Ephraim Sakala1, Chepela Ngulube1, Sandra Simbeza1, Martin. Mutonyi1, Sarah Fidler3 ... London, United Kingdom, 4London School of Hygiene &. Tropical ...
use starts in 2014. We considered different efficacy and coverage scenarios for PrEP. Results: Our model projections suggest that with existing interventions, FSW HIV prevalence is on the decline in Calcutta. The different PrEP intervention scenarios suggest that PrEP use could result in rapid and substantial decreases in HIV prevalence and incidence compared to the baseline scenario of no PrEP, with a 60% reduction in HIV incidence achievable over 20 years with a PrEP efficacy of 60% and coverage of 60%. However, the efficiency of PrEP is low with about 40 years of PrEP being required per life year gained in the most optimistic PrEP scenario (60% coverage and efficacy). Conclusions: PrEP interventions could be important for controlling HIV in FSW driven epidemics in Calcutta and India in general, but may not be cost-effective in many scenarios.
OA27.05 The Potential Impact of Long-acting PrEP on HIV Transmission, Mortality and Drug Resistance in KwaZulu-Natal, South Africa: Model-based Analyses Robert Glaubius1, Greg Hood2, Ume Abbas1 1 Cleveland Clinic, Infectious Disease and Quantitative Health Sciences, Cleveland, OH, United States, 2Pittsburgh Supercomputing Center, Pittsburgh, PA, United States
Background: Long-acting injectable rilpivirine (RPV) preexposure prophylaxis (PrEP) could be pivotal for optimizing PrEP effectiveness for HIV prevention. The impact of RPV PrEP on HIV transmission, mortality and the spread of drug resistance are unknown. Methods: We examine the scale-up of RPV PrEP, ART and male medical circumcision (MMC) using a mathematical model of the HIV epidemic in KwaZulu-Natal (KZN). We compare a baseline scenario of ART and MMC scaled up to 80% coverage by 2017 to three scenarios of ART and MMC plus ten years of PrEP (90% efficacy; 35% cross-resistance) rollout starting in 2015: a) 10% overall coverage of susceptible adults (20% of KZN’s HIV budget at $165 per person-year of PrEP), either unprioritized or b) prioritized to women aged 20–29; or c) 80% coverage of high-risk adults (< 2% of the HIV budget).
Outcomes include infections averted and drug resistance prevalence over ten years, and lifetime life-years (LY) lived, cost and cost-effectiveness. We classify scenarios as very cost-effective if the incremental cost per LY saved is less than South Africa’s per capita GDP of $7,500, and cost-saving if costs decrease while life-years increase. Results: Unprioritized PrEP averts 6.8% of infections over ten years and saves 1.9 million LY in the PrEP-exposed cohort ($605/LY saved). Age-prioritization improves PrEP’s impact, averting 12.6% of infections and saving 3.5 million LY ($113/ LY saved). Risk-prioritized PrEP reduces costs by 0.7%; it averts more infections (8.4%) and saves more LY (2.3 million) than unprioritized PrEP while using < 10% as many person-years of PrEP. Drug resistance decreases with unprioritized or ageprioritized PrEP (1%; 1.7%), and increases by 2.5% with riskprioritized PrEP compared to baseline (358,000 cases at 2025). Conclusions: RPV PrEP is potentially very cost-effective, and may be cost-saving when prioritized to high-risk persons. Drug resistance from PrEP is limited compared to ART, though riskprioritized PrEP may increase overall resistance.
