Seminar on hiv diagnosis and management by Dr Sohanlal Sharma

HIV - Diagnosis and Management

Guide: Dr.S.L. Mathur sirPresented by Dr.Sohanlal Sharma

Introduction• HIV, the etiological agent of AIDS, belongs to lentivirus subgroup of

the retroviridae family

• The first indication of this new syndrome came in 1981 in homosexual drug addict males in USA

• they had two things in common- Pneumocystis pneumonia and Kaposi’s sarcoma.

. Recently its origin has been traced to Kinishasa in CONGO.

• AIDS Pandemic is primarily caused by HIV-1M.

Routes of transmission

Diagnosis of AIDSWHO case definition for AIDS surveillance

Major signs:• Wt loss more than 10%

• Chronic diarrhea for more than one month.

• Fever more than one month.

Minor Signs:• .Persistent cough more than a month

• .Gen. pruritic dermatitis

• .History of herpes Zoster

• .Oropharyngeal Candidiasis

• . Gen lymphadenopathy

Laboratory Diagnosis of HIV infection

1) Non Specific Tests-

a) Total Leukocyte and lymphocyte

b) T cell subset.

c) Platelet count-

d) Lymph node biopsy


2.Specific Tests for HIV infection- These include demonstration of -

• HIV antigen,

• Antibodies,

• Viral nucleic acids or other components and

• Isolation of virus

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i) Detection of antigen

o Following a contact, as by blood transfusion, the viral antigen may be detectable in blood after about 2 weeks.

o If the infecting dose is small, as following a needle stick injury, the process may be considerably delayed.

o The major core antigen p24 is the earliest virus marker to appear in blood.



• i) Detection of antigen (contd.)• Free p24 antigen disappears from circulation and

remains absent during the long asymptomatic phase to reappear only when severe clinical disease sets in.

• The p24 Capture ELISA assay, which uses anti p24 antibody as the solid phase can be used for this.

• This test is positive in about 30% of the infected persons.

• In the first few weeks after infection and in the terminal phase, the test is uniformly positive.



• Detection of antibodieso It takes 2-8 weeks to months for the antibodies to appear in

circulation

o IgM antibodies appear first, to be followed by IgG antibodies

o Once antibodies appear they increase in titer for the next several months

o IgM antibodies disappear in 8-10weeks while IgG antibodies remain through out.



• Detection of antibodies (contd.)• Screening tests and supplemental tests.

Screening tests include-

o ELISA- ELISA

o p24 Capture ELISA assay



ELISA

1) First generation - whole viral lysates

2) Second generation - recombinant antigen

3) Third generation - synthetic peptide

4) Fourth generation - antigen + antibody (Simultaneous detection of HIV antigen and antibody) - HIV duo



ii) Supplemental Tests

a)Western Blot Test

b) Indirect Immunoflorescence test

c)Radio ImmunoPrecipitaion Assay

iii) Rapid Tests

a) Dot Blot assay

b) Particle Agglutination tests

c) HIV spot and comb test

d)Fluorimetric micro particle technologies



• Three different techniques namely RT-PCR, nucleic acid sequence based amplification (NASBA) and branched-DNA (b-DNA) assay have been employed to develop commercial kits.

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Who to test When to test

Pregnant women andmale partners

At first antenatal care visitRe-test in third trimester or peripartumOffer partner testing

Infants and children <18 months old

At 4–6 weeks for all whose mothers are HIV Positive or status uncertain; Final status after 18 months and/or when breastfeeding ends

ChildrenEstablish HIV status for all health contacts Tell their HIV status & parents or caregiver’s status

AdolescentsIntegrate into all health care encounters.Annually if sexually active; with new sexual partners

Tests of Choice for Infants & Children < 18 Months of Age

Tests used for the diagnosis of HIV in children

Test Recommended / Not Reason

HIV ELISA NoFalse +ve due to persistent maternal antibodies

HIV p 24 Antigen Yes, butLower sensitivity than PCR (27% at 6 weeks)

HIV viral culture Yes, butCostly, result takes 2-4 wks, not readily available

HIV DNA PCR Yes 98% sensitive from 4 weeks of ageTesting Related to HIV

Clinical Manifestations

• AIDS is only the last stage in the wide spectrum of clinical features in HIV infection.

