HIV Update For General Practioners 2013

Dr Madhu Oswal
Samvad 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?

1/19/2013 Samvad HIV Helpline 020-26381234

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?


“Window Period” Following HIV Infection
Acute HIV
syndrome Antibody
Primary
HIV Asymptomatic
infection
Viremia

------------------------------------ PCR
P24 a.g
ELISA
a b
0 2 3 4 Years
1/19/2013
(Weeks since infection)
Samvad HIV Helpline 020-26381234
6
Source: S Conway and J.G Bartlett, 2003

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.


What to do?
 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


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.

Negative
Positive Uninfected

II nd Rapid / Elisa

Negative Positive
Uninfected

Symtomatic Asymptomatic

III rd Rapid / Elisa
Infected.
Negative

Equivocal W.B.

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

1/19/2013 Samvad HIV Helpline 020-26381234 Positive for

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


Chemoprophylaxis
Medication Dose Indication Benefit
TMP-SMX 1 DS qd CD<200 PCP
Toxo
Isospora, cycospora
Typhoid
Malaria
Community UTI
Dapsone 1 qd CD4<200 PCP
TMP_SMX HSR
Pyrimethamine 50 mg qwk CD4<200 Toxo
With dapsone
Azithromycin 1.2 qwk CD4<50 MAC
INH 300 mg qd Rule out active TB MTB

Hepatitis B vaccine to all Hbs Neg

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


What to start?
Fusion
ENF Viral protease
CCR5 antag.
maraviroc
SQV
RNA RNA RTV
Proteins
IDV
Reverse RT NFV
transcriptase
RNA fAPV
RNA LPV
ZDV, ddI,
DNA ATV
ddC, d4T,
RT DRV
3TC, ABC,
TPV
TDF, FTC DNA

DLV, NVP, DNA Provirus Integrase
EFV, ETV raltegravir


Nucleoside Reverse
Transcriptase Inhibitors( NRTIs)
 Tenofovir (TDF)-
 Zidovudine (AZT)

 Lamivudine (3TC)
 Emtricitabine (FTC)

 Stavudine (d4T)
 Didanosine (ddI)
 Abacavir (ABC)
 Zalcitabine (ddC) Helpline 020-26381234
1/19/2013 Samvad HIV

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


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


IRIS

3 weeks after ART
(TDF+3TC+EFV)

1/19/2013 Source: Dr.Rajasekaran, Superintendent, GHTM,Chennai
Samvad HIV Helpline 020-26381234 41

IRIS

1/19/2013 Samvad HIV Helpline 020-26381234 42
Source: GHTM,Chennai

 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.org

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  Myalgia
 Anemia  Myopathy
 Neutropenia  Pigmentation of nail
 Peripheral Neuropathy beds
 Lipoatrophy  Lactic acidosis, fatty liver
 Fat accumulation  Pancreatitis
 Osteoporosis  Cardiovascular side effects
 Metabolic syndrome  Renal dysfunction
 Hepatic dysfunction


Facial Lipoatrophy


Lipodystrophy


Test On starting 2-8 weeks after Every 3 to 6 Every year
ART starting ART months

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 √ (If last report
abnormal) normal)
CD4 count √ √ √( If very
stable and
high counts)
Viral load √ √ √( If stable and
1/19/2013 Samvad HIV Helpline 020-26381234 adherent)

Knowing about CD4 Count
WBCs RBCs platelets

PMNs Eos Lymphs Grans Macroph.

CD4 (T helper) CD8 (T helper) others


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.

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
day

HIV estimates in India


HIV prevalence among different
population groups, 2007-2008
8 7.4 7.2
% 7

6
5.1
5 3.6
4
3.6

3 2.5
2

1 0.5
0
MSM IDU FSW STD Migrants Truckers ANC
patients attendees

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

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


Thank You


HIV Update For General Practioners 2013

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HIV Update For General Practioners 2013