OA27.06 LB A Phase 1 Open Label Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Intramuscular TMC278 LA (the MWRI-01 Study) Ian McGowan1, Aaron Siegel2, Kathy Duffill2, Cory Shetler2, Charlene Dezzutti1, Nicola Richardson-Harman3, Kaleab Abebe1, David Back4, Laura Else4, Amy Herrick5, Peter Williams6, Khaja K Rehman2, Ross D. Cranston1 1
University of Pittsburgh School of Medicine, Pittsburgh, PA, United States, 2Magee Women Research Institute, Pittsburgh, PA, United States, 3Alpha StatConsult LLC, Damascus, MD, United States, 4University of Liverpool, Liverpool, United Kingdom, 5University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, United States, 6Janssen Research and Development, Beerse, Belgium Background: Long acting (LA) injectable antiretroviral agents are being evaluated as a potential strategy for pre-exposure prophylaxis of HIV infection. This study was undertaken to characterize the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of TMC278 LA. Methods: Healthy HIV-1 seronegative participants were enrolled into 2 cohorts. 12 women and 6 men received an intramuscular dose of either 1200 mg (Cohort 1; N = 18) or 600 mg (Cohort 2: N = 18) of TMC278 LA. Plasma and tissue (rectal [RT], cervical [CT], and vaginal [VT]) were collected before and after exposure to TMC278 LA. Participants were followed for 4 months after receiving TMC278 LA. Safety, acceptability, multicompartmental PK, and PD (ex-vivo explant challenge with HIV-1BaL) were monitored throughout the study. Results: Thirty six participants were enrolled. There were 183 adverse events of which 179 (97.8%) were Grade 1/2. Two Grade 3 and 2 Grade 4 events were unrelated to study product. The mean acceptability score was 7 out of a maximum of 10. Geometric mean (GM; 90% CI) plasma TMC278 concentrations at Day 28 post-dose for the 1200 mg and 600 mg cohorts were 53 (38–67) ng/mL (female) / 43 (23–63) ng/mL (male) and 28 (19–37) ng/mL (female) / 17 (9–24) ng/mL (male) respectively. For the 1200 mg dose the GM tissue: plasma ratios at Day 28 were 0.68 (VT), 0.77 (CT), 1.21 (female RT), and 1.27 (male RT). Exposure to TMC278 LA was associated with significant suppression of viral replication in RT (p < 0.0001) that persisted for up to four months following exposure to TMC278 LA, but viral suppression was not seen in VT or CT. Conclusions: Single dose administration of TMC278 LA was safe and well tolerated with dose dependent plasma PK exposure. The TMC278 tissue: plasma ratio for RT was approximately two-fold higher than VT or CT. This is the first study to demonstrate prolonged suppression of explant viral replication following systemic antiretroviral exposure. Multiple dosing studies of TMC278 LA are planned.
Treating and Preventing: The Role of ARVs OA28.01 High Initiation and Adherence among High Risk African HIV Discordant Couples in a Demonstration Project of PrEP and ART for HIV Prevention Renee Heffron1, Connie Celum1, Nelly Mugo2, Elly Katabira3, Elizabeth Bukusi2, Stephen Asiimwe4, Kenneth Ngure5, Nulu Bulya3, Josephine Odoyo2, Edna Tindimwebwa4, Deborah Donnell6, Jessica E. Haberer7, Lara Kidoguchi1, Jennifer Morton1, Jared M. Baeten1, for the Partners Demonstration Project Team
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University of Washington, Global Health, Seattle, WA, United States, 2Kenya Medical Research Institute, Nairobi, Kenya, 3 Makerere University, Kampala, Uganda, 4Kabwohe Clinical Research Center (KCRC), Kabwohe, Uganda, 5Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya, 6 Fred Hutchinson Cancer Research Center, Seattle, WA, United States, 7Massachusetts General Hospital, Boston, MA, United States Background: Pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) have high efficacy for HIV prevention among heterosexual African HIV discordant couples. Assessing initiation and adherence to antiretroviral-based HIV prevention strategies outside of clinical trial settings is a priority. Methods: Enrollment of high-risk HIV discordant couples into an open-label PrEP and ART demonstration project in Kenya and Uganda began in November 2012. Without PrEP and ART, anticipated HIV incidence in this cohort would be ‡ 5% per year. ART is offered per national guidelines and PrEP is offered as a ‘bridge’ to ART, provided between study enrollment and the time when the HIV-infected partner is likely to have achieved viral suppression. ART adherence is assessed through biannual HIV RNA measurements and MEMS caps are used to assess PrEP adherence. Results: As of April 2014, 714 high risk couples were enrolled, 67% with an HIV infected woman, and 42% with an HIV infected partner eligible to initiate ART. At enrollment, 96% of HIV uninfected participants initiated PrEP and 92% of ARTeligible participants planned to start ART. To date, 51% of couples have had ‡ 6 months of expected follow-up and retention through 6 months is 88% for HIV uninfected and 93% for infected participants. Among HIV uninfected participants on PrEP, 77% took ‡ 80% of expected PrEP doses by MEMS between enrollment and their 6 month clinic visit. Travel and relationship dissolution are common reasons for missing PrEP doses, reported at 27% and 18% of visits with missed doses. Among HIV infected participants initiating ART at enrollment, 85% had a plasma HIV RNA concentration < 400 copies/ml by the 6 month visit. Six months after enrollment, 85% of couples were using PrEP and/or ART: 45% PrEP only, 14% ART only, and 26% both PrEP and ART. Conclusions: PrEP and ART initiation and early adherence are high among high-risk African HIV discordant couples participating in an open-label demonstration project of PrEP and ART for HIV prevention.
