HIV Update For General Practioners 2013

Dr Madhu OswalSamvad HIV AIDS Helpline

Overview How to diagnose?

How to monitor after diagnosis ?

When to start ART?

What to start?

How to monitor after starting ART?

When to refer?

Samvad HIV Helpline 020-263812341/19/2013

Mayur Mr Mayur, 24 yr old,

called at 10 am on Sunday morning.

H/O Unprotected exposure (condom slipped) night before.

Wants to know if he is HIV infected- TODAY.

What to do?


6

“Window Period” Following HIV Infection

P24 a.gELISA

0 2 3 4(Weeks since infection)

a b

Viremia

AntibodyAsymptomatic

Acute HIV

syndromePrimary

HIV

infection

Source: S Conway and J.G Bartlett, 2003

Years

------------------------------------ PCR


Diagnosis in the window period

After 6 weeks-antibody tests

Elisa/Rapid

At approx 4 weeks- HIV Duo

At approx 2 weeks- HIV RNA

HIV DNA

P24 Ag test

A POSITIVE RESULT HAS TO BE CONFIRMED BY AN ANTIBODY TEST AFTER THE WINDOW PERIOD


HIV DNA or RNA HIV DNA or RNA tests are NOT recommended for

diagnosis in adults

False positive results in almost 20% of patients

Costs around Rs 4000.

The patients have to be subjected to antibody testing for confirmation after 6 weeks.


Take history: was the risk significant

Any symptoms or signs of STD-Treat

Test for baseline HIV status, Hbs Ag, ? Anti HCV

Explain about window period

Start PEP for HIV if indicated

Start Heb B vaccine course, if not vaccinated and HbS Ag neg.

Risk reduction counseling

If woman( Mayuri), Emergency contraception

What to do?


Post Exposure Prophylaxis


Drugs for Post exposure prophylaxis Basic regimen:

1. Tenofovir 300+ Emtricitabine 200mg OD OR

2. AZT 300 mg + Lamivudine 150 mg BD

Expanded regimen:

1. Above plus Atazanavir 300 + Ritonavir 100 mg OD

2. Lopinavir 400mg +Ritonavir 100 mg BD

All for 4 weeks

Test after 6 weeks and 3 months for HIV and Hep B


After 3 months…….. Mayur ‘s HIV test is Negative

Risk reduction counseling .


After 3 months…….. Mayur ‘s HIV test is Positive (……..May be because I

didn’t take his call on Sunday )

Now what?

1. Disclose Mayur that he is HIV positive?

2. Do Western Blot test

3. Do HIV DNA/ RNA test?

4. Repeat Elisa test?


Ist Rapid / Elisa.

Positive

II nd Rapid / Elisa

NegativeUninfected

Positive

Symtomatic

Infected.

Asymptomatic

III rd Rapid / Elisa

Negative

Equivocal W.B.

NegativeUninfected


Which test would you utilize when you suspect HIV

infection?

Elisa test

Rapid test

Western Blot test


ELISA for HIV antibody

Microplate ELISA for HIV antibody: coloured wells indicate reactivity


Elisa report

Positive


Rapid test

Uses ELISA principle

Takes 10 min to 30 mins to perform

Very simple to perform without any need to special apparatus

Can be used in G.P’ s clinic

Most have sensitivity and specificity comparable to ELISA


Rapid tests brands Determine

Triline

Retroquick HIV

Immunoblot

HIV Tridot

Comb AIDS 1/2,

HIV Comb

Retrocheck HIV


Step 1- Do Rapid Test in your clinic. If positive,

Step 2- Confirm with ELISA in a standard Lab.

WESTERN BLOT TEST

Positive for HIV 1


Western Blot Result Interpretation Results are interpreted as follows:

Negative: no bands

Positive: reactivity to gp120/160, plus either gp41 or p24

Indeterminate: one reactive band (or anything other than a positive test) should be repeated at a later time, e.g., 1-3 months later

Repeatedly indeterminate: no HIV infection


Western Blot test –

Not a “gold standard” test in India

Indeterminate results

High cost


Mayur has confirmed HIV test Now what?

