A.I.D.S.

A disease of human immune system

Caused by H.I.V 1 or 2

Burden- 2007

33.2 million people with AIDS2.5 million newly infected

2.1 million deaths

Transmission

Direct contact of mucous membrane or skin with infected body fluids- blood,

semen, vaginal fluid, milk

HIVAIDS

Progressive damage to CD4 +ve T-cells,

macrophages, dendritic/glial cells

Progression

Median time from HIV infection to AIDS- 9-10 years

Median survival after AIDS- 9-10 months, untreated

Effects

Increased opportunistic infection & cancers

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

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

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

Diagnosis HIV antibody p24 antigen PCR

Symptomatic person- sample reactive with 2 different kits

Asymptomatic person- sample reactive with 3 different kits

Pretreatment considerations

CD4 cell countViral load (?)

Patient’s readiness

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

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

Treatment

No cure or vaccine, yet.HAART- highly active

anti-retroviral therapy

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

Who gets HAART?

CD4 count <200CD4 count <350 in Stage III

Stage IV, irrespective of CD4

HAART regime

At least 3 drugs, belonging to 2 classes of anti-retrovirals

2NRTI + 1NNRTI/PI

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

1st line HAART

Lamivudine-150 +Zidovudine-300/Stavudine-30 +Nevirapine-200/Efavirenz-600

NNRTI preference

Nevirapine- all & pregnantEfavirenz- deranged LFT & on Rifampicin containing ATT

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 OIstop ART NSAIDssteroids

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

Side-effects of ART First few weeksN/V/D-zido./PI, Rash-NNRTI, Hepatotoxicity-NNRTI/PI,

Drowsiness/confusion-efavirenz First few monthsAnemia/neutropenia-zido., Lactic acidosis-stavudine,

Peripheral neuropathy-stavu./didano., Pancreatitis-didanosine After ~12 monthsLipodystrophy-NRTI/PI, Dyslipidemia-stavu./efavirenz/PI,

IGT/DM-indinavir

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

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

2nd line ART

Core- ritonavir boosted PIWith 2 NRTI or 1NRTI+1NNRTI

NRTI- Tenofovir, Abacavir, Didanosine

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

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

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

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