CROI 2016 Abstract eBook

Abstract Listing

Oral Abstracts

169aLBHIV-1 InfectionWith Multiclass Resistance Despite Preexposure Prophylaxis (PrEP) David C. Knox 1 ; Darrell H.Tan 2 ; P. Richard Harrigan 3 ; Peter L. Anderson 4

1 Maple Leaf Med Clinic, Toronto, ON, Canada; 2 St Michael’s Hosp, Toronto, ON, Canada; 3 BC Cntr for Excellence in HIV/AIDS, Vancouver, BC, Canada; 4 Univ of Colorado, Denver, CO, USA Background: PrEP is reported to have nearly 100% prevention efficacy in men who have sex with men (MSM) when adherence is high. We report a 43 year old MSM who seroconverted to multi-class resistant HIV-1 (day 0; 4th generation Ag/Ab combo screen positive, p24 positive, Western Blot negative) after 24 months of successful PrEP, despite clinical and pharmacokinetic data suggesting long-term adherence to FTC/TDF. Methods: Pharmacy dispensing records were obtained for FTC/TDF. Liquid chromatography–mass spectrometry (LC-MS) was performed on the untimed plasma sample from day 0 to determine TDF and FTC concentrations. Dried blood spots (DBS) were collected on day 16, while on FTC/TDF-based combination antiretroviral therapy, for determination of intracellular TVF-DP concentration. Standard population sequencing and deep sequencing to 2% of the viral population was completed on day 7 plasma (HIV RNA 28,326 copies/ mL), as was phenotypic testing for resistance to integrase inhibitors. Phylogenetic analysis of the V3 loop of envelope protein gp120 was completed on day 7 plasma to characterize the founder virus. Results: Pharmacy dispensing records demonstrated consistent prescription refills. DBS testing revealed TVF-DP of 2,297 fmol/punch indicating consistent dose-taking in the preceding 1-2 months, thus overlapping with the seroconversion time. LC-MS on day 0 plasma was inconclusive for TDF (calibration range 181-2,385 ng/ml) and FTC (range 736- 50,200 ng/ml) due to the untimed nature of the sample relative to dosing and the high lower limit of quantification of the assay. Standard and deep sequencing of virus from day 7 revealed CCR5-tropic clade B HIV-1 with mutations conferring resistance to NRTIs (41L, 67G, 69D, 70R, 184V, 215E), NNRTIs (181C) and INSTIs (51Y, 92Q), suggesting transmitted rather than acquired resistance (table 1). Phenotypic drug resistance testing of the integrase class on day 7 plasma revealed reduced response to all integrase inhibitors (table 1). Phylogenetic analysis revealed a very narrow range of sequence diversity, consistent with infection from a single source. Conclusions: This patient’s clinical history, pharmacy records and DBS results consistent with long-term dosing of FTC/TDF suggest that HIV infection is possible despite adherence to daily oral PrEP when exposed to FTC/TDF-resistant virus. To our knowledge, this is the first reported case of breakthrough HIV infection with evidence of long-term adherence to FTC/TDF.

169bLB Gel Applied as Anal LubeWithout Applicator Provides Poor Rectal Mucosal HIV Coverage Eugenie Shieh 1 ; EthelWeld 1 ; Edward J. Fuchs 1 ; KarenW. Buckheit 2 ; RobertW. Buckheit Jr 2 ; Jennifer Breakey 1 ; Craig Hendrix 1 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 ImQuest Biosciences, Frederick, MD, USA

Oral Abstracts

Background: With the rising incidence of HIV in men who have sex with men (MSM) and the proven efficacy of oral HIV pre-exposure prophylaxis, more behaviorally-congruent periodic dosing strategies, such as rectal HIV microbicides, are in demand. Rectal gel microbicide studies have utilized vaginal applicators to administer the gels, but these applicators have not been well received. Further, this doesn’t mimic the real-world use of sexual lubricants, which usually involves application inside or on the anus and on the partner’s penis. We examined the rectal distribution of gels when dosed as sexual lubricants compared to dosing with an applicator. Methods: Five healthy, HIV-negative MSM were enrolled. 10 mL of 99mTc-DTPA-radiolabelled hydroxyethyl cellulose (HEC) gel universal placebo was administered intra- rectally with a 4 cm applicator attached to a syringe. After washout, the same participants were given 10 mL of 99mTc-DTPA-radiolabelled Wet® Original gel lubricant for self- administration to the anus with use of fingers and a phallic device as if applying a sexual lubricant in their usual manner with a sexual partner (manual dosing). Manual dosing was then followed by 5 minutes of simulated receptive anal intercourse with a phallic device. SPECT/CT was performed 4 hours after each gel administration. Results: Gel administered by both methods was centered in the rectosigmoid, median 7.7 cm (interquartile range 5.2-13.4) from the anorectal junction. However, the manual dosing method was associated with more variable distribution, 12.5 cm (7.3-37.0), compared to a more uniform 18.1 cm (17.35-18.5) distribution after applicator dosing. When applying the gel manually as a sexual lubricant, participants utilized 2.7 mL (1.8, 6.6) of the 10 mL lubricant dose unit. Of the initial 10 mL dose intended for manual application, only 4% (1%, 27%) was retained within the colon after simulated sex. By contrast, 92% (91%, 93%) of the applicator dose was retained (paired t-test, p=0.01). Conclusions: Manual application of a sexual lubricant gel delivers a small, variable fraction of the gel dose in a variable rectosigmoid distribution compared to the same volume dosed intra-rectally. These preliminary results raise concern that manually dosing a rectal microbicide gel as a sexual lubricant may not provide adequate, predictable mucosal coverage for HIV protection. Assessment of antiretroviral rectal microbicide products is needed to confirm these preliminary results.

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CROI 2016