CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Methods: 250 HIV+, ART-naive adults were randomized to either open-label zidovudine-lamivudine-nevirapine (ZLN) or tenofovir-lamivudine-efavirenz (TLE) at two hospitals in Beijing. All subjects were NC normal and had CD4+ T-cell counts below 350/mm 3 at entry. Subjects were followed for 96 weeks with comprehensive NC testing and safety assessments. NC performance was adjusted for local normative data and summarized by the Global Deficit Score (GDS) and by the proportion of subjects who developed incident NCI. NC change was summarized using a regression-based summary change score (SCS). Intent-to-treat completer (ITT-C, n=239) and as-treated (AT, n=189) analyses were performed. Results: The treatment groups had similar demographic and disease characteristics, including plasma HIV RNA (mean 4.2 log 10 copies(c)/mL in both groups) and CD4+ T-cell counts (mean 235.1 (ZLN) vs. 222.1 (TLE), p=0.32). GDS values at entry were also similar (mean 0.12 (ZLN) vs. 0.14 (TLE), p=0.15). A high proportion of subjects attained virologic suppression: 92% had plasma HIV RNA below 50 c/mL in both groups at 48 weeks (p=.65, ITT-C). TLE was associated with greater risk of incident NCI over 96 weeks than ZLN in either ITT-C (p=.009) or AT (p=0.037) analyses. Consistent with this finding, the SCS also differed between the groups at 96 weeks (ITT-C: d=.27, p=0.016; AT: d=.28, p=0.034). Safety assessments identified that 73/128 (57.0%) subjects in the ZLN group had at least one adverse event compared with 42/122 (34.4%) in the TLE group, leading to greater discontinuation of study drugs in the ZLN group (38% vs. 2%, p<.001). The most common adverse events were liver toxicity and bone marrow suppression. Conclusions: This is the first randomized clinical trial to demonstrate that ART regimens differ in preventing NC decline using comprehensive NC testing. Possible explanations include differences between the regimens in drug distribution into the CNS and neurotoxicity. The substantial difference in other adverse events dictates additional research to identify a less toxic alternative to ZLN. 57 Neurocognitive Function in Africans Failing First-Line ART and Responses to Second Line Andrew D. Kambugu 1 ; JenniferThompson 2 ; James Hakim 6 ; DinahTumukunde 10 ; Joep van Oosterhout 7 ; Anne Hoppe 2 ; Charles Kwobah 9 ; SarahWalker 2 ; Nicholas Paton 8 On behalf of the EARNESTTrialTeam 1 Infectious Diseases Institute, Makerere University Kampala, Kampala, Uganda; 2 University College London, London, United Kingdom; 3 Joint Clinical research Centre, Kampala, Uganda; 4 Queen Elizabeth Central Hospital, Malawi, Blantyre, Malawi; 5 AMPATH, Kenya, Eldoret, Kenya; 6 University of Zimbabwe, Harare, Zimbabwe; 7 Dignitas International, Zomba, Malawi; 8 National University of Singapore, Singapore, Singapore; 9 Moi University College of Health Sciences, Eldoret, Kenya; 10 Joint Clinical Research Centre, Kampala, Uganda Background: Neurocognitive impairment is an important co-morbidity in HIV infection. Data describing neurocognitive function in patients from sub-Saharan Africa are generally sparse, with only limited data describing neurocognitive function at the time of failure of first-line therapy, and none describing the changes in neurocognitive function in response to second-line therapy. Methods: We studied patients who were enrolled in EARNEST, a large multi-centre trial of second-line therapy conducted at 14 sites in sub-Saharan Africa. Eligible patients were >12 years old and failing first-line therapy according to WHO criteria after >12 months on an NNRTI-based regimen. Patients were randomised to take second-line therapy (open-label) with lopinavir/ritonavir (400mg/100mg twice daily) plus either 2-3 clinician-selected NRTIs, raltegravir, or as monotherapy after 12 weeks’ induction with raltegravir. Neurocognitive function was tested on those aged >18 years at baseline (switch to second-line), weeks 48 and 96 using colour trails tests 1 and 2, and the grooved pegboard test. Test results were converted to a composite z-score using US test norms. Results: 1036 patients (>86% of those >18 y enrolled in the trial) had evaluable tests at baseline, and 915 patients at week 96. Patients were 58% female, mean age 38 years, median viral load 65,000 c/ml, median CD4 count 73 cells/mm3 at first-line failure. Mean (SD) composite z-score at baseline was -2.96 ± 1.74; z-scores were independently lower in older individuals, and those with lower body weight, higher viral load, lower haemoglobin, fewer years of education, fewer working hours per week, previous CNS disease, or taking fluconazole (all P<0.05 in a multivariable model). Neurocognitive function improved markedly after starting second-line therapy (mean (SE) increase in Z-score of +1.23 (0.04) at week 96), with no difference between the arms (P=0.35; Figure 1).

Oral Abstracts

Figure 1: Changes in z-score over 96 weeks in the three randomised groups Conclusions: Patients in sub-Saharan Africa failing first-line therapy appear to have severely impaired neurocognitive function. In part this may reflect inadequate data for normalization, but the relationship with high viral load and indicators of general debility suggest much of the impairment is HIV-related. Neurocognitive function improves markedly on second-line therapy. The lack of difference between standardised treatment regimens with very different CNS penetration indicates that this need not be a primary consideration in the choice of an optimal drug regimen for second-line therapy. 58 Compartmentalized HIV Rebound in the CNS After ART Interruption Sara GianellaWeibel ; Michelli Faria de Oliveira; Konrad Scheffler; Matt Strain; Antonio De laTorre; Scott Letendre; David M. Smith; Sergei L. Kosakovsky Pond; Ronald J. Ellis University of California San Diego, La Jolla, CA, US Background: If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments, including the central nervous system (CNS). To design effective eradication strategies, it is crucial to determine to what extent compartmentalized HIV reservoirs contribute to viral rebound after antiretroviral therapy (ART) interruption Methods: Paired blood and cerebrospinal fluid (CSF) samples were collected from 14 chronically HIV-infected individuals undergoing ART interruption. At the first two available time-points following viral rebound, we sequenced HIV-1 env ( C2-V3 ), gag (p24), and pol ( reverse transcriptase) regions amplified from cell-free HIV RNA in blood and CSF using

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CROI 2015