CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: 18 patients identified; 17 male/1 female, mean age 34 years. 11/18 (67%) had a previous negative HIV test using laboratory Abbott Ab/Ag tests, 1/18 POCT, in the preceding 12 months to accessing PEP. 18/18 were prescribed NRTI + bPI, 16 of these in line with current UK guidelines. From data available on 16 (2 not diagnosed at our trusts), HIV diagnoses were subsequently made using laboratory Ab/Ag test in 14/16, POCT in 1 and HIV RNA in 1. 1/18 tested negative by POCT and Ab/Ag lab tests at PEP start, subsequently tested HIV+ with a weakly reactive p24 antigen and positive HIV-RNA on laboratory testing 19 days after completing a 28 day PEP course. The remaining 17 patients initiated PEP based on a negative POCT or recent negative HIV antibody test but were subsequently diagnosed HIV+ using lab tests . Therefore 17/18 (94%) of patients were already HIV+ at PEP initiation. Of those diagnosed HIV+ whilst still on PEP, 11/16 (68%) opted to continue ART. A decision was made to stop PEP in 5 patients (mean number of days on PEP; 10); this advice was not influenced by CD4 or HIV RNA. 5/11 switched PEP regimes to first line ART. 2/18 had drug resistance: K103N, T215D at diagnosis. Conclusions: Patients presenting for PEP after sexual exposure are high-risk individuals who may be seroconverting at the time of presentation. It is essential that if a POCT is used at screening, this is accompanied by a 4 th generation test as near to initiation as possible, and that dual therapy (as still recommended in some guidelines) must be avoided in this setting. Acute HIV diagnosis whilst on PEP represents an opportunity for early ART with reduction of viral reservoirs and improvements in CD4 outcome. In the absence of specific data to inform best practice, we recommend continued ART until urgent review by an HIV specialist.

THURSDAY, FEBRUARY 26, 2015 Session P-V2 Poster Session

Poster Hall

2:30 pm– 4:00 pm PrEP and Microbicide Challenge 962 FTC/TDF Prevents SHIV Infection in C trachomatis and T vaginalis -Infected Macaques Jessica Radzio ;Tara Henning; James Mitchell; Angela Holder; Debra Hanson; Janet McNicholl;Walid Heneine; John Papp; Ellen Kersh; Gerardo Garcia-Lerma US Centers for Disease Control and Prevention (CDC), Atlanta, GA, US

Background: Genital tract inflammation associated with pre-existing sexually transmitted infections (STIs) can increase HIV risk and potentially reduce the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a pigtail macaque model of co-infection with Chlamydia trachomatis and Trichomonas vaginalis to investigate if cervicovaginal inflammation due to STIs can decrease the prophylactic efficacy of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Additionally, we evaluated the effect of the STIs on dATP and dCTP concentrations in vaginal tissues. Methods: Eleven female pigtail macaques were inoculated with C trachomatis (serovars D and E) and T vaginalis (strain Balt 42) and exposed vaginally to SHIV once a week for up to 16 weeks. Macaques received placebo (n=5) or FTC/TDF (n=6) 24h before and 2h after each weekly SHIV exposure. C trachomatis and T vaginalis infections were maintained with boosting doses given every 3 to 4 weeks, and were monitored weekly by APTIMA testing. The impact of STIs on dATP and dCTP levels in vaginal tissues was evaluated using biopsy specimens collected from 5 additional macaques 1-3 weeks after STI inoculations. TFV-DP, FTC-TP, dATP, and dCTP levels were measured by HPLC. Results: APTIMA results for C. trachomatis and T. vaginalis were positive in 87% and 81% of vaginal swabs, respectively, demonstrating maintenance of both STIs during the study. All 5 placebo controls were infected with SHIV after a median of 2 (range=2-5) challenges. In contrast, 4 of 6 PrEP-treated animals remained uninfected after 16 challenges ( p <0.01). TFV-DP and FTC-TP levels in PBMCs at the estimated week of infection in the 2 PrEP failures (13 and 31 fmols of TFV-DP and 168 and 188 fmols of FTC-TP per 10 6 cells) were similar to those in the 4 protected macaques (14 to 22 fmols TFV-DP and 160 to 318 fmols FTC/10 6 cells), as were TFV-DP/dATP and FTC-TP/dCTP ratios (p>0.5). C. trachomatis and T. vaginalis infection increased dATP and dCTP levels in vaginal tissues (15 to 32 fmols/mg for dATP, and 3.4 to 9.8 fmols/mg for dCTP; p<0.02). Conclusions: Oral FTC/TDF maintains prophylactic efficacy in a macaque model of prolonged co-STI infection, although the infection of 2 macaques that had protective drug levels signals a modest loss of PrEP activity due to STIs. Increases in vaginal dATP and dCTP levels post-STI likely reflects increased cellular activation and may potentially modulate the efficacy of PrEP by increasing competition with tenofovir and FTC. 963 Impact of Sexually Transmitted Infections on the Efficacy of Tenofovir Vaginal Gel in Macaques Natalia Makarova;Tara Henning; AndrewTaylor; Chuong Dinh; Carol Farshy; Janet McNicholl; John Papp;Walid Heneine; Ellen Kersh; Charles W. Dobard US Centers for Disease Control and Prevention, Atlanta, GA, US Background: Sexually transmitted infections (STI) increase risk of HIV acquisition in women and can potentially diminish efficacy of PrEP, particularly for vaginal gels that rely mainly on local protection of the vaginal mucosa. Here, we used a macaque model of STIs to evaluate if the protective efficacy of vaginal TFV gel is reduced in the presence of STIs. In this model, pigtail macaques co-infected with Chlamydia trachomatis ( CT ) and Trichomonas vaginalis ( TV ) show increased susceptibility to SHIV infection and reproduce the cervicovaginal inflammation documented in women. We additionally assessed the impact of the STIs on vaginal drug absorption. Methods: Female pigtail macaques (n=10) were inoculated vaginally with CT (serovars D and E) and TV (strain Balt 42) and exposed twice-weekly to SHIV162p3 (50 TCID) for up to 10 weeks. STI infections were sustained with boost inoculations given every 3 weeks and were monitored weekly by APTIMA testing. Macaques received placebo (n=4) or 1% TFV gel (n=6) 30 minutes before each SHIV exposure. SHIV infection was monitored by serology and plasma virus load by RT-PCR. Vaginal absorption of TFV from gels was evaluated longitudinally by measuring TFV in plasma by HPLC MS/MS. Results: APTIMA results for CT and TV were positive in 78% and 86% of all vaginal swabs collected, respectively, demonstrating that the dual infections were maintained during the challenge study. All macaques receiving placebo gel were SHIV-infected after a median of 4 weeks (7 challenges). In contrast, all 6 TFV gel-treated animals remained uninfected after 10 weeks (20 challenges), demonstrating that TFV gel maintained complete protection in the presence of STIs. The Tmax for peak TFV levels in plasma after vaginal gel dosing was 30 min. Longitudinal assessment of plasma drug levels revealed peak TFV absorption at Tmax was significantly higher in macaques with STIs compared to non-STI animals (median = 76.64 ± 10.70 and 29.10 ± 3.198 ng/ml, respectively; p<0.0001). Conclusions: In this model, vaginal TFV gel maintained complete protection against SHIV infection in the setting of STI co-infection. The trend for higher TFV concentrations in plasma of STI co-infected than in non-STI animals may reflect higher tissue permeability and drug loading. Both the modest increase in susceptibility by STIs and the high mucosal drug exposures following vaginal gel dosing, likely explain the observed protection by TFV gel.

Poster Abstracts

572

CROI 2015