A practical approach to diagnosis and management

1. A.I.D.S.
A disease of human immune
system
Caused by H.I.V 1 or 2

2. Burden- 2007
33.2 million people with AIDS
2.5 million newly infected
2.1 million deaths

3. Transmission
Direct contact of mucous membrane or
skin with infected body fluids- blood,
semen, vaginal fluid, milk

4. HIVAIDS
Progressive damage to
CD4 +ve T-cells,
macrophages, dendritic/glial cells

5. Progression
Median time from HIV infection to
AIDS- 9-10 years
Median survival after AIDS-
9-10 months, untreated

6. Effects
Increased opportunistic infection
& cancers

7. Common OI
 TB, MAC infection
 PCP- Pneumocystis jirovecii
 Esophagitis- candida or viral
 Chronic diarrhea- bacterial, fungal, viral
 Toxoplasma encephalitis
 Cryptococcal meningitis
 Progressive multifocal leucoencephalopathy
 CMV retinitis

8. Cancers
 Kaposi sarcoma- HHV-8
 High-grade B-cell lymphoma- EBV
 Hodgkin’s lymphoma- EBV
 Primary CNS lymphoma- EBV
 Cervical/Anal cancer- HPV
 HCC- HBV/HCV

9. WHO staging
 Stage I- asymptomatic HIV infection
 Stage II- minor mucocutaneous
manifestations & recurrent URTI
 Stage III- unexplained weight loss/fever,
chronic diarrhea, severe bacterial infection,
pulmonary TB, low Hb/ANC/platelets
 Stage IV- other OI or cancers
 CDC- HIV +ve with CD4 T-cell <200
or <14% of all
lymphocytes

10. Diagnosis
 HIV antibody
 p24 antigen
 PCR
 Symptomatic person- sample reactive
with 2 different kits
 Asymptomatic person- sample reactive
with 3 different kits

11. Pretreatment considerations
CD4 cell count
Viral load (?)
Patient’s readiness

12. Pre-treatment evaluation
 HIV testing
 Risk factors & exposure
 System review- H & PE
 h/o TB, STD
 h/o pregnancy & contraception
 h/o vaccination
 Treatment history- ART & other

13. Pre-treatment lab. evaluation
 Confirm HIV
 CD4 count
 CBC, LFT
 Urine- R & M
 HBsAg & HCV Ab
 Pap smear
 Optional-
Viral load, lipid profile, CxR, pregnancy
test

14. Treatment
No cure or vaccine, yet.
HAART- highly active
anti-retroviral therapy

15. Goals of ART
 Clinical- prolongation of life &
improvement in quality of life
 Virological- greatest reduction in viral
load for as long as possible
 Immunological- immune reconstitution
 Therapeutic- rational drug use to
maximise benefit & avoid resistance
 Reduction of transmission

16. Who gets HAART?
CD4 count <200
CD4 count <350 in Stage III
Stage IV, irrespective of CD4

17. HAART regime
At least 3 drugs, belonging to
2 classes of anti-retrovirals
2NRTI + 1NNRTI/PI

18. Drugs available
 NRTI- Z,L,S,D,Z,E,A,T
 NNRTI- N,E
 PI- S,R,N,I,L/R
 Fusion inhibitors- Enfuviritide, Maraviroc
 Integrase inhibitors- Raltregavir
 Maturation inhibitors- Bevirimat, Vivecon
 CCR5 inhibitors

19. 1st
line HAART
Lamivudine-150 +
Zidovudine-300/Stavudine-30 +
Nevirapine-200/Efavirenz-600

20. NNRTI preference
Nevirapine- all & pregnant
Efavirenz- deranged LFT &
on Rifampicin containing ATT

21. Immune Reconstitution
Inflammatory Syndrome (IRIS)
 Occurrence/worsening of new/existing OI
within 6 weeks-6 months after initiating ART,
with an increase in CD4 count
 Lower the CD4 count, more likely IRIS
 Management-
 Stabilise OI, before starting HAART
 Life threatening OIstop ART
 NSAIDssteroids

22. Monitoring
 Regular counseling (adherence)
 Weight
 CD4- every 6 months
 HIV-RNA- every 6 months
 Hb- on Zidovudine
 SGPT- on Nevirapine
 RBS & lipid profile- on PI

23. Side-effects of ART
 First few weeks
N/V/D-zido./PI, Rash-NNRTI, Hepatotoxicity-NNRTI/PI,
Drowsiness/confusion-efavirenz
 First few months
Anemia/neutropenia-zido., Lactic acidosis-stavudine,
Peripheral neuropathy-stavu./didano., Pancreatitis-didanosine
 After ~12 months
Lipodystrophy-NRTI/PI, Dyslipidemia-stavu./efavirenz/PI,
IGT/DM-indinavir

24. 1st
line HAART failure
 At least after 6 months on ART
 Confirm failure-
 Clinical- new OI- stage 3 or 4, r/o IRIS
 CD4 count- persistently below 100 or fall >50% from
peak or <pre-therapy baseline after 6 months of ART
 Viral load- >1000 copies/ml
 Question adherence

25. Switch to 2nd
line ART
 CD4 &
virological failure
 WHO stage-
 1 & 2- consider switch
 3 & 4- recommend
switch
 CD4 failure
 WHO stage-
 1 & 2- don’t switch,
repeat CD4 in 3 months
 3- consider switch
 4- recommend switch

26. 2nd
line ART
Core- ritonavir boosted PI
With 2 NRTI or 1NRTI+1NNRTI
NRTI- Tenofovir, Abacavir, Didanosine

27. OI prophylaxis
 PCP- CD4<200- TMP-SMX 1 DS OD
stop when CD4>200
 Toxoplasmosis- CD4<100- TMP-SMX
stop when CD4>200
 MAC- CD4<50- Azithromycin, 1 gm OD
stop when CD4>100
 CMV retinitis- secondary only- oral Ganciclovir
stop when CD4>100
 Cryptococcal meningitis- secondary only-
Fluconazole stop when CD4>100
 Vaccination- HBV, HZV, HPV, S.pneumoniae

28. Special situations
 TB- start ATT
 CD4>350- defer ART
 CD4 200-350- ART after intensive phase ATT
 CD4<200- ART as soon as ATT is tolerated
 CLD- efavirenz, not nevirapine
 Pregnancy-
 Zido+Lami+Efavirenz (Nevirapine in 1st
TM)
 LSCS- if HIV-RNA>1000
 No ante-partum Rx-
mother-Zido+NVP, baby-Zido x6 wks ± NVP

29. Post-exposure prophylaxis
 Exposure- mild, moderate, severe
 Source- HIV +ve- symptomatic or
asymptomatic or status unknown
 Check baseline HIV, HCV, HBsAg
 Start within 2-72 hours- ideally ASAP
 PEP- Zido.+Lami.±PI (LPV/r,NLF,IND)
 Source HIV status unknown- no PEP/2 drug PEP
 Source HIV +ve- 2 or 3 drug PEP
 Duration-4 weeks
 Check HIV status- 1 & 6 months

30. Prevention
 Protected sexual intercourse- condom
 Precaution by healthcare workers to
prevent exposure to infected fluids
 Proper disposal of sharps & waste
 Needle exchange programmes for IVDU
 Perinatal treatment of mother &
newborn
 Avoid breast-feeding