PEP and PrEP: AWAAC 2014

Transcription

1 Acknowledgements: HIVCS PEP guidelines group, Helen Rees, Slim Abdool Karim, Quarraisha Abdool Karim, Clinical Care Options, Edwina Wright, Jared Baeton, AETC PEP and PrEP: AWAAC 2014 Francois Venter Wits Reproductive Health and HIV Institute (RHI)

2 Post-exposure prophylaxis (PEP) Male condoms Scheckter (2002) Female Condoms Oral PrEP Grant (MSM 2010), Paxton (hetero. 2010), Baeten (2011). Treatment as Prevention Donnell (2010), Cohen (2011) HIV Prevention in 2014 HIV Counselling and Testing Behavioural Interventions Abdool Karim 2010 Microbicides for women Grosskurth (2000) STI treatment Voluntary Medical Male Circumcision Auvert (2005), Gray (2005), Bailey (2007)

3 Clinicians perceptions around their role in HIV prevention Strategies available in clinical practice (theoretically at least) Which strategies involve clinicians?

4 Ironically, it may require greater intimacy to discuss sex than to engage in it The Hidden Epidemic Institute of Medicine, 1997

5 For this talk PEP just covering the updates PrEP covering the critical stuff BUT overlap increasingly recognised

6 Source: UNAIDS

7 PEP: an update

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9 Processes.. 1 st Society guidelines published 2008 Steve Andrews/Marc Mendelsohn amalgamated occupational/ non-occupational; also 3 drugs in all exposures 2nd round 2013 requests WHO process delayed while these are finalised, due end 2014 NO DoH harmonisation

10 - or go to guidelines_nov_2008.pdf Sensible!

11 DoH Original guidelines 1993 AZT TDS, indinavir Now located in EDL still AZT/3TC Pleas for upgrade

12 Is it a problem? Huge number of traditional occupational exposures not just side effects, costs, also anxiety, burnout Other exposures bewildering array, as awareness goes up more request for PEP

13 Big thorny questions in PEP? Should I give antiretrovirals? (and high vs low risk) Should I give 2 or 3? Role of Prep?

14 Big new ideas Make peace with limited data and that we are unlikely to get better pure PEP data Occupational vs non-occupational Safe third drugs

15 Classic division: Occupational vs nonoccupational (vs PMTCT) Mucosal splashes, needlesticks, bites Helping at traffic accidents Sharing needles Sport injuries Sex worker and burst condom One night stands, cheating on partner Veno-terrorism Exposure to sex toys Cat-scratch disease The clumsy hijacker The nursery school and biting

16 Source: UNAIDS Type of exposure (HIV) Risk Needlestick 0.3% Mucous membrane 0.1% Receptive oral sex % Insertive vaginal sex <0.1% Insertive anal sex <0.1% Receptive vaginal sex % Receptive anal sex <3% Sharing IDU needle 0.7% Transfusion %

17 Anal sex 33x increase vs vaginal Uncircumcised 8x over circumcised Ulcerative 6x vs no ulcer Early infection 2.5 vs mid-point Late 1.85x vs midpoint Can climb to 1/10-1/3. Powers K, Poole C, Pettifor A, Cohen M. Rethinking the heterosexual infectivity of HIV-1: A systematic review and meta-analysis. 3rd International Workshop on HIV Transmission: Principles of Intervention. July 31-August 2, 2008, Mexico City. Abstract 14.

18 Will we give out PEP for sexual exposure? We probably should Same lessons as emergency contraception but 28 days

19 Occupational versus non-occupational WHO following our lead dumping these categories (some special occupations in new guidelines)

20 Should we give a third drug? NO data on this whether adding gives additional protection or any drug being better than the other (and we probably will never know) Adds very little to current prevention BUT Simpler, less anxiety Problem is toxicity and cost

21 Which third drug? Lop/rit safer than Ataz/rit; Darunavir/rit now an option EFV unpopular Integrase inhibitors decrease price, excellent side effect profile

22 WHO Almost all low quality evidence (except adherence!)

23 Big recommendations

24 Which drug?

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27 Likely? WHO guidelines plus Recommend integrase inhibitors as third drug (?rilpivarine, others) All usual suggestions around hepatitis B, followup etc etc

28 PrEP Pre-Exposure Prophylaxis using TDF/FTC (vaginal microbicides being explored) Controversial intervention especially in the US BUT increasing traction, especially as MSM epidemic continues Biggest challenge: adherence

29 PrEP availability July and cost QPrEP PRELUDE L Cost Truvada: A $900 month 1. Avaaz, 2014 Open label extension study New clinical trial L= licensed Demonstration study Studies closed- futility

30 Diagnoses (%) The Need for HIV Prevention: Continued HIV Risk in the US Estimated new HIV infections in the United States for the most affected subpopulations, Male-to-male sexual contact Heterosexual contact IDU Male-to-male sexual contact and IDU Other Yr CDC. HIV in the United States: 2013.

