CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: 100 men (mean age 31 years [SD 9]) presented a mean 30 hours (SD 21) after anal sex (88% receptive). NPEP commenced 2 hours (SD 2.3) post-presentation. No participant was HIV+ at enrolment or through Week 12, or ceased NPEP because their ‘source’ was found to be HIV-negative. NPEP completion was 92% (95%CI 85 to 96); failures occurred at median 14 days for loss to follow-up (6%), adverse event (1%) or study burden (1%). NPEP adherence was 98.6% (SD 2.7) by self-report. In the 78 participants with pill-count data, adherence was 98.7% (SD 2.4). 86% reported taking all doses with food. Of 78 paired assessments available for percent adherence by pill count and self-report, agreement was 100% (kappa=1.0; P<0.0001). From the final 50 participants, plasma TFV was measured within 48 hours of the last dose in 41 (88%) participants who reached Day 28 (mean 16 hrs [SD 10]): 36 (88%) participants had levels >40ng/mL and only 1 (2%) was <10ng/mL. One participant developed pancreatitis 1 day post-NPEP. 5 other participants developed a Grade 3 AE; 2 possibly due to study drug . Grade 3+ lab AEs possibly due to study drug occurred in 2 participants. Mean serum creatinine rose from 83 to 88 m M/L at Day 28 (P<0.001), but with no grade 1+ increase and no significant change in serum phosphate. Conclusions: STR FTC/RPV/TDF was well-tolerated as once-daily NPEP, with high levels of adherence and completion. 959 Tenofovir/Emtricitabine Plus LPV/r vs MVC or Raltegravir for PEP: 2 Randomized Trials Lorna Leal ; Agathe Leon; BertaTorres; Alexy Inciarte; Constanza Lucero; Josep Mallolas; Maria Martinez-Rebollar; Ana González-Cordón; Jose M. Gatell; Felipe Garcia Hospital Clínic Barcelona, Barcelona, Spain Background: PEP is recommended after a potential exposure to HIV. In animal models, PEP has to be maintained 4 weeks to be effective. However, with the recommended regimens in humans, side effects are frequent and are the main reason for poor adherence and a high rate of discontinuation. The objective of these 2 trials was to assess the rate of discontinuation of PEP at 28 days comparing the standard of care Lopinavir/r (LPV/r) vs Maraviroc (MVC) or Raltegravir (RAL) both with Tenofovir/Emtricitabine ( TVD). Methods: Individuals coming to the emergency room (ER) for potential sexual exposure to HIV were randomized to: TVD 200/245 QD plus LPV/r 400/100 BID (n=117) or plus MVC 300 BID (n=120) in one trial (n=237) and TVD plus LPV/r (n=121) or plus RAL 400 BID (n=122) in the second trial (n=243). After randomization, 4 follow-up visits were scheduled: day 0, 28, 90 and 180. The primary end-point was rate of discontinuation at day 28. Secondary end-points were adherence to PEP, side effects and rate of seroconversions. Results: In MVC and RAL trials, median age was 35 and 33 years and 92% and 90%were males respectively. The median interval between exposure and presentation at ER was 15h and 13.5h. Type of exposition was male homosexual sex in 83% and 81%. The level of risk was high in only 13% and 9% of individuals. The source patient was known to be HIV infected in 30.8% and 31%. In MVC trial, only 187/237 (79%) who were randomized and started PEP attended the first scheduled visit (day 0) and differences between arms were not observed (p=0.92). Similar results were found in RAL trial [198/243 (81.5%) attended the day 0 (p=0.62)]. The rate of discontinuation of PEP before day 28 of follow-up was significantly higher in LPV/r (31.5%) vs MVC (11.6%) arm (p=0.001) and in LPV/r (36.6%) vs RAL (23.7%) arm (p=0.04). The proportion of patients with low adherence to PEP was similar in LPV/r vs MVC arms (54% vs 46%, respectively, p=0.56), but was higher in LPV/r vs RAL arms (49.2% vs 30.8%, respectively, p=0.03). Adverse effects were reported in 122 out of 187 (50.8%) patients in MVC study attending at least the day 0 visit [70/92 (76.1%) in LPV/r and 52/95 (54.7%) in MVC arm, p=0.002] and in in 134 out of 198 (67.7%) patients in RAL study [75/101 (74.3%) in LPV/r and 59/97 (60.8%) in RAL arm, p=0.04]. No seroconversions were observed. Conclusions: The rate of discontinuation of PEP and side effects were higher in patients allocated to TVD plus LPV/r as compared with those with TVD plus MVC or TVD plus RAL. 960 Effects of Three Regimens of PEP on the Immune System of HIV-Seronegative Individuals Alberto C. Guardo 1 ; Lorna Leal 2 ; Agathe Leon 2 ; Cristina Rodriguez de Miguel 2 ; Manel E. Bargallo 1 ; Cristina Rovira 1 ; Josep Llach 2 ; Jose M. Gatell 2 ; Felipe Garcia 2 ; Montserrat Plana 1 1 L’Institut D’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; 2 Hospital Clinic, Barcelona, Spain Background: According to studies in animal models, Postexposure Prophylaxis (PEP) has to be maintained 4 weeks to be effective. However, with the diversity of the actual regimens, the consequences of those temporary window treatments at immunological level are not well characterized. The objective of this pilot study was to assess the immunological effects of antiretroviral therapy during 28 days of PEP comparing the standard of care Lopinavir/r (LPV/r) vs Maraviroc (MVC) or vs Raltegravir (RAL), all of themwith Tenofovir/Emtricitabine (TVD). Methods: Peripheral blood mononuclear cells (PBMCs) and mononuclear cells (MNC) from rectal biopsy specimens were collected from 30 men who have sex with men (MSM) with a potential sexual exposure. All of themwere selected from two different PEP randomized clinical trials. Three arms (TVD plus LPV/r (n=9) or plus MVC (n=11) or plus RAL (n=10)) and four follow-up visits were scheduled (day 1, 7, 28 and basal). Flow cytometry was used to measure immune activation (CD38 and HLA-DR), senescence (CD57 and CD28) and CCR5 expression in CD4 and CD8 T cells. Additionally levels of naïve, effector and memory T cells (CCR7 and CD45RA) were also evaluated. Results: In PBMCs senescence and activation of CD4 T cells improved significantly in RAL arm between basal and day 28 (CD28: 93.5% vs 97.5%, p= 0.02; CD57: 4.8% vs 1.5%, p=0.03; CD38+DR+: 5.8% vs 2.6%, p=0.05, respectively) whereas no changes were observed in the other two regimens. At the same time points MVC arm, increased significantly the expression of CCR5 in both lineages CD4 (4.7% vs 15%, p=0.002) and CD8 (6.3% vs 16.1%, p=0.004) T cells, probably as a consequence of blockade of its internalization. No differences were detected at basal time among arms and only at day 28 was observed that RAL arm reduced significantly the mentioned percentage of CD4+CD38+DR+ in comparison with MVC arm (7.4% vs 2.6%, p=0.02, respectively). Regarding rectal biopsies not significant differences were detected among arms except for a marked increase in the proportion of CD4 naïve T cells in MVC arm (RA+CCR7+:35.8% vs 46%, p=0.03). Conclusions: The rates of activation and senescence of the immune systemwere significantly lower in CD4 T cells from individuals on PEP with TVD plus RAL as compared with those with the other two regimens. Although these data should be confirmed due the low number of patients, our findings in combination with the results of better adherence and tolerance strongly support RAL regimens for PEP. 961 Management of Acute HIV After Initiation of Postexposure Prophylaxis: Challenges and Lessons Learnt Goli Haidari 1 ; Naomi Fitzgerald 4 ; Sonia Raffe 2 ; Nneka Nwokolo 3 ; Olamide Dosekun 1 ; Mark D. Lawton 5 ; Nickie Mackie 1 ; Julie Fox 4 ; Martin Fisher 2 ; Sarah Fidler 1 1 St Mary’s Hospital–Imperial College Healthcare NHS Trust, London, United Kingdom; 2 Brighton and Sussex Hospitals NHS Trust, Brighton, United Kingdom; 3 Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom; 4 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 5 The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom; 6 St Mary’s Hospital–Imperial College Healthcare NHS Trust, London, United Kingdom; 7 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 8 Brighton and Sussex Hospitals NHS Trust, Brighton, United Kingdom; 9 St Mary’s Hospital–Imperial College Healthcare NHS Trust, London, United Kingdom Background: International guidelines recommend HIV post exposure prophylaxis following sexual exposure (PEPSE) to prevent HIV infection. However, methods to screen for infection prior to initiating PEPSE are less clear, with little or no guidance for management of acute HIV diagnosed during PEPSE. We present a case series of individuals diagnosed HIV+ whilst on PEPSE. Methods: Cases definitions include the following criteria: 1. PEPSE failure: negative point of care test (POCT) and 4 th generation laboratory test at PEP start, with HIV diagnosed during PEP or in follow up period 2. Acute HIV infection at PEPSE initiation: negative POCT but subsequent reactive 4 th generation test at PEP start

Poster Abstracts

571

CROI 2015