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Integrated session

HIV

Presenters
Ashwini E Haritha Moderators
Adithya Vikraman Navneeta Desikan Dr. Glennys
Jothilakshmi Anirudh K Dr. Shravana kumar
Sushmitha Gowtham S Dr.Manju Aishwarya
Sneha T Dr. S.Anandhalakshmi
CASE HISTORY :

 A 27 year old woman , presents to the antenatal clinic at 16 weeks of


pregnancy . This is her second pregnancy – her first child was delivered
by caesarean section , is now 8 years old .

 What are the recommended investigations at present ?


Recommended investigations for antenatal mother :

 Routine investigations :
This include Complete Blood Count : Hemoglobin levels , Urine analysis, Blood
glucose etc…
 VDRL/ RPR Tests (for what ?)
 USG
 Blood grouping
 Is HIV screening recommended for her ?
 If yes what is the protocol to be followed according to
National AIDS control organisation (NACO) guidelines?
Before getting her tested!!!!!

 Consent : In written format should be taken before the test


is done. Patient should be explained about the nature of test
being performed.
 Confidentiality is to be maintained.
 Counselling : must be provided to motivate individuals to
tell spouse or family and induce behavioural changes. Both
Pre-test and Post test counselling is required .
Strategies of HIV testing- India

 What are the test that can be done ?


 ELISA/Simple/Rapid test – E/S/R
 Supplemental test – western blot & line immunoassay
(indeterminate result)
Naco guidelines:

 Strategy I
 Strategy IIA
 Strategy IIB
 Strategy III
STRATEGY I :

 It is done for transfusion and transplantation safety ; for the


screening for the blood donors in blood banks .
 Only one test should be done. If found reactive , then the unit
of blood is destroyed .
STRATEGY / ALGORITHM 1
(For transfusion / transplantation safety) - one test kit required

A1

+ve -ve
Consider positive Consider negative

Destroy the unit of blood as per guidelines.


Refer to Integrated Counselling and Testing Centre for confirmation of status
after consent .
STRATEGY IIA

 It is done for sentinel surveillance of HIV infection to estimate the


prevalence of infection .
 UAT : The method here is called unlinked anonymous testing , which
involves screening of blood specimens taken for purpose other than HIV
TESTING .
 The samples are decoded of personal identifiers .
 This process occurs without informed consent .
Strategy / algorithm IIA
(For surveillance) 2 test kits required
A1

A 1 +ve A 1 -ve
Report negative
A2

A 1 + ve A 2+ve A 1 +ve A2 -ve


Report positive Report negative
STRATEGY IIB

 It is followed for the diagnosis of HIV / AIDS in symptomatic


patients .
 Positive result of first test should be confirmed by second test .
 If the second result is negative then a third test is done for
confirmation .
Strategy / Algorithm IIB-
(For diagnosis of an individual with AIDS indicator disease symptoms)
2 or 3 test kits required
A1

A 1 +ve A 1 -ve
A2 Report negative

A 1 +ve A2-ve
A 1 +ve A2+ve
Report positive with A3
post test counseling
A 1 +ve A2- ve A3+ve A 1+ve A2- ve A3-ve
Indeterminate Report negative
STRATEGY III

 It is done for the diagnosis of asymptomatic HIV patients , antenatal


screening and screening of patients awaiting surgeries .
 All positive results in first test should be confirmed by second and third
test.
 Positive report is sent only if all three test results are found reactive .
Strategy / algorithm III
(For detecting HIV in asymtomatic individuals)
3 test kits required
A1

A1 +
A 1 -ve
A2 Report negative
A 1 +ve A2 -ve
A 1 + A2+
A3
Report positive
A3
A 1 + A2 -ve A3+ A 1+ A2- ve A3-ve
Indeterminate
A 1 + A2 + A3+ve A 1 + A2 + A3-ve High risk consider
Report positive with Indeterminate indeterminate
post test counseling
Low risk consider negative
 For indeterminate results of strategy IIB and III ( first test is
positive but second or third test is negative ) Repeat the test
after 2 – 3 weeks and the sample should be sent to reference
centre for confirmation by WESTERN BLOT or RT – PCR .
Case history

 The investigations revealed that she was retroviral positive.