Background: Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) significantly reduce HIV transmission within heterosexual HIV serodiscordant couples. To maximize impact and minimize costs, ART and PrEP interventions should be offered to couples at highest risk of HIV transmission. Methods: The Partners Demonstration Project is an open-label, prospective cohort study of PrEP and ART for HIV prevention among high risk HIV serodiscordant couples in Kenya and Uganda. We evaluated the feasibility of using a validated empiric risk score (Kahle et al. JAIDS 2013) that uses a combination of variables (age, number of children, male circumcision status, plasma HIV levels, condom use, marital status) to identify couples at highest risk for HIV transmission. Results: Since November 2012, 1217 couples have screened and 714 enrolled. Of the screened couples, 274 (23%) scored 0–4 (anticipated HIV incidence of £ 2% per year), 493 (41%) scored 5–6 (anticipated HIV incidence of *5% per year) and 450 (37%) scored ‡ 7 (anticipated HIV incidence of ‡ 7% per year). Couples scoring ‡ 5 were eligible for enrollment and 76% entered the study. The median age of the HIV uninfected partner was 29.5 [IQR 26, 36] years and the HIV seronegative partner was male in 67% of partnerships. Over half (57%) had no children, 92% had unprotected sex in the month prior to screening and 34% of HIV susceptible men were uncircumcised. Among HIV infected members of the couples, the median CD4 count was 436 [IQR 274,634] cells/mm3 and 41.3% had a plasma viral load > 50,000 copies/ml. Conclusions: An empiric risk score derived from observational analyses of African HIV serodiscordant couples identified higher risk HIV discordant couples for a demonstration project of PrEP and ART for HIV prevention. Three-quarters of the higher risk couples who were eligible have enrolled. Risk scores could be useful for recruitment of higher risk persons and couples into future HIV prevention trials and demonstration projects.
OA28.03 Facing the Realities of HIV Universal Test and Treat: Early Lessons Learned from the Delivery of the HPTN071/ PopART Study Intervention in Zambia Kwame Shanaube1, Sam Griffith2, Musonda Simwinga1, Ephraim Sakala1, Chepela Ngulube1, Sandra Simbeza1, Martin Mutonyi1, Sarah Fidler3, Richard Hayes4, Helen Ayles1,5, HPTN071-PopART study Team 1
OA28.02 Evaluation of a Risk Score Tool to Identify Higher-risk HIV-1 Serodiscordant Couples for Antiretroviralbased HIV-1 Prevention Elizabeth M. Irungu1, Renee Heffron2, Nelly Mugo2,3, Kenneth Ngure2,4, Elly Katabira5, Nulu Bulya5, Elizabeth Bukusi2,3, Josephine Odoyo3, Stephen Asiimwe6, Edna Tindimwebwa6, Deborah Donnell2,7, Connie Celum2, Jared M. Baeten2, Partners Demonstration Project Team 1
Kenyatta National Hospital, Nairobi, Kenya, 2University of Washington, Seattle, WA, United States, 3Kenya Medical Research Institute, Nairobi, Kenya, 4Jomo Kenyatta University of Agriculture and Technology, Ruiru, Kenya, 5Makerere University, Kampala, Uganda, 6Kabwohe Clinical Research Center (KCRC), Kabwohe, Uganda, 7Fred Hutchinson Cancer Research Center, Seattle, WA, United States
ZAMBART Project, Lusaka, Zambia, 2FHI 360, Science Facilitation Department, Washington, NC, United States, 3Imperial College, Department of Infectious Disease Epidemiology, London, United Kingdom, 4London School of Hygiene & Tropical Medicine, Department of Infectious Disease Epidemiology, London, United Kingdom, 5London School of Hygiene & Tropical Medicine, Department of Clinical Research, London, United Kingdom Background: The HPTN071 (PopART) is a 5-year community randomized study of a combination HIV prevention package in 21 communities in Zambia and South Africa. HPTN071 is one of the first studies to evaluate a combined HIV prevention package (including universal HIV testing and ART for all HIV + individuals irrespective of CD4 count (UTT)) on HIV incidence at community-level. Methods: 21 communities were randomly assigned to one of three study arms. The study intervention consists of door to door
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