Don’t know how to break the news, so keep silent

Refer to HIV specialist

Manage further


Mayur goes into depression Don’t turn up for 5 to 6

years.

Then one fine day…..he comes with Herpes Zoster


Initial evaluation: history Fever, night sweats, weight loss, cough (any duration): TB

Other OI’s: herpes zoster, chronic diarrhoea

ARV exposure with response

Co-morbidities: DM, HTN, CKD, Jaundice

Smoking, alcohol

High risk behaviour

Ask if he has any sexual partner, marital status , children


Initial evaluation: physical examination

Weight

Lymphadenopathy

Oral cavity

Hepato-splenomegaly, doughy feel of abdomen

Fundoscopic

Dermatological exam


Initial evaluation: Laboratory workup CBC with differential

Urinanalysis, creatinine

Blood sugar

Liver enzymes (optional)

Chest Xray/USG abdomen(before starting ART)

CD4 Count

Serologic

VDRL, TPHA

HbsAg, anti-HCV

sCRAG (in pts with CD4<200)

Cervical PAP smear in Mayuri


Tests NOT recommended Exceptional situations only

Plasma viral load

ARV resistance testing

Fasting lipids

CMV, Toxo serology

TB tests

TB ELISA

Tuberculin testing

IGRA assays( TB Gold, Quantiferon)


Mayur has never married (He feels he won’t live long anyway).

He has a girlfriend, whom he has not disclosed his status.

He has taken to smoking and alcohol

All report s normal.

CD4 count 325 cells/ml


What to do next?

1. Start ART?

2. Wait till CD4 falls upto 250 and start Septran

3. Start ayurvedic treatment or Amway products?

4. Refer?


Reassurance!! Reassurance!!!!Reassurance !!!!!!!

HIV is a chronic manageable disease like Diabetes, like Hypertension, like asthma.

One can expect a near NORMAL lifespan with HIV infected individuals

There is no cure, but with regular medicines one can lead a normal life


More than just medicines… Mental health

Diet

Hygiene-water, air

Exercise

Lifestyle

Addictions

Financial security

Disclosure / testing of partner, if indicated


Medication Dose Indication Benefit

TMP-SMX 1 DS qd CD<200 PCPToxoIsospora, cycosporaTyphoidMalariaCommunity UTI

Dapsone 1 qd CD4<200TMP_SMX HSR

PCP

Pyrimethamine 50 mg qwk CD4<200With dapsone

Toxo

Azithromycin 1.2 qwk CD4<50 MAC

INH 300 mg qd Rule out active TB MTB

Hepatitis B vaccine to all Hbs Neg

Samvad HIV Helpline 020-26381234

Chemoprophylaxis

1/19/2013

When to start ART?

All Pt with hx of AIDS-defining condition

All patients with CD4 T-cell count of <350 cells/mm3

All Pt that are pregnant, HIV nephropathy, HBV co-infection when HBV Rx is needed

Recommended for all Pt with 350-500 cells/mm3

Optional for Pt with >500 cells/mm3

DSHS,January 10, 2011


Benefits of ART The survival after development of advanced HIV

disease increased from 18 months to over 25 years for those who can access medicines.

Prevention of transmission

Secondary prevention

Post-exposure prophylaxis

Occupational and non-occupational

Mother to child transmission

Pre-exposure prophylaxis


RT

Provirus

ProteinsRNA

RNA

RT

Viral protease

Reversetranscriptase

RNA

RNA

DNA

DNA

DNA

What to start?