31 CAPRISA: HIV prevalence in school boys and girls in a rural South African district (grades 9 and 10) Age Group HIV Prevalence (Oct/Nov 2010) % (95% Confidence Interval) Male Female ( ) 2.2 ( ) ( ) 3.6 ( ) ( ) 7.9 ( ) ( ) 16.0 ( ) RHIVA collaboration with MiET Africa and DoE with funding from the Royal Netherlands Embassy

32 Potential types of PrEP How are the antiretrovirals used? How often are the antiretrovirals used? How many antiretrovirals are used? What antiretrovirals are used? Oral pill Topical gel (microbicide) Rectal Vaginal Injection Intravaginal ring Daily Intermittently Coitally (before/sex) Single Combination Over 25 available 32

33 So what about PrEP? Well established PMTCT Contraception, malaria prophylaxis, antibiotics if rheumatic heart disease (and often with surgery) PEP well documented and compelling

34 Subjects Reporting Unprotected Receptive Anal Sex (%) Subjects Reporting Unprotected Sex (%) PrEP Trials Found Decreasing Risk Behavior Over Time 100 iprex [1] Partners PrEP [2] Placebo TDF/FTC Placebo TDF/FTC TDF Wks Since Randomization Follow-up Time (Mos) 1. Grant RM, et al. N Engl J Med. 2010;363: Baeten JM, et al. N Engl J Med. 2012;367:

35 RCT evidence for preventing sexual HIV transmission Study Treatment for prevention (HPTN 052) PrEP for discordant couples (Partners PrEP) PrEP for heterosexuals (Botswana TDF2) Medical male circumcision (Orange Farm, Rakai, Kisumu) PrEP for MSMs (IPREX) STD treatment (Mwanza) Microbicide (CAPRISA 004 tenofovir gel) HIV Vaccine (Thai RV144) 0% % Efficacy Effect size (CI) 96% (73; 99) 73% (49; 85) 63% (21; 48) 54% (38; 66) 44% (15; 63) 42% (21; 58) 39% (6; 60) 31% (1; 51) Abdool Karim SS & Q. Lancet 2011;378:e23-5

36 Results of PrEP Trials, CDC Results from randomized, placebo-controlled, clinical trials of the efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for preventing human immunodeficiency virus (HIV) infection Clinical trial Participants Type of medication mitt efficacy* Adherence-adjusted efficacy based on TDF detection in blood Bangkok Tenofovir Injecting drug Study users Partners PrEP HIV discordant couples TDF2 iprex Fem-PrEP VOICE % (95% CI) % (95% CI) TDF 49 (10 72) 70 (2 91) TDF 67 (44 81) 86 (67 94) TDF/FTC 75 (55 87) 90 (58 98) Heterosexually active men and women TDF/FTC 62 (22 83) 84 NS Men who have sex TDF/FTC 42 (18 60) 92 (40 99) with men Heterosexually active women Heterosexually active women TDF/FTC NS NA TDF NS NA TDF/FTC NS NA Abbreviations: mitt = modified intent to treat analysis, excluding persons determined to have had HIV infection at enrollment; CI = confidence interval; TDF = tenofovir disoproxil fumarate; FTC = emtricitabine; NS = not statistically significant; NA = data not available. * % reduction in acquisition of HIV infection. Center for Disease Control. MMWR. June 14, 2013 / 62(23);

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38 CDC PrEP Guideline: For Which Patients Is PrEP Recommended? PrEP is recommended as one prevention option for the following adults at substantial risk of HIV acquisition Sexually active MSM Heterosexually active men and women Injection drug users MSM Heterosexual Women and Men Injection Drug Users Potential indicators of substantial risk of acquiring HIV infection HIV-positive sexual partner Recent bacterial STI High number of sex partners History of inconsistent or no condom use Commercial sex work HIV-positive sexual partner Recent bacterial STI High number of sex partners History of inconsistent or no condom use Commercial sex work In high-prevalence area or network HIV-positive injecting partner Sharing injection equipment Recent drug treatment (but currently injecting) CDC. PrEP Guideline

39 WHO

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41 All rely on risk assessments Clearly some will benefit: Sex workers Discordant couples MSM who are sexually active??adolescent girls?? (IDU)

42 CDC Guideline: Follow-up and Monitoring Follow-up At Least Every 3 Mos After 3 Mos and at Least Every 6 Mos Thereafter All patients Women HBsAg+ HIV test Medication adherence counseling Behavioral risk reduction support Adverse event assessment STI symptom assessment Pregnancy test (where appropriate) Assess renal function At Least Every 6 Mos Test for bacterial STIs At Least Every 12 Mos Evaluate need to continue PrEP HBV DNA by quantitative assay* *Every 6-12 mos. CDC. PrEP Guideline

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44 Practically in SA Probably start in clear high risk groups Sex workers, MSM pilot projects Discordant couples (But?utility)??Adolescent girls What should DoH do? Will it push self-testing?