CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

868 Rare Incidence of Proximal Tubular DysfunctionWith Tenofovir-Based Chemoprophylaxis Kenneth K. Mugwanya 1 ; Jared M. Baeten 1 ; Connie M. Celum 1 ; Deborah Donnell 2 ;Thomas Nickolas 3 ; Nelly R. Mugo 4 ; Andrea Branch 5 ; James K. Kairie 6 ; Allan Ronald 7 ; ChristinaWyatt 5 ; for the Partners PrEP StudyTeam 1 Univ of Washington, Seattle, WA, USA; 2 SCHARP, Fred Hutchinson Cancer Rsr Cntr, Seattle, WA, USA; 3 Columbia Univ, New York, NY, USA; 4 Kenya Med Rsr Inst, Thika, Kenya; 5 Icahn Sch of Med at Mount Sinai, New York, NY, USA; 6 Univ of Nairobi, Nairobi, Kenya; 7 Univ of Manitoba, Winnipeg, MB, Canada Background: Tenofovir disoproxil fumarate (TDF) is infrequently associated with proximal tubular dysfunction in HIV-infected persons when used as part of combination antiretroviral therapy, but limited data are available for HIV-uninfected persons on TDF for pre-exposure prophylaxis (PrEP). Methods: Data are from the Partners PrEP study, a randomized trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African HIV-uninfected men and women (ClinicalTrials.gov:NCT00557245). We conducted: 1) a cohort analysis to determine whether FTC-TDF PrEP causes proximal tubular dysfunction among HIV-uninfected persons randomized to FTC-TDF versus placebo, and 2) a nested case-control analysis of persons on TDF or FTC-TDF to determine whether tubular dysfunction predicts subsequent clinically relevant decline in estimated glomerular filtration rate (eGFR). The primary outcome was subclinical proximal tubulopathy (PT), pre-defined as any two of the following markers of tubular dysfunction: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate excretion, or increased urinary uric acid excretion. PT was assessed in concurrently obtained urine and serum samples at the 24-month visit or last on-treatment visit. For the nested case-control analysis, cases were persons on TDF or FTC-TDF with confirmed ≥25% eGFR decline from baseline and controls were persons with similar drug exposure without the ≥25% eGFR decline. Results: Of 1549 persons included in the cohort (776 on FTC-TDF, and 773 on placebo), 64%were male. Median age was 37 years (range 18-64) and median duration of study drug exposure was 24 months (range 3-27). The frequency of PT was 1.7% in FTC-TDF versus 1.3% in the placebo arm [odds ratio 95% confidence interval: 1.30 (0.52, 3.33); p=0.68]. PT occurred in 2 of 52 (3.8%) persons who experienced ≥25% eGFR decline versus 3 of 208 (1.4%) controls (adjusted odds ratio, 95% confidence interval: 1.40 (0.10, 14.1); p >0.99]. One person on FTC-TDF and potentially nephrotoxic co-medications developed features indicative of Fanconi syndrome. Conclusions: In this large placebo-controlled study, proximal tubular dysfunction was rare and was not significantly associated with daily oral FTC-TDF PrEP over up to 24 months of observation, nor did it predict a subsequent clinically relevant decline in eGFR. These findings support the safety of TDF-based PrEP as a component of HIV prevention in healthy HIV-uninfected individuals. 869 STI Data From Community-Based PrEP Implementation Suggest Changes to CDC Guidelines Sarit A. Golub 1 ; Stephanie Pena 2 ; Kailip Boonrai 3 ; Nora Douglas 2 ; Machel Hunt 2 ; Asa Radix 2 1 Hunter Coll and the Grad Cntr, City Univ of New York, New York, NY, USA; 2 Callen-Lorde Community Hlth Cntr, New York, NY, USA; 3 Hunter HIV/AIDS Rsr Team, Hunter Coll, New York, NY, USA Background: Current CDC Clinical Practice Guidelines for the provision of pre-exposure prophylaxis (PrEP) recommend screening for sexually transmitted infections (STI) only every 6 months, unless patients report symptoms. CDC’s 2015 STD Treatment Guidelines recommend STI screening for MSM every 3-6 months, but emphasize testing those with past STI history. Methods: SPARK is a community-based PrEP demonstration project conducted at the largest LGBT health center in New York City. Patients prescribed PrEP are screened for urethral/rectal gonorrhea and chlamydia as well as syphilis every 3 months, and also visit the clinic for STI testing and treatment between study visits if they experience symptoms. STI data for patients in the 6-months prior to starting PrEP and in their first 12-months taking PrEP were abstracted from electronic medical records (EMR). We examined: a) the number and type of STIs that were diagnosed at each time point; b) diagnosis due to symptomatic patient presentation versus routine screening; and c) whether or not a positive STI at a previous time point would have triggered asymptomatic screening (absent the SPARK study protocol). Results: Among the 280 patients who began PrEP, 21% (n = 58) had an STI in the 6-months prior to starting PrEP (including 11%who tested positive for an STI at their PrEP prescription visit). At 3-month follow-up, 13% of patients were diagnosed with STIs, with 77% of these cases (10% of the total sample) resulting from routine screening, rather than symptomatic presentation. In addition, only 33% of patients with STIs at 3-month follow-up had a prior history of STI that would have triggered screening. At 9-month follow-up, 15% of patients were diagnosed with STIs, with 68% (10% of the total sample) diagnoses as a result of routine rather than symptomatic screening. Even though the percentage of patients with repeat STI diagnoses increased over time, basing STI screening on prior diagnosis at the 9-month visit would have missed 16% of STI cases. Overall, STI screening according to current CDC guidelines would have delayed diagnosis and treatment for 24% of PrEP patients, including 40 cases of rectal STI and 3 cases of syphilis. Conclusions: Current CDC guidelines may miss a significant number of asymptomatic STI among PrEP users. STI screening may be particularly important at the first 3-month follow-up visit. Routine STI testing at each PrEP prescription visit appears warranted, with particular attention to those with past STI history.