ZDV, ddI,ddC, d4T,3TC, ABC,TDF, FTC

DLV, NVP,EFV, ETV

SQVRTVIDVNFVfAPVLPVATVDRVTPV

ENF

Fusion

Integraseraltegravir

CCR5 antag.maraviroc


Nucleoside Reverse Transcriptase Inhibitors( NRTIs) Tenofovir (TDF)-

Zidovudine (AZT)

Lamivudine (3TC)

Emtricitabine (FTC)

Stavudine (d4T)

Didanosine (ddI)

Abacavir (ABC)

Zalcitabine (ddC)Samvad HIV Helpline 020-263812341/19/2013

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Nevirapine (NVP)

Efavirenz (EFV)

Etravirive

Delaverdine


First line regimens Preferred

TDF/XTC/EFV or NVP( Trustiva, Effoday, )

Alternative

AZT/3TC/EFV or NVP

No options available

d4T/3TC/EFV or NVP


How to monitor when on ART?1. Look for IRIS: Immune reconstitution inflammatory

syndrome

2. Look for adverse effects- clinical and lab investigations

3. Watch for drug drug interaction

4. Monitor response to ART: CD4 and Viral load


How to monitor when on ART?IRIS: Immune reconstitution inflammatory syndrome

Iris is occurrence or manifestations of new OIs within six weeks to six months after initiating ART; with increase in CD4 count

Two types: Unmasking and Paradoxical


41

IRIS

3 weeks after ART

(TDF+3TC+EFV)

Source: Dr.Rajasekaran, Superintendent, GHTM,ChennaiSamvad HIV Helpline 020-263812341/19/2013

42

IRIS

Source: GHTM,ChennaiSamvad HIV Helpline 020-263812341/19/2013

How to monitor when on ART? TDF: Renal, bone( Do urine R, S creat)

AZT: Anemia( Hb)

EFV: CNS

Nev: HSR, Hepatitis( LFT if symptomatic)

d4T: Neuropathy, lactic acidosis


Nevirapine (NVP) Rash

Hepatitis

Risk is greatest in first 6 weeks of therapy

Could be benign or fatal

Increased risk if started in women with CD4 above 250 and men with CD4 above 400

Not to use in concomitant Anti TB drugs


Nevirapine-Induced Rash

Courtesy of HIV Web Study, www.hivwebstudy.orgSamvad HIV Helpline 020-263812341/19/2013

Efavirenz Toxicity CNS Changes (excessive sleep or loss of sleep,

delusions, nightmares)

Rash

Hepatotoxicity (

Contraindicated during pregnancy

Teratogenic—Class D?

Useful in TB with HIV

Useful when stsrting ART in higher CD4 count


Long term Toxicity (After few years) Bone Marrow Suppression

Anemia

Neutropenia

Peripheral Neuropathy

Lipoatrophy

Fat accumulation

Osteoporosis

Metabolic syndrome

Myalgia

Myopathy

Pigmentation of nail beds

Lactic acidosis, fatty liver

Pancreatitis

Cardiovascular side effects

Renal dysfunction

Hepatic dysfunction


Facial Lipoatrophy


Lipodystrophy


Test On startingART

2-8 weeks after starting ART

Every 3 to 6 months

Every year

Heamogram √ √ (If on ZDV) √

Urine R √ √ (If on TDF, esp in DM, HT)

√

BSL -F √ √

ALT, AST ,S-bili √ √ √

S. creatinine √ √ √

S elec, S Ca, S Phos, Cr Cl

√ √ √

Lipid profile √ √(If last report abnormal)

√ (If last report normal)

CD4 count √ √ √( If very stable and

high counts)

Viral load √ √ √( If stable and adherent)Samvad HIV Helpline 020-263812341/19/2013

RBCs plateletsWBCs

PMNs Eos Lymphs Grans Macroph.

CD4 (T helper) CD8 (T helper) others

Knowing about CD4 Count


Uses of CD4 Cell Count Decision to initiate ARV

Guide in initiating OI prophylaxis

Assess progression of disease

Measure response to treatment (prognostication)

Detect immunologic treatment failure

Pneumocystis pneumonia

CD4 <200

TLC <1200

Toxoplasmosis

CD4 <100 and positive Toxoplasma serology

Cryptococcal meningitis

CD4 <100


CD4 COUNT Normal CD4 count is 800-1050 cells/cu.mm

CD4 decreases at a rate of 40-60 cells per yr in an HIV infected person.

Diurnal variation.

Treat OI before testing for CD4 count.