Hence she was referred to an integrated counselling and testing
centre (ICTC).
 On further evaluation, CD4 count was 324 cells/µl.
 How do we explain the genesis of immunodeficiency
Why CD4 count decreases?
Morphology of the virus

 Envelope:
Lipid part : Host derived
Protein part : gp120 and gp41
 Nucleocapsid:
Icosahedral capsule
Cylindrical Inner core
- ssRNA
- viral enzymes
STRUCTURE OF VIRUS
HIV genes and antigens

 Structural genes
Antigenic variation:
Duegag : codes
to error for nature
prone core of and shelltranscriptase
reverse of virus enzymes,
mutations
pol :are seenfor
codes in env
viralgenes leading to formation of different
enzymes
serotypes, subtypes, and Circulating recombinant forms CRFs
env : codes for envelope glycoprotein
 Non-structural genes
codes for viral replication and pathogenesis.
HIV Serotypes

 Serotype I (HIV-1): divided into group M,N, and O.


* Each group divided to ten subtypes A- J
sub-subtypes like A1and A2 or F1 and F2.
* Circulating recombinant forms (CRFs):
SEROTYPES----->GROUP----->SUBTYPES----->SUB-SUBTYPES
Recombinant forms between two subtypes : subtypes A and E CRF_01 AE
 Serotype II (HIV-2):
 Comprises of eight groups (A-H)
Modes of entry of HIV:

 Type of exposure risk %


 Sexual 0.1-1%
 Blood transfusion >90%
 Tissue or organ donation 50 -90%
 Injection and injuries 0.5 – 1%
 Mother to baby 15- 30%
MECHANISM OF ENTRY OF VIRUS:

 1.Attachment of gp120 to
a. CD4 receptor on T-Helper cells
b. CXCR4 receptor on T-lymphocytes
c. CCR5 receptor on macrophages
d. DC-SIGN receptor on dendritic cell
 2.Fusion of HIV to host cell with help of gp41.
 3.Penetration and uncoating of nucleocapsid and release of two
copies of ssRNA and viral enzymes.
 4.Reverse Transcription:
ssRNA -----> ssDNA -----> dsDNA
 5.Pre-integration complex:
A complex consisting of linear dsDNA, gag matrix protein,
accessory vpr protein and viral integrase migrates to the host cell nucleus.
 6.Integration:
The viral dsDNA gets integrated into the host cell
chromosome, mediated by viral integrase, called provirus.
 7.Transcription : Viral RNA is synthesized by host cell.
 8.Viral Protein synthesis.
 9.Protease enzymes cleaves peptides to various functional HIV
enzymes.
 10.Virion budding and virion maturation.
Pathogenesis
Virus destroys the cell as a result of
budding

But few cells are infected:


Early stage of infection 1:10,000
Late 1:40
HIV could kill sub population of
precursor cells
People develop AIDS even when they
have HIV that does not lyse cells
Why do all T4
cells
1. PUNCTURED
disappear?
MEMBRANE
WHY DO ALL T4 CELLS DISAPPEAR? - 2
But syncytia not
common
Infected CD4 Most T4 cells are
cell Cells Fuse not HIV+
Gp120 positive Could “sweep up”
uninfected cells

Syncytia may be
Uninfected poor or ineffective
Killing of CD4 cells CD4 cell at immune
2. Syncytium Gp120 response
Formation negative
Why do all T4
cells
disappear?

Cytotoxi
c T cell

Killing of CD4 cells


3. Cytotoxic T cell-mediated
lysis
BUT: Most cells
are not infected
Killing of CD4+ cells
4. Binding of free Gp120
to CD4 antigen makes
uninfected T4 cell look
like an infected cell
Complement-mediated
lysis
Could account for the
loss of uninfected T4
cells
Natural course of HIV infection
 Acute HIV disease/Acute retroviral syndrome
* HIV destroys the infected T cells and spills over to the blood stream to cause
primary viremia.
* There is significant drop in T-helper cell count.

