Prevention and CareDr S Charalambous
www.kaizernetwork.orgwww.aids2006.orgWHO guidelines
Toronto : new information
• Kericho, Kenya : tea plantation workers - 2800 volunteers*– Circumcised 0.79/100py– Uncircumcised 2.84/100py – HRR 0.31 (95%CI 0.15 – 0.64)– (Models : Demographic factors – less significant,
Behavioural factors – still significant)• Modelling study of HIV prevalence in Soweto* in 20
years (61% protective effect)– 318 000 HIV infxns – HIV prev 16% - 23%– Current rates of circ : 17%– 10% per year –32000 fewer infections: 17% to 14% HIV prevalence– 20% per year –53000 fewer infections: 17% to 13% HIV prevalence– 30% risk behaviour – 18 000 fewer infections: 17% to 15% HIV prev
*TUAC0201 **TUAC0203
Toronto : new information Cost-effectiveness of male circumcision, J Khan*
– Orange Farm study data: Total cost: $ 56– Assumptions:
• No effect on women• 25% increased risk compensation• Life time cost of treatment $ 8000
– Cost of HIV infection averted $181 ($91 – 668 HIV Prev) Savings: $2,4 million
– Cost of circumcision must inc 45x for no cost difference
Kenya : assessment of behavioural disinhibition** following male circumcision– 648 men : 324 circumcised vs 324 uncircumcised– Baseline : Risky acts 33.6% circum vs 25.6% uncirc 0.025– No increase in sex acts or unprotected sex acts
*TUAC0203 **TUAC0205
STATE-OF-THE-ART
• Treatment naïve patients: New IAS guidelines
• Treatment experienced patients: achieving undetectable viral load
• Role of HAART in HIV prevention
Antiretroviral regimens recommended for first-line therapy (new IAS-USA guidelines)
*In selected patients #No longer recommended for initial therapy except when use of NNRTIs or PIs is precluded
Adapted from Hammer et al. JAMA 2006; 296:827-43
Recommended components
NRTI NNRTI PI
TDF + FTC ZDV + 3TC
ABC + FTC
EFV(or NVP*)
LPV/r SQV/r
ATV/r FPV/r
Alternate components
TDF + 3TC ABC + 3TC
ZDV + FTC
Special circumstances only (3-NRTI regimen)
ZDV+3TC+ABC#*In selected patients #No longer recommended for initial therapy except when use of NNRTIs or PIs is precluded
Adapted from Hammer et al. JAMA 2006; 296:827-43
Staccato: Highest response of 24-week analyses (HIV RNA < 50 copies/mL; ITT)
1. Murphy et al. AIDS 2003; 17:2603–14 2. Gathe et al. AIDS 2004; 18:1529–37 3. Podzamczer et al. 9th EACS 2003. Abstract F1/3 4. Walmsley et al. N Engl J M,ed 2002; 346:2039–46 5. van Leth et al. Lancet. 2004; 363:1253–63 6. Saag et al. JAMA 2004; 292:180–97. Staszewski et al. 10th CROI 2003. Poster 564b 8. Eron J, et al. Lancet 2006; 368: 476–829. Ananworanich et al. Antivir Ther 10: 761-7
Subjects with HIV RNA < 50 copies/mL (%)
Gilead FTC-301
0 20 40 60 80 100
StaccatoSQV/r** + 2 NRTIs
EFV + ddI + d4T
Gilead 903EFV + TDF + 3TC
Gilead FTC-301EFV + ddI + FTC
89%
Abbott 418 57%
74%78%
81%
GSK - SOLO 55%
Abbott M98-863* 65%
BMS-008*†
LPV/r (od) + FTC + TDF
FPV/r + ABC + 3TC
LPV/r + d4T + 3TC
NVP (bid) + d4T + 3TC 65%
ATV + d4T + 3TC 38%
2NN*
KLEAN*LPV/r + ABC + 3TC 72%KLEAN*FPV/r + ABC + 3TC 68%
† ATV 400 mg results used; *HIV RNA at 24 weeks estimated from graph; **Investigational Invirase/r 1600/100 mg qd dosage. The approved dosing regimen is Invirase/r 1000/100 mg bid
Tenofovir
• 903 Trial: 96 week results: safety and tolerability of tenofovir,
• Uganda: reduction in side effects due to tenofovir
• Subtype C isolates may develop the K65R mutation more rapidly than Subtype B isolates
• Uganda & Zimbabwe: 1.3% patients developed severe GFR reduction, found to have similar rates of glomerular filtration reduction as other regimens
Treatment-experienced patients
• Undetectable viremia is now a realistic goal of therapy for treatment-experienced patients
• Before adding a new agent, ARVs should be selected to provide the maximum activity – Baseline characteristics are important prognostic
factors predictive of a treatment response– Resistance testing may overestimate the number
of active drugs– Drugs from a new mechanistic class (e.g. ENF)
should retain their full activity in treatment-experienced patients
30%
60%
< 400 copies/mLWeek 24
Pat
ien
ts (
%)
TORO 1 & 2
LPV/rLPV/r + ENF
46%
64%
< 50 copies/mLWeek 24
Pat
ien
ts (
%)
POWER 1 & 2
DRV/rDRV/r + ENF
30%
54%
Pat
ien
ts (
%)
RESIST 1 & 2
TPV/rTPV/r + ENF
< 400 copies/mLWeek 24
Haubrich et al. IDSA 2005; Abstract 785; Hill and Moyle. BHIVA 2006; Abstract P1.
Summary of TORO, RESIST and POWER trials
HAART and HIV Prevention
• PMTCT works by reducing viral load to reduce transmission
• Uganda, Quinn et al – reduction of transmission in serodiscordant couples – no transmission if VL<1500
• Taiwan, reduction in HIV transmission 53% after introduction of HAART
• Call for cost-effectiveness of use of HAART as prevention : immediate treatment of 100% HIV population– Cost $7 billion/year – total cost $42 billion– HIV infected people 38 million to <1 million
• “History will judge us not by our scientific advances, but what we do with our scientific advances” A Fauci