Poster Abstracts

870 Quarterly STI Screening Optimizes STI Detection Among PrEP Users in the Demo Project

Stephanie Cohen 1 ; EricVittinghoff 2 ; Susan S. Philip 1 ; Susanne Doblecki-Lewis 3 ; Oliver Bacon 1 ;Wairimu Chege 4 ; Richard Elion 5 ; Susan P. Buchbinder 1 ; Michael Kolber 3 ; AlbertY. Liu 1 1 San Francisco Dept of PH, San Francisco, CA, USA; 2 Univ of California San Francisco, San Francisco, CA, USA; 3 Univ of Miami, Miami, FL, USA; 4 DAIDS, NIAID, NIH, Bethesda, MD, USA; 5 George Washington Univ Sch of Med, Washington, DC, USA Background: Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but does not protect against sexually transmitted infections (STIs). The US CDC recommends that men who have sex with men (MSM) on PrEP be screened for STIs every 6 months. Among a cohort of participants in a PrEP demonstration project, we assessed: 1) the number and percent of gonorrhea (GC) and chlamydia (CT) infections that would have been missed if extra-genital screening had not been conducted and 2) The number and percent of participants infected with GC, CT or syphilis for whom treatment would have been delayed without quarterly screening. Methods: MSM and transgender women participating in an open-label PrEP demonstration project were tested for syphilis and urethral (U), pharyngeal (P) and rectal (R) GC and CT at screening and at weeks 12, 24, 36 and 48, and treated promptly if positive. Participants were considered asymptomatic if they denied STI symptoms on a structured review of symptoms and did not have any signs on physical examination. To determine the number of infections that would have been missed without extra-genital screening, we calculated the number and proportion of R and P GC and CT infections in which there was not a concurrent U GC or CT infection. To determine the number of participants with GC, CT or syphilis

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CROI 2016