Prevention and Care Dr S Charalambous WHO guidelines

Toronto : new information Kericho, Kenya : tea plantation workers 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) – 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 – 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 –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: Recommended components NRTINNRTIPI 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; 17:2603–142. Gathe et al. AIDS 2004; 18:1529–37 3. Podzamczer et al. 9th EACS Abstract F1/34. Walmsley et al. N Engl J M,ed 2002; 346:2039–46 5. van Leth et al. Lancet. 2004; 363:1253–636. Saag et al. JAMA 2004; 292:180–9 7. Staszewski et al. 10 th CROI Poster 564b8. Eron J, et al. Lancet 2006; 368: 476–82 9. Ananworanich et al. Antivir Ther 10: Subjects with HIV RNA < 50 copies/mL (%) Gilead FTC Staccato SQV/r** + 2 NRTIs EFV + ddI + d4T Gilead 903 EFV + TDF + 3TC Gilead FTC-301 EFV + ddI + FTC 89% Abbott % 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/mL Week 24 Patients (%) TORO 1 & 2 LPV/r LPV/r + ENF 46% 64% < 50 copies/mL Week 24 Patients (%) POWER 1 & 2 DRV/r DRV/r + ENF 30% 54% Patients (%) RESIST 1 & 2 TPV/r TPV/r + ENF < 400 copies/mL Week 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