Lessons from MSM PrEP pilots / demonstration projects. Kevin Rebe

Transcription

1 Lessons from MSM PrEP pilots / demonstration projects Kevin Rebe rebe@anovahealth.co.za

2 PrEP Demonstration Projects US: Multisite demonstration project in San Francisco, Miami and Washington DC. South America: PrEP Brasil South Africa: TAPS project for SW in Jhb and EJAF PrEP for MSM in CT and Jhb

3 US PrEP Demonstration Project Launched Sep 2012, fully enrolled Mar 2014 Eligible: At risk, HIV and HBV negative Fuchs, J et al. Lessons learned from the US PrEP Demonstration Project: Moving from the real world to the real, real world. content/uploads/2015/04/fuchs-fapp-15-april- 15.pdf

4 US PrEP Demonstration Project Lui A et al. Adherence, sexual behavior and HIV/STI incidence among MSM and TGW in the US PrEP Demonstration Project. Abstract IAS Vancouver, Canada.

5 US PrEP Demo Project HIV Infections Enrolment 3 Follow up 2 (wk 19 and 48) M184V Mutation 1 No Resistance Mutations 2 No Resistance Mutations 2 Fuchs, J et al. Lessons learned from the US PrEP Demonstration Project: Moving from the real world to the real, real world.

6 First Demo in LMIC PrEP uptake associated with: City / site of delivery TG versus male High perceived HIV risk Previous HIV testing Previous PrEP awareness >2 Condomless RAI partners Sex with HIV pos partners Grinsztejn, B et al. PrEP Uptake and associated factors among MSM and TGW in the PrEP Brazil demonstration project. Abstract. IAS 2015 Vancouver, Canada.

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8 PrEP Works For High-risk People Subgroup analyses of PrEP trials show that PrEP is effective for those at greatest HIV risk: Heterosexuals (Partners PrEP) Murnane et al. AIDS 2013 Reporting sex without condoms With an STI With an HIV+ partner who has a high plasma HIV viral load Women <30 years of age MSM (iprex) Buchbinder et al. Lancet ID 2014; Solomon et al. Clin Infect Dis 2014 Used cocaine Had syphilis Had anal sex with an HIV+ partner HIV protection estimates for these subgroups were often higher than for the trial population as a whole, because adherence was often greater for persons taking greater risks

9 Concerns About PrEP for MSM ARV resistance Risk compensation Adherence Toxicity Roll out / Scale up

10 The EJAF PreP Demonstration Project for MSM The South African PrEP Demonstration Project Demonstration project not a clinical study Running within Health4Men COE s Aims: Assess feasibility of delivering nurse-driven PrEP at a primary health care level as part of combination HIV prevention Recruit 300 MSM at two sites (CT and Jhb) and maintain on PrEP over two years >125 recruited to date 1 lost to follow up at month 2.

11 The EJAF PreP Demonstration Secondary Aims: Project for MSM Assess the knowledge, acceptability and uptake of PrEP and other HIV prevention interventions among HIV-negative MSM Characterize the population of MSM who accept PrEP Assess retention in the study at 3, 6, 9 and 12 months. Monitor patterns of use of PrEP. Assess prevention method preferences and acceptability. Monitor side effects and safety of PrEP. Monitor the HIV status of MSM using PrEP and the emergence of drug resistance among those who acquire HIV. Monitor changes in self-reported sexual behaviour in MSM (including reduction or increase of risky sexual behaviour). Assess adherence to PrEP medications using therapeutic drug level monitoring

12 Regulatory Hurdles Ethics and state research committees Project predated MCC registration of PrEP Submitted as a clinical trial Full informed consent and GCP procedures No participant reimbursement Approval granted for experimental medicines TDF/FTC ànurse prescribing

