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Prevention and Care Dr S Charalambous kaizernetwork aids2006 WHO guidelines

Prevention and Care Dr S Charalambous www.kaizernetwork.org www.aids2006.org WHO 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)

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Prevention and Care Dr S Charalambous kaizernetwork aids2006 WHO guidelines

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  1. Prevention and Care Dr S Charalambous www.kaizernetwork.org www.aids2006.org WHO guidelines

  2. 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

  3. 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

  4. STATE-OF-THE-ART • Treatment naïve patients: New IAS guidelines • Treatment experienced patients: achieving undetectable viral load • Role of HAART in HIV prevention

  5. 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 *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

  6. Staccato: Highest response of 24-week analyses (HIV RNA < 50 copies/mL; ITT) 38% ATV + d4T + 3TC BMS-008*† 55% FPV/r + ABC + 3TC GSK - SOLO 57% LPV/r (od) + FTC + TDF Abbott 418 65% LPV/r + d4T + 3TC Abbott M98-863* 65% NVP (bid) + d4T + 3TC 2NN* 68% FPV/r + ABC + 3TC KLEAN* 72% LPV/r + ABC + 3TC KLEAN* 74% EFV + ddI + d4T Gilead FTC-301 78% EFV + TDF + 3TC Gilead 903 81% EFV + ddI + FTC Gilead FTC-301 89% SQV/r** + 2 NRTIs Staccato 0 20 40 60 80 100 Subjects with HIV RNA < 50 copies/mL (%) † 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 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; 292:180–9 7. Staszewski et al. 10th CROI 2003. Poster 564b 8. Eron J, et al. Lancet 2006; 368: 476–82 9. Ananworanich et al.Antivir Ther 10: 761-7

  7. 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

  8. 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

  9. Summary of TORO, RESIST and POWER trials POWER 1 & 2 TORO 1 & 2 RESIST 1 & 2 64% 60% 54% 46% Patients (%) Patients (%) Patients (%) 30% 30% < 50 copies/mL Week 24 < 400 copies/mLWeek 24 < 400 copies/mL Week 24 LPV/r TPV/r DRV/r LPV/r + ENF TPV/r + ENF DRV/r + ENF Haubrich et al. IDSA 2005; Abstract 785; Hill and Moyle. BHIVA 2006; Abstract P1.

  10. 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

  11. “History will judge us not by our scientific advances, but what we do with our scientific advances” A Fauci

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