 Asymptomatic stage:
* Both humoral and cell mediated response are activated.
* Viremia drops and T-Helper cell count becomes normal.
* This is a stage of clinical latency not microbiological latency.
Natural course of HIV infection

 Persistent Generalized Lymphodenopathy (PGL):


As a result of HIV replication in lymph nodes, 25-30% of infected
people who are asymptomatic, develop lymphadenopathy.
 Symptomatic HIV infection (AIDS Related Complex, ARC) :
After variable period of clinical latency, CD4 T cell level
starts falling and develops constitutional symptoms.
 AIDS:
The patient moves towards an advanced stage of disease characterised by less than
200 T-Helper cells /µl of blood, high viral load and other opportunistic infections.
Window period
Types of progression in HIV

 Rapid progressors: percentage of HIV-infected individuals rapidly progress to AIDS


if they fail to take the medication within four years after primary HIV-infection
and are termed Rapid Progressors (RP).
 Long Term Non-Progressors: subset of individuals who are persistently infected
with HIV-1, but show no signs of disease progression for over 10-30 years and
remain asymptomatic. RNA : < 5000 copies/ml
 Elite controller: After long time 10-30years without ART they show < 50 RNA
copies/ml
 Highly exposed persistently seronegative: Exposed but remain seronegative.
 What are the clinical manifestations associated with
retroviral infection?
HIV Staging & Classification
 Given by WHO World Health Organisation
 Separate staging for
1. Adults & Adolescents
2. Children < 15 years

 Four hierarchical clinical stages.


 Stage 1 (asymptomatic) to stage 4 (AIDS).
 Assigned to a stage even if they have at least one disease
pertaining to that stage.
 Patients remain at a higher stage even after recovery.
Adults & adolescents

Stage 1

 Asymptomatic
 Persistent generalized lymphadenopathy
Adults & adolescents
Stage 2

 Moderate unexplained weight loss (>10%


of presumed or measured body weight)
 Recurrent respiratory tract infections
 Papular pruritic eruption
(sinusitis, tonsillitis, otitis media,
 Fungal nail infections
pharyngitis)
Seborrhoeic dermatitis
 Herpes zoster
 Angular cheilitis, Recurrent oral
ulceration
Adults & adolescents
Stage 3

 Unexplained severe weight loss (>10%


of presumed or measured body weight)
Severe bacterial infections (such as
pneumonia,
 Unexplained chronic diarrhoeaempyema,
for pyomyositis, bone
longer than 1 monthor joint infection, meningitis, bacteraemia)
  Acutefever
Unexplained persistent necrotizing ulcerative stomatitis,
gingivitis
(intermittent or constant for or periodontitis
longer than
1 month)  Unexplained anaemia (<8 mg/dl),
 Neutropaenia (0.5x109) and/or chronic
Persistent oral candidiasis
thrombocytopaenia (<50 x 109)
 Oral hairy leukoplakia
 Pulmonary tuberculosis
ADULTS & ADOLESCENTS
Stage 4
 HIV wasting syndrome(Slim disease):severe weight loss
(>10%), chronic diarrhoea (>1 month) & unexplained
persistent fever (1 month)

 Opportunistic infections
 Neoplasia
 Kaposi’s sarcoma
 Invasive cervical cancer
 Lymphoma(cerebral, B-cell and non-Hodgkin)
 Other conditions
HIV encephalopathy
Symptomatic HIV-associated nephropathy or
cardiomyopathy
Which are the most common opportunistic infections that are
associated with HIV?
OPPORTUNISTIC INFECTIONS

 Opportunistic infections (OIs) are infections that occur


more frequently and are more severe in individuals with
weakened immune systems, including people with HIV.
SYSTEMIC APPROACH TO THE INFECTION

 CNS
 Respiratory system
 GIT
GIT related infections

 Giardiasis
 Cryptosporidiosis
 Isosporiasis
Chronic diarrhoea
 Microsporidiosis
 CMV - colitis associated with fever, crampy abdominal pain,
and frequent (often bloody) stools.
Respiratory system

 Pulmonary tuberculosis - most common opportunistic infection


 Nontuberculous mycobacterial infection :
Namely???.
Mycobacterium avium complex (MAC), Mycobacterium kansasii,
and Mycobacterium abscessus.
 Pneumocystic jirovecii pneumonia (PCP)
 Recurrent pyogenic bacterial pneumonia.
Causes of bacterial pneumonia??
CNS

 Toxoplasmosis
 Cryptococcal meningitis
 CMV- encephalitis
retinal exudates and retinitis
WHAT IS CD4+ TEST & WHY IT IS DONE ?

