CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

956 Virologic Failure Is Uncommon After Treatment Is Initiated During Acute HIV Infection Trevor A. Crowell 1 ; Nittaya Phanuphak 2 ; Suteeraporn Pinyakorn 1 ; Donn Colby 2 ; SompornTipsuk 2 ; Putthachard Kansomlