outside the U. Alpha interferon is a currently available agent in this class. AZT slows HIV spread significantly. which bind at the enzyme's active site.S. and binds to the chemokine receptor CCR5 and blocks the HIV gp120 (V3 loop) from associating with the receptor. CCR5-receptor antagonists Maturation inhibitor MATURATION INHIBITORS inhibit the last step in gag processing in which the viral capsid polyprotein is cleaved. a viral enzyme that inserts the viral genome into the DNA of the host cell. By blocking this step in HIV's replication cycle. but does not stop it entirely. sold under the names Retrovir and Retrovis. also known as fusion inhibitors This class of drugs interferes with the binding. fusion and entry of an HIV virion to a human cell. belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NRTIs). a HIV protein.AZT was the first approved treatment for HIV. Specifically. Maraviroc is an entry inhibitor.
000 Children with HIV/AIDS (2008) = and Adult HIV prevalence(%) (2008) = 0.100
ESCALATING EPIDEMIC OF HIV IN HIGH RISK GROUPS IN PAKISTAN POTENTIAL THREATS IN PAKISTAN
• • • • • • 100.
. Limited surveillance Voluntary counseling and testing systems Lack of knowledge among the general population and health practitioners.000 People living with HIV/AIDS (2008) = 96.000 homosexuals reported in Lahore in 2002 40% of 1.000 iv drug users in Pakistan (1 in 5 infected with HIV) 38.000 Women (aged 15+) with HIV/AIDS (2008) = 27. NON GOVERNMENTAL ORGANIZATIONS
54 NGOs are involved in HIV/AIDS public awareness and in the care and support of persons living with HIV/AIDS. only 300 cases of full-blown AIDS and another 2300 cases of HIV infection were reported to the National AIDS Control Program.• • • • • • • • • • • •
• • • • • • •
Interferons (IFNs) are proteins made and released by lymphocytes in response to the presence of pathogens—such as viruses.5 million annual blood donors not screened for HIV 20% of blood transfusions come from professional donors with high prevalence of infectious diseases Significantly large number of migrants and refugees. more needs to be done.
• • • •
UNDER-REPORTING Until September 2004.1% of the adult population in Pakistan Total Population (2008) = 180. The reasons for under reporting are: Social stigma attached to the infection. NATIONAL RESPONSE TO HIV/AIDS Pakistan’s Federal Ministry of Health initiated a National AIDS Prevention and Control Program (NACP) in 1987 In its early stages. but progressively began to shift toward a community focus The government has indicated in the recent scaling up of its response to HIV/AIDS. Prevention of HIV Transmission Strategies to prevent HIV transmission Personal strategies Public health strategies Safe practices: no risk of HIV transmission Risk reduction: reduces but does not eliminate risk Public health strategies to prevent HIV transmission Screen all blood and blood products Follow universal precautions Educate in safer sex practices Identify and treat STIs/other infections Provide referral for treatment of drug dependence Apply the comprehensive PPTCT approach to prevent vertical transmission of HIV ESTIMATED HIV BURDEN IN PAKISTAN
0. or parasites—or tumor cells.1% AIDS deaths (2008) = 5. bacteria.800.000 commercial sex workers with poor safe sex awareness in three major cities Estimated 60. the program was focused on diagnosis of cases that came to hospitals.
Safe. 2. Maintain isolation to protect client from other organisms. Maintain isolation precautions. We can protect drug users from becoming infected with HIV. protect from infection.
WHAT WE CAN DO??
UNAIDS Outcome Framework 2009–2011: nine priority areas We can reduce sexual transmission of HIV. Evidence of Kaposi’s sarcoma (purplish. Fever 8. Physiological integrity A. 3. and teach precautions to client. Provide education regarding disease process and greatly decreased risk of transmission to the newborn if treated with Zidovidine in the last trimester of pregnancy. Psychosocial integrity A.
NURSING CARE Assessment PHYSICAL ASSESSMENT
Assess for the following clinical manifestations: 1. intrapartal. We can enhance social protection for people affected by HIV. truck drivers. reddish brown lesions)
PSYCHOSOCIAL AND CULTURAL ASSESSMENT
1. Observe blood and body-secretion precautions. 2. 3. Health promotion and maintenance A. Provide opportunities for counseling. Anxiety about future of self and child. Diarrhea 6.1 million US dollars Enhanced program is making encouraging progress with expansion of coverage.
WORLD BANK RESPONSE
Largest financer of HIV/AIDS program in Pakistan Providing 37. We can prevent people living with HIV from dying of tuberculosis. postpartal) and for the newborn infant. Lymphadenopathy 5. 2. We can empower young people to protect themselves from HIV. and other highrisk groups. We can stop violence against women and girls. effective care environment A. Provide education for self-care regarding isolation precautions and prevention of infection. We can remove punitive laws. Planning 1. AIDS occurs most frequently in women with a history of IV drug use.
1. We can prevent mothers from dying and babies from becoming infected with HIV. We can ensure that people living with HIV receive treatment. Malaise 3. History of IV drug use and/or prostitution 2.
Ensure that the expectant woman:
. Evidence of opportunistic infection 7.Also working on education and prevention interventions targeting sex workers. Progressive weight loss 4. practices. But reaching less than 5 percent of the vulnerable population. 4. Follow blood and secretion precautions during all contact with expectant woman (antepartal. 4. policies. stigma and discrimination that Block effective responses to AIDS.
unaids.org/aids.htm http://www.gov/content files/Approved Meds to Treat HIV www. Participates in maintaining blood and body-secretion isolation.1.avert. 4.nih.com/content National Institute of Allergy and Infectious Diseases aidsinfo. Verbalizes knowledge of disease condition and implications for the future.worldaidscampaign.retrovirology.nacp. Is able to verbalize her feelings about her condition. 2.pk/wp-con
. Is protected from further infection.org www.who.
WORLD AIDS DAY WORLD AIDS DAY IS CELEBRATED ON 1st DECEMBER every year REFFERENCES
• • • • • • • • • www.gov.cdc.org www.org www. 3.gov/hiv www.