CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

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. 957 Significant Intolerability of Efavirenz in HIV Occupational Postexposure Prophylaxis SurasakWiboonchutikul 1 ;VarapornThientong 1 ; Patama Sutha 1 ; Boonchai Kowadisaiburana 2 ;Weerawat Manosuthi 1 1 Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand; 2 Bangkok Hospital, Bangkok, Thailand Background: Postexposure prophylaxis (PEP) has been used to decrease a risk of HIV transmission after occupational exposure. Regimen completion is one of the most important factors in successful prophylaxis. Limited data are available on tolerability of PEP regimens in healthcare workers (HCWs) in resource-limited settings. We aimed to describe the characteristics of occupational exposure, and sought to determine factors associated with incompletion of the 4-week HIV prophylactic course. Methods: A retrospective study was conducted among HCWs who accidentally exposed to blood or body fluid of patients at Bamrasnaradura Infectious Diseases Institute, Thailand, between March 1996 and June 2014. The characteristics of exposure were described, and logistic regression analysis was used to determine factors associated with incompletion of the 4-week prophylactic course. Results: A total of 225 exposure episodes were reported (163 percutaneous injury, 43 mucosal exposure, 6 non-intact skin exposure, and 13 intact skin exposure). The mean (SD) age was 33.1 (9.9) years and 189 (84%) were females. The most frequently exposed groups were nurses (43%), patient or nurse assistants (18%), and medical technicians (15%). The HIV status of the source was defined in 149 (66%) episodes which were positive in 101 (68%). Of 225 exposures, PEP was prescribed in 155 (69%) episodes but was subsequently intentionally discontinued in 26 episodes (HIV source was negative in 19, refusal to continue in 7). PEP courses should have completed in 129 episodes. Of 129 prescribed regimens, 38%were 2 NRTIs, 37%were 2 NRTIs + PIs, 12%were Zidovudine alone, 9%were 2 NRTIs + Efavirenz (EFV), and 4%were 2 NRTIs + Raltegravir. Only 91 of 129 (71%) HCWs were able to complete the 4-week regimen. Multivariate analysis showed that 2 NRTIs + EFV was the only significant factor associated with incompletion of the 4 week-course (OR 33.3; 95% CI 4.2-100; p < 0.01). Other factors including age, gender, staff position, status of the source, and other PEP regimens were not associated with incompletion of the 4-week course ( p > 0.05). The reason for premature discontinuation of 2 NRTIs + EFV was intolerability in all HCWs. None of the HCWs was reported to have HIV seroconversion. Conclusions: Two NRTIs + EFV regimen was significantly associated with premature discontinuation of occupational PEP. This regimen should not be further used for HIV prophylaxis following occupational exposure in the resource-limited settings. 961 Management of Acute HIV After Initiation of Postexposure Prophylaxis: Challenges and Lessons Learned 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 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.

Oral Abstracts

Session S-7 Symposium

Room 613

4:00 pm– 6:00 pm From Pathways to Paradigms: Applications of Systems Biology to HIV/Host Interactions 171 Using Systems Approaches to Study Pathogenesis: Bridging Networks and Mechanisms Nevan Krogan University of California San Francisco, San Francisco, CA, US

There is a wide gap between the generation of large-scale biological data sets and more-detailed structural and mechanistic studies. However, recent work that explicitly combine data from systems and structural biological approaches is having a profound effect on our ability to predict howmutations and small molecules affect atomic-level mechanisms, disrupt systems-level networks and ultimately lead to changes in organismal fitness. Our group aims to create a stronger bridge between these areas primarily using three types of data: genetic interactions, protein-protein interactions and post-translational modifications. Protein structural information helps to prioritize and functionally understand these

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CROI 2015