Sample :3 ml in EDTA bulb

CD4 count increases > 50 cells/mm3 at 4-8 weeks after ART and then increases an additional 50 – 100 cells / mm3 per year thereafter.

Change more than 30% is significant.

Ideally CD4 count to be measured every 6 months. Samvad HIV Helpline 020-263812341/19/2013

CD4 COUNT

148


Viral Load test of RNA PCR test Commercial methods/kits in use:

Amplicor

B-DNA

NASBA

Preferable use the same kit/ method for repeat testing

Sample :3 ml in EDTA bulb

Viral load should be below detectable level after 6 months of effective ART


Viral Load Monitoring Where available, PCR or NASBA monitoring provide

valuable information about ART effectiveness

Viral load should be checked:

Every 3-6 months when not on ART

6 months after starting ART

Every 6 -12 months in stable ART patients



Detection of Treatment Failure Immunological failure: If the CD4 cell count fail to rise,

increase < 25-50 in 1st yr, decline after previous increase; return to pre-ART baseline.

Viral load testing : Failure to achieve undetectable viral load within first 4-6 months of ART or rise after achieving a stable, low level of persistent virus

In cases of 1st line treatment failure, refer to HIV specialist.



3 years after starting ART….. Mayur has undetectable

viral load, CD4 945 cells/cu mm

No toxicity

Mayur comes with Mayuri,his girl friend who wants to marry him , pretty well knowing his positive status. She is HIV negative.


What would you ADVISE? 1. Its illegal. They cannot marry.

2. She would get infected

3. They won’t have an option of having children

4. They can marry provided they are ready to adopt safer methods.


HPTN O52: The effectiveness of antiretroviral drugs in reducing sexual transmission of HIV, by up to 96% in serodiscordant couples.

Prep trials ((iPrEx study, Partners PrEP, and TDF2, FEM-PrEP)

Circumcision : Male circumcision is associated with lower risk for HIV. May reduce female to male transmission( 50 to 60 %).


Advise for discordant couple who want to have a child If male positive

Undetectable viral load

Sperm washing with IUI

Timed intercourse with Prep

If female positive

Undetectable viral load

IUI or Timed intercourse with Prep

ART at-least from 14th weeks of pregnancy, till she stops breast feeding her child

ART drugs for newborn for 4 to 6 weeks


Mayur and Mayuri have a cute little baby girl

To test or not to test?

When to test and which tests to use?


Diagnosis in child born to HIV +ve

mother

After 18 months- Antibody tests

(Elisa/Rapid/WB)

Before 18 months- Antigen test

(HIV DNA PCR)


Advise for PPTCT ART throughout pregnancy

If viral load undetectable close to labour, no need of Caesarian section

Breast feeding advisable , but mother should continue ART

ART drugs for newborn for 4 to 6 weeks

Chances of baby getting infection below 5% .

AIDS FREE GENERATION


Ending AIDS: AIDS 2012


Will AIDS really end? Most unlikely.

No.s will fall for some time

It will restrict itself again among those who practice risky behaviour, eg People practicing risky behaviour; Sex workers; MSM

But complacency will bring it back again as our track record against any STD is poor.


2012: HIV IS STILL AN ISSUE 350 lakh people are infected with HIV worldwide

More than 96% are in low and middle income countries- in Asia

and Africa

India has 25 lakh people infected with HIV- stands third after Sub

Saharan Africa and Nigeria

Still 26 lakh new infections occur every year around the world and

18 lakh deaths from HIV/AIDS.

6000 young people are dying of HIV every

daySamvad HIV Helpline 020-263812341/19/2013

HIV estimates in India


HIV prevalence among different population groups, 2007-2008

0

1

2

3

4

5

6

7

8

MSM IDU FSW STD patients

Migrants Truckers ANC attendees

7.4 7.2

5.1

3.63.6

2.5

0.5

Source: HIV sentinel surveillance and HIV estimation in India, 2007-2008

%


So in HIV management, we as GPs are not extinct species


Thank You


Health & Medicine

HIV Update For General Practioners 2013