13 PrEP and ARV Resistance Resistance from PrEP was very rare, with only a small number who had acute infection at the time they were started on PrEP. Partners PrEP # of HIV seroconverters assigned PrEP with HIV resistance HIV infected after enrollment Seronegative acute HIV infection at enrollment 0 / 48 2 / 10 What Happens in African MSM? iprex 0 / 36 2 / 2 Background TDF resistance rates unknown Cause for alarm? TDF2 0 / 10 1 / 1 Do we need an alternative drug? Resistance = K65R (TDF) or M184V/I (FTC) mutations

14 Risk compensation in PrEP clinical trials In both iprex and Partners PrEP, unprotected sex and STIs were less common over time suggesting synergy of ongoing riskreduction counseling along with PrEP. TDF FTC/TDF Placebo iprex Proportion of HIV participants with any unprotected sex (%) Partners PrEP ACASI behavioural questionnaire Study Month

15 Perfect Adherence is Not Required: iprex OLE d HIV 100% HIV protection was seen with adherence consistent with 4 tablets per week Grant et al. Lancet ID 2014

16 Asymptomatic STIs Syphilis Hepatitis and other sexual viruses HIV The majority of gonorrhoea and chlamydia are symptomatic in KPs (non-urethral sites) EJAF PrEP Rapid HIV Rapid syphilis Clinical history and exam Point of care testing absent... ASTI Treatment Guidelines CDC (and various USA & EU guidelines) Yearly syphilis PCR screening of pharynx, anus and urethra based on sexual history WHO: Presumptive STI treatment for at risk MSM Reported UAI in the last year PLUS Partner with an STI OR Multiple partners

17 The Empiric Syndromic Approach To STI Treatment Syndromic treatment of STIs advocates: New Syndromic Guidelines: Treatment according to syndromes (e.g. discharge Replace cefixime with ceftriaxone / ulcer / nodule / rash) Replace doxycycline with azithromycin No collection of samples for lab analysis This is the current approach advocated by the SA Department of Health. Not addressing STIs among MSM on PrEP No syndrome if asymptomatic No determination of GC resistance Little consideration of non-urethral infection sites

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19 Implementation Lessons Level of monitoring PrEP Demo Project Monitoring: Two HIV neg tests two weeks apart Baseline creatinine and baseline HBV screen Creatinine at month 1, 2 and 3 monthly HCT at month 1,2 and 3 monthly TDF blood levels at month 1,2 and 3 monthly à Not feasible or necessary à No late creatinine elevation identified to date in demo project à Not all had positive TDF blood level at month 1 (>85%) à SA Clinician Society Guidelines more than sufficient

20 Implementation Lessons Nurses are able to provide PrEP Required extensive training (3 days) Require detailed operational manuals and tools Require oversight and mentoring especially in the first month Able to educate and provide correct information Adherence assessment and support challenging Designing an adherence support package that can be implemented by nurses in <15 minutes Adapt existing tools and using next step counselling Train current lay counsellors Leverage virtual support

21 Implementation Lessons Demand Creation Political will Civil society support (SANAC) Education and knowledge translation Outreach and peer programs Marketing Demand has been higher than our planned recruitment rate

22 Today s News 125 recruited 1 known not to have started PrEP (LTFU) 2 known to have cycled off 2 stopped due to worsening renal parameters Word of mouth is main referral route Impression that predominantly gay-identified Second site trained and ready launch once staff and logistics confirmed

23 Funding PrEP Putting in the plug Treatment Linkage to care Better programs Support etc Turning off the tap Treatment Condoms and lube PEP PrEP Incidence is rising in MSM All those who are positive will need lifelong (expensive) ART + monitoring Proud: PrEP for 13 MSM prevents 1 HIV infection IPERGAY: PrEP for 18 MSM prevemts 1 HIV infection à Front load investment for long term benefits à Accurate investment case for Ministries of Health

24 How to Sell PrEP?

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27 Thank You SA Clinicians Society PEPFAR / USAID Elton John Foundation Anova Health Institute Contact: Kevin Rebe rebe@anovahealth.co.za Ben Brown bbrown@anovahealth.co.za