• The center for disease control (USA) has classified the clinical course of HIV infection under various groups.

• Acute HIV infection• Asymptomatic or Latent infection• Persistent generalized lymphadenopathy (PGL)• AIDS related complex• Full blown AIDS (Last stage)


NRTI NNRTI Protease Inhibitor OTHERS

Zidovudine (AZT) * Nevirapine (NVP)* Lopinavir (LPV)* Integrase Inhibitors

Stavudine (d4T)* Efavirenz (EFV)* Ritonavir (RTV)* Raltegravir

Lamivudine (3TC)* Atazanavir (ATV) Fusion Inhibitor

Emtricitabine (FTC) Saquinavir (SQV) Enfuviritide (T-20)

Didanosine (ddI ) Indinavir (IDV) Chemokine Co Receptor(CCR5 / CXCR4)

Antagonists)Abacavir (ABC) Nelfinavir (NFV)

NtRTI: Amprenavir (APV)

Tenofovir (TDF)*Fosamprenavir, (FPV), Tipranavir (TPV), Darunavir (DRV)

Maraviroc (CCR5 co receptor antagonists)

* The highlighted drugs are NOW available in the NACO ART programme

ManagementClasses of ARV Drugs

RT

Provirus

ProteinsRNA

DNA

RNA

DNA

DNA

RT

RNA

RNA

DNA

DNA

DNA

Viral regulatoryproteins

Viral protease

Reversetranscriptase

Viral integraseIntegrase Inhibitor

Mechanism of Drug Action

ProteaseInhibitorsLopinavirRitonavir

Reversetranscriptase

Zidovudine

Stavudine

Lamivudine

Nevirapine

Efavirenz

FusionInhibitor

ARV Clinical Pharmacology

Indication of ART

First-line ARTPreferred

first-line regimensAlternative

first-line Regimens

Adults(including pregnant andbreastfeeding women and adults with TB and HBV coinfection) TDF + 3TC (or FTC) + EFV

AZT + 3TC + EFVAZT + 3TC + NVPTDF + 3TC (or FTC) + NVP

Adolescents (10 to 19 years) ≥35 kg

AZT + 3TC + EFVAZT + 3TC + NVPTDF + 3TC (or FTC) + NVPABC + 3TC + EFV (or NVP)

Children 3 - 10 years and adolescents <35 kg

ABC + 3TC + EFV

ABC + 3TC + NVPAZT + 3TC + EFVAZT + 3TC + NVPTDF + 3TC (or FTC) + EFVTDF + 3TC (or FTC) + NVP

Children <3 yearsABC orAZT + 3TC + LPV/r

ABC + 3TC + NVPAZT + 3TC + NVP

NEW

Association between OIs & CD4 Count

Approach to OIs

Prevention of OIs

Timing of ART with TB

• ART should be started in all TB patients, including drug-resistant TB,irrespective of the CD4 count

• AKT should be initiated first, followed by ART as soon as possiblewithin the first 8 weeks of treatment.

• HIV-positive TB patients with profound immunosuppression (CD4<50) should receive ART immediately within the first 2 weeks of AKT .

• ART should be started in any child with active TB disease as soon aspossible and within 8 weeks After the initiation of AKT irrespective ofthe CD4 and clinical stage.

• Preferred NNRTI is EFV in patients starting ART while on AKT .

Timing of ART with Cryptococcal meningitis

• Immediate ART not recommended in cryptococcal meningitis due to the high risk of IRIS with CNS disease, which may be life-threatening .

• Among PLHIV with a recent cryptococcal meningitis,

– ART initiation should be deferred until there is evidence of a sustained clinical response to antifungal therapy and

– after two to four weeks of induction and consolidation treatment with amphotericin containing regimens combined with flucytosine or fluconazole; or

Healthcare

Seminar on hiv diagnosis and management by Dr Sohanlal Sharma