CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: HAART was initiated in naïve patients according to the national guidelines; HIV-1/O and HIV-1/M patients were matched on sex, age, CD4, Hb level and HBV status with ratio of 1:2. The primary endpoint was the percentage of patients having an undetectable viral load (VL < 60 cp/mL) at W96. Adherence to treatment was also monitored. Results: 47 Cameroonian patients HIV-1/O and 94 HIV-1/Mwere included; results were available for 128 patients (13 died or were lost-to follow-up). At baseline, VL was significantly lower (p< 0.0001) in HIV-1/O with a median at 4.3 log cp/mL versus 5.1 in HIV-1/M. Kinetic of VL response was faster for HIV-1/O infected patients until W24. At W96, 95% of HIV-1/O samples were < 60 cp/mL vs 83% of HIV-1/M in per protocol analysis (p=0.09); but no difference was observed at the threshold of 200 cp/mL (97% in both groups). At baseline, median CD4 counts were well balanced between the two groups (227 vs 215, in HIV-1/O and HIV-1/M respectively, p=0.68); at W96, a +50% CD4 gain compared to baseline was observed for 78% vs 89% of the HIV-1/O and HIV-1/M patients respectively (p=0.27), confirming the differences observed at W24 and W48. Adherence monitoring at W24, W48, and W96 revealed no impact on the differences observed between the two groups. Conclusions: DynaM-O is the unique study analyzing the HAART responses in HIV-1/O infected patients compared to HIV-1/M patients. Data at W96 showed good efficacy of the regimens in both groups, but with a higher rate of achievement of the virological response in HIV-1/O infected patients. In contrast, the CD4 restoration was lower in HIV-1/O than that observed for HIV-1/M patients. These data indicate that group O infected patients should be successfully treated by treatment excluding NNRTI. Moreover, studying the mechanisms underlying these differences in response to HAART between these highly divergent HIV-1 strains are of importance in our understanding of the HIV natural history. 960 Clinical Outcomes With Tenofovir Use in ART: Regression Discontinuity Analysis Alana Brennan 1 ; Matthew P. Fox 1 ; Mary-Ann Davies 2 ; Kathryn Stinson 3 ; RobinWood 4 ; ProzeskyW. Hans 5 ; FrankTanser 6 ; Geoffrey Fatti 7 ;Till Bärnighausen 8 ; GillesWandeler 9 ; Andrew Boulle 2 ; Izukanji Sikazwe 10 ; Jacob Bor 11 ; Arianna Zanolini 10 1 Boston Univ, Boston, MA, USA; 2 Cntr for Infectious Disease Epi and Rsr, Cape Town, South Africa; 3 Cntr for Infectious Disease Epi and Rsr, Cape Town, South Africa; 4 Univ of Cape Town, Cape Town, South Africa; 5 Univ of Stellenbosch & Tygerberg, Stellenbosch, South Africa; 6 Africa Cntr for Hlth and Pop Studies, Mtubatuba, South Africa; 7 Kheth’Impilo AIDS Free Living, Cape Town, South Africa; 8 Harvard Sch of PH, Boston, MA, USA; 9 Univ Hosp Bern, Bern, Switzerland; 10 Cntr for Infectious Disease Rsr in Zambia, Lusaka, Zambia; 11 Boston Univ Sch of PH, Boston, MA, USA Background: Most countries now recommend initiating HIV patients on tenofovir (TDF) as the standard NRTI in first-line therapy to reduce toxicities associated with the NRTI stavudine. Exploiting national guideline changes in South Africa (SA) and Zambia, we assessed the causal impact of a policy to initiate TDF on ART outcomes using regression discontinuity. Methods: Prospective cohort study of ART-naïve, non-pregnant, HIV patients >16 years who initiated first-line ART in SA or Zambia (IeDEA-SA). Patients initiating ART +/-12 months around the national guideline changes were included: SA-1 April 2010 and Zambia-1 July 2007. We implemented a regression discontinuity, a quasi-experimental design, using the timing of national guideline changes as natural experiments. Patients initiating just before/after guideline change are similar but receive different regimens. Comparing those patients, we estimated the intent to treat (ITT) effect of guideline change on single-drug substitution (SDS), death, loss to follow-up (LTFU), CD4 response and virologic failure (VF, SA only) in the first 24-months on ART on a risk difference (RD) scale using local linear regression. We excluded patients initiating +/-14 days of the date of the guideline change in all estimates due to imprecision in the implementation of the guidelines. We then collapsed across country to estimate combined ITT effects. Results: 16,773 South African and 44,399 Zambian patients were eligible. The probability of initiating TDF increased in both countries for patients starting ART after the guideline changes(Figures A and B). ITT estimates showed a significant decrease in the risk of SDS in SA(RD:-14%; 95%CI:-18%,-11%)(Figure C), while we saw no difference in Zambia(Figure D). In both countries we saw no effect on mortality(SA RD:1.0%; 95%CI:-2.2,4.0%; Zambia RD:-0.3%; 95%CI:-2.2,1.5%), LTFU(SA –RD:2.6%; 95%CI:-6.8,1.5%; Zambia RD:-1.0%; 95%CI:-3.4,1.3%), mean CD4(SA RD:10.1; 95%CI:-43.5,23.2; Zambia RD:5.9; 95%CI:-9.1,20.9), or VF in SA(RD:0.0%; 95%CI:-2.1,41.9%). Combined ITT estimates showed a significant increase in TDF (RD:37%; 95%CI:25%,48%) and no difference in outcomes. Conclusions: Guideline changes led to an impressive increase in tenofovir initiation in SA and Zambia. Initiating patients on TDF led to reductions in SDS in SA, suggesting that a global policy to initiate TDF may have resulted in fewer patient-years spent on sub-optimal therapy and fewer patients experiencing side effects/toxicities. No change was observed in other outcomes.

Poster Abstracts

961 24-Week Results of Elvitegravir-Cobicistat-Emtricitabine-Tenofovir DF for HIV-2 Selly Ba 1 ; Dana N. Raugi 2 ; Robert A. Smith 2 ; Fatima Sall 1 ; Khadim Faye 1 ; Stephen E. Hawes 2 ; Salif Sow 1 ; Moussa Seydi 3 ; Geoffrey S. Gottlieb 2 ; for the University ofWashington–Dakar HIV-2 Study Group 1 Clinique des Maladies Infectieuses, Dakar, Senegal; 2 Univ of Washington, Seattle, WA, USA; 3 CHU de Fann, Dakar, Senegal Background: There is an urgent need for safe and effective antiretroviral therapy (ART) for HIV-2 infection. HIV-2 treatment is complicated by intrinsic resistance to many FDA-approved HIV-1 drugs, and multidrug-resistance is common in individuals failing ART. There are limited options for 1 st - and 2 nd -line ART for HIV-2 in resource-limited settings. An increasing body of data suggests that integrase inhibitor-based regimens may be of potential utility for the treatment of HIV-2. We have undertaken the first clinical trial of a once-daily fixed-dose combination pill containing elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (EVG/c-FTC-TDF) to assess the effectiveness of this regimen in HIV-2-infected subjects in Senegal, West Africa. Methods: HIV-2-infected, ART-naïve adults with WHO stage 3 or 4 disease or CD4 counts below 500 cells/ul were eligible for this open-label pilot trial (NCT02180438), with planned enrollment of 30 subjects and follow-up for 48 weeks. Enrolled subjects are monitored every four weeks for clinical and immuno-virologic outcomes as well as adverse events. For this 24-week interim analysis, changes in plasma viral load, CD4 counts, adverse events, all-cause mortality and loss to follow-up were analyzed.

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CROI 2016