 CD4+ count / test determines the number of CD4+ cells


 HIV attacks and destroys the CD4+ cells and decreases immunity
1. For staging of HIV patients
2. To determine the immune status
3. To determine prophylactic treatment requirement in such
patients
 Measurement of the CD4+ T cell count and plasma level of HIV RNA are
important parts of the routine evaluation and monitoring of HIV –
infected individuals
 The CD4 + T cell count = accepted indicator of immunocompetence of
HIV patients.
 There is a close relationship between CD4+ T cell count & clinical
manifestations of HIV patients.
< 200 / µl Pneumocystis jiroveci
< 50 / µl CMV disease and Mycobacterium avium intracellulare
<100/ µl Toxoplasmosis
<500 / µl is a clear indication to initiate antiretroviral therapy

 Patients should have their CD4+ counts measured at the time of


diagnosis & every 3-6 months thereafter
Correlation of occurrence various opportunistic infection with CD4 count
 What is the most common skin manifestations associated with
retroviral infection?
Mucocutaneous manifestations of HIV

Classification:
• Infectious manifestation
• Non-infectious manifestation
• Cutaneous adverse drug
• Specific mucosal manifestation
• Hair manifestation
• Nail manifestation
INFECTIOUS MANIFESTATION
VIRAL INFECTIONS BACTERIAL INFECTIONS
Herpes simplex virus Staphylococcus aureus
Epstein-Barr virus mycobacterial infection
Human Papilloma
Molluscum contagiosum

FUNGAL INFECTIONS PARASITIC INFECTIONS


Dermatophytosis Arthropod infection
candidiasis Protozoal infection
VIRAL INFECTIONS: PAINFUL ULCERS OF LONGER THAN 1 MONTH IS A AIDS DEFINING CONDITION

 HERPES SIMPLEX VIRUS:


HERPETIC WHITLOW
HUMAN PAPILLOMA VIRUS
EPSTEIN BARR VIRUS
MOLLUSCUM CONTAGIOSUM

UMBLICATED PEARLY WHITE PAPULES


BACTERIAL INFECTIONS:

 Bacillary angiomatosis
 Perianal ulcer
FUNGAL INFECTIONS:

Dermatophytosis

 Oral candidiasis
Non-infectious disease

 Papulosquamous disorders
 Pruritic eruptions of hiv
 Pigmentary disorders
 Cutaneous adverse drug reactions
 Neoplasms
Non-infectious infection

Kaposi sarcoma
Psoriasis
SEVERE DRUG REACTIONS:

Stevens-johnson syndrome
OTHER MANIFESTATION:
Case history

 She had received a negative result for tuberculosis. And was started on
antiretroviral therapy.
 What is the recommended chemoprophylaxis for CD4 count <350
cells/µl?
Chemoprophylaxis for PCP
 Cotrimoxazole Preventive Therapy [CPT]:
1. CD4 count < 350 cells / cu.mm
2. WHO clinical stage 3 & 4.
 Alternate regimen - Dapsone 100mg O.D
 Timing the Initiation of cotrimoxazole in relation to initiating ART
1. Start cotrimoxazole prophylaxis first
2. Start ART after starting cotrimoxazole / as soon as CPT is tolerated & patient
has completed “preparedness phase” of counselling
Isoniazid preventive therapy [IPT]

 About 50% of adults have latent TB infection [LTBI]

 Isoniazid
1. Most effective bactericidal anti- TB drug
2. Protects against progression to active disease
3. Prevents TB re-infection after exposure to open case of TB
 She is receiving daily co-trimoxazole prophylaxis for preventing
opportunistic infections and was started prior to ART.
 At the 36 weeks of gestation she is admitted for safe
confinement.
MANAGEMENT

