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" Treatment of Co-Infections and Innovative Methods in Prevention of HIV": Prof.dr. Josip Begovac: Opening theme at the 6th Regional Conference in Sarajevo, May 17 2012.

" Treatment of Co-Infections and Innovative Methods in Prevention of HIV": Prof.dr. Josip Begovac: Opening theme at the 6th Regional Conference in Sarajevo, May 17 2012.

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  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • DSMB, data and safety monitoring board; FTC, emtricitabine; PrEP, pre-exposure prophylaxis; QD, once daily; TDF, tenofovir.
  • CI, confidence interval; FTC, emtricitabine; PrEP, pre-exposure prophylaxis; PY, person years; QD, once daily; TDF, tenofovir.
  • FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • CI, confidence interval; FTC, emtricitabine; ITT, intent to treat; PrEP, pre-exposure prophylaxis; TDF, tenofovir.
  • There was a significant effect of immediate therapy on preventing linked transmissions (those that were documented from one partner to the other). There was only 1 transmission documented in an infected partner who received earlier treatment and that transmission occurred very early after the start of therapy, almost certainly before viral load was suppressed in that patient.
  • There was also evidence of a clinical advantage in that there were fewer clinical events in the infected partner who received the earlier treatment. If we want to relate these data to our case patient, we must remember that the patients in this study had CD4+ cell counts  550 cells/mm3. However, in this group of patients, there was evidence of clinical benefit.
  • CI, confidence interval.

begovac josip  opening theme - prevention of hiv begovac josip opening theme - prevention of hiv Presentation Transcript

  • Innovative Approaches to Prevention of HIV infection Josip Begovac, Sarajevo 2012
  • HIV preventionType Level Behavioral  Individual Biomedical  Relationship (couples) Structural  Community  Societal
  • Prevention of HIV- behavioral interventions Abstinence only programs – No effect in 12 studies a negative effect in one Fewer sexual partners, faithfulness Condoms (inconsistent use) Needle exchange (coverage) Testing and counceling
  • Prevention of HIV- biomedical interventions – Circumcision (benefit for the men who are c) – Treatment of STIs = mixed results (mostly negative) – Microbicides (tenofovir gel) – Pre-exposure/post-exposure prophylaxis with antiretrovirals – Treatment of HIV (less transmission) (test and treat strategy) – Vaccine (no benefit) – Blood safety (testing)
  • Role of antiretrovirals in prevention of HIV transmission Antiretrovirals for HIV negative individuals – Before exposure (pre-exposure prophylaxis) – Oral medication – micobicide – After exposure (post-exposure prophylaxis) Antiretrovirals for HIV infected individuals – Prevention of MTCT – Prevention of sexual transmission
  • Antiretrovirals for HIV negativeindividuals
  • Pre- vs Postexposure Prophylaxis HIV HIV infection Postexposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos
  • Pre- vs Postexposure Prophylaxis HIV HIV infection Pre-exposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos
  • Pre- vs Postexposure Prophylaxis HIV HIV HIV Pre-exposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos
  • TDF and TDF/FTC for PrEP Most data in animal and human trials gained with – Tenofovir (TFV or TDF) – Fixed-dose tenofovir/emtricitabine (TDF/FTC) Trials with oral medications or vaginal gel
  • iPREX- study in MSM
  • Partners PrEP: TDF vs TDF/FTC vs Placebo in HIV-Serodiscordant Couples Follow-up: 36 mos Oral Tenofovir QD (n = 1584) HIV-negative partners in HIV-serodiscordant Oral Tenofovir/Emtricitabine QD heterosexual couples (n = 1579) (N = 4747) Oral Placebo* (n = 1584) *Placebo arm terminated early on July 10, 2011, by DSMB.Baeten J, et al. IAS 2011. Abstract MOAX0106.
  • Partners PrEP: Both PrEP Strategies Significantly Reduce HIV Acquisition Primary Efficacy TDF TDF/FTC Placebo Outcome, mITT Analysis (n = 1584) (n = 1579) (n = 1584) HIV acquisitions, n 17 13 52 HIV incidence/100 PY 0.65 0.50 1.99 Efficacy vs placebo, % 67 75 -- (95% CI) (44-81) (55-87)  P value < .0001 < .0001 --  Both PrEP strategies associated with significant reduction in HIV acquisition vs placebo in both men and women – TDF efficacy: 71% in women, 63% in men – TDF/FTC efficacy: 66% in women, 84% in menBaeten J, et al. CROI 2012. Abstract 29.
  • TDF2: PrEP With TDF/FTC in HIV- Negative Heterosexuals in Botswana ≥ 12-mo follow-up Oral Tenofovir/Emtricitabine HIV-uninfected adults, (n = 601) heterosexually active, aged 18-39 yrs (N = 1219*) Oral Placebo (n = 599) *19 patients excluded for failure to start study medication or for HIV infection.Thigpen MC, et al. IAS 2011. Abstract WELBC01.
  • TDF2: PrEP With TDF/FTC Significantly Reduces HIV Acquisition  9 vs 24 patients seroconverted in TDF/FTC vs placebo arms, respectively  Overall protective efficacy of TDF/FTC: 62.6% (95% CI: 21.5-83.4; P = .0133)  Reduction in HIV acquisition with TDF/FTC observed in both men and women but study underpowered to demonstrate sex-based differences in outcomes Time to Seroconversion (ITT Analysis) 0.10 Failure Probability 0.08 Placebo 0.06 0.04 TDF/FTC 0.02 0 0 1 2 3 YrsThigpen MC, et al. IAS 2011. Abstract WELBC01.
  • CAPRISA: Reduced HIV Incidence WithTenofovir vs Placebo Gel  Tenofovir gel associated with Tenofovir Efficacy vs Levels of Adherence decrease in HIV incidence[1] Adherence n No. of Efficacy, – 50% decrease at 12 mos Level, % Infections % – 39% decrease at 30 mos > 80 336 36 54 50-80 181 20 38 Tenofovir Placebo < 50 367 41 28 P = .007 P = .017  ↑ cervicovaginal fluid tenofovir 12 10.5 concentrations associated with ↓ HIV (Infections/100 PY) 10 9.1 seroconversion[2] Incidence Rate 8 6 5.2 5.6  No HIV resistance to tenofovir in 4 patients infected while using gel 2  Use of tenofovir gel also associated 0 Mo 12 Mo 30 with 51% decrease in HSV-2 infection[3]1. Abdool Karim Q, et al. Science DOI: 10.1126/science.1193748. 2. Kashuba A, et al. AIDS 2010.Abstract TUSS0203. 3. Abdool Karim S, et al. AIDS 2010. Abstract TUSS0204.
  • Treatment for HIV infected patients
  • PACTG 076: Results  ZDV therapy reduced risk of perinatal transmission by 67%  Excellent short-term safety 30 Transmission, % •22.6 20 10 7.6 0 Placebo ZDVSources: Connor. N Engl J Med 1994;331:1173. Sperling. N Engl J Med 1996;335:1621.
  • HPTN 052: HIV Transmission Reducedby 96% in Serodiscordant Couples Total HIV-1 Transmission Events: 39 (4 in immediate arm and 35 in delayed arm; P < .001) Linked Unlinked or TBD Transmissions: 28 Transmissions: 11 Single transmission in patient in Delayed Immediate immediate HAART arm believed Arm: 27 Arm: 1 to have occurred close to time therapy began and prior to suppression of genital tract HIV P < .001Cohen MS, et al. N Engl J Med. 2011;365:493-505.
  • HPTN 052: Analysis of Primary ClinicalEvents During Follow-up  41% reduction in HIV-related clinical events in HIV-infected patients randomized to immediate vs delayed therapy – Excess events in delayed arm driven mainly by TB (33 vs 17 cases), particularly extrapulmonary TB (17 vs 3 cases) (P = .002) 0.25 Delayed Event Probability 0.20 HR: 0.59 (95% CI: 0.40-0.88) 0.15 Immediate 0.10 0.05 0 877 701 317 86 32 25 Pts at Risk, n 886 700 333 85 36 29 0 1 2 3 4 5 Yrs Since RandomizationCohen MS, et al. N Engl J Med. 2011;365:493-505.
  • Efficacy of HIV Prevention Strategies From Randomized Clinical Trials Study Effect Size, % (95% CI) ART for prevention; HPTN 052, Africa, 96 (73-99) Asia, Americas PrEP for discordant couples; 73 (49-85) Partners PrEP, Uganda, Kenya PrEP for heterosexual men and 63 (21-84) women; TDF2, Botswana Medical male circumcision; 54 (38-66) Orange Farm, Rakai, Kisumu PrEP for MSMs; iPrEX, Americas, 44 (15-63) Thailand, South Africa Sexually transmitted diseases 42 (21-58) treatment; Mwanza, Tanzania Microbicide; 39 (6-60) CAPRISA 004, South Africa HIV vaccine; 31 (1-51) RV144, Thailand 0 20 40 60 80 100 Efficacy (%)Abdool Karim SS, et al. Lancet. 2011.
  • An Advisory Committee to the UnitedStates Food and Drug Administration(FDA) recommended the approval ofTruvada, an antiretroviral drug, for theprevention of HIV among sexuallyactive men and women (April 11 2011).The FDA is expected to make a final decision on theapproval of Truvada for the prevention of HIV byJune 15, 2012
  • Reductions in Death From Heart Disease Age-adjusted mortality Treatments Risk factors Unexplained from CHD fell by 50% in United States, 1968-1976 40 54 6 US from 1980-2000 New Zealand, 1974-1981 40 60 The Netherlands, 1978-195 46 44 10 – ~ 1/2 from risk factor United States, 1980-1990 43 50 7 reduction IMPACT Scotland, 1975-1994 35 55 10 IMPACT New Zealand, 1982-1993 35 60 5 – ~ 1/2 from treatment IMPACT England and Wales, 1981-2000 38 52 10 IMPACT United States, 1980-2000 (our 47 44 9 study) Finland, 1972-1992 24 76 IMPACT Finland, 1982-1997 23 53 24 0 50 100 Decrease in Deaths (%) Ford ES, et al. N Engl J Med. 2007;356:2388-2398.
  • Structural intervention
  • What is combination prevention? rights-based, evidence-informed, and community-owned programmes that use a mix of biomedical, behavioural, and structural interventions, prioritized to meet the current HIV prevention needs of particular individuals and communities, so as to have the greatest sustained impact on reducing new infections. UNAIDS 2010