 Here, as the woman has been tested as HIV positive she


should be advised to:
 Continue antiretroviral therapy(Tenofovir 300mg, Lamivudine 300mg
and Efavirenz 600mg)
 Should continue lifelong ART
 Take iron and folate supplementation
Safe Delivery Techniques
 Mother to child transmission risk is increased by prolong rupture of membranes,
repeated PV examination, assisted instrumental delivery, invasive foetal monitoring
procedures, episiotomy, and prematurity. Thus while delivering HIV infected women
observe:
 Universal work precautions
 Do not rupture membranes artificially
 Minimise vaginal examination and use aseptic techniques
 Avoid invasive procedures and instrumental delivery as much as possible
 Avoid routine episiotomy as far as possible
 Suctioning newborn with nasogastric tube should be avoided unless there is meconium
staining of liquor.
HIV EXPOSED INFANT

 Infants born to mothers infected with HIV until it can be


reliably excluded and the infants are not exposed to HIV
through breast feeding.
POST NATAL CARE OF MOTHER AND INFANT
Post natal Care of Mother Care of HIV exposed Infant
 Routine postnatal care hygiene and  Exclusive breast feeding for 6 months
nutrition  Syrup Nevirapine NVP (10 mg in 1mL
 Breast feeding counselling suspension) from birth till 6 weeks
prophylaxis from birth to 6 weeks
 Continue ART lifelong
 Cotrimoxazole prophylaxis from 6
weeks to 18 months
 Regular immunization
 Follow up of child
RECOMMENDATIONS FOR INFANT FEEDING

 Exclusive breast feeding for at least 6 months.


 Exclusive replacement feeding may be considered only in
situations where breast feeding can not be done.
ESTIMATED RISK OF VERTICAL TRANSMISSION
What would be the plan of management? Justify

 The patient was taken up for caesarean section as there is


history of previous LSCS.
STANDARD PRECAUTIONS

 They are meant to reduce the risk of transmission of


blood borne & other pathogens from both recognized
and un-recognized sources.

 Basic level of infection control precautions, which are


to be used, as a minimum in the care of all patients.
PRECAUTIONS

Hand hygiene
PERSONAL PROTECTIVE EQUIPMENT
OTHER PRECAUTIONS

 Respiratory hygiene & cough etiquette

 Safe handling & safe disposal of sharps

 Safe decontamination & of contaminated wastes


How will you screen for the HIV transmission to the newborn?
Infant screening for HIV – Early infant diagnosis
Dried Blood Spot (DBS) card test – detection of Proviral DNA
Eligibility: Infants and children born to HIV +ve mothers.

Infants and children with signs and symptoms of HIV.

If baby is <6 weeks HIV 1 DNA PCR is not recommended.


Infants >6 weeks but <6 months old and born to HIV positive Mother
SCREENING OF INFANT
Collect and Send Dried Blood Spot (DBS) of babies between
6 weeks to <6 months of age for HIV -1 DNA PCR (AT ICTC)

HIV-1 DNA detected Infant is HIV-1


HIV-1 DNA not detected
uninfected
HIV -1 DNA not detected
Collect and send Whole Blood by Whole Blood
Specimen for HIV-1 DNA PCR
(At ART Centre)
Guidance 1 – Lab will request
HIV-1 DNA detected for Fresh Whole Blood sample
from ART Centre if result is
discordant and rely on the final
Infant is HIV-1 infected
whole blood test result
Child of age 6-18 months born to HIV positive mother
Collect blood and test for HIV antibodies using rapid test.

Rapid test positive Rapid test negative – does


not need HIV -1 DNA PCR

Send Dried Blood Spot (DBS)of child for HIV-1 DNA PCR

HIV-1 DNA detected HIV-1 DNA not detected

Collect and send Whole Blood Specimen for HIV-1 HIV-1 DNA not
DNA PCR (At ART Centre) detected

Guidance 1 – Lab will request for Fresh


HIV-1 DNA detected Whole Blood sample from ART Centre if HIV-1 DNA not detecte
result is discordant and rely on the final
whole blood test
Infant is HIV-1
PREVENTION

 All pregnant and breast feeding women with HIV receive lifelong ART regimen
 Postpartum ART initiation to mother and prophylaxis to child
 HIV exposed infants should be followed-up and managed
 All babies detected positive <2years of age are given pediatric ART
 HIV-exposed children should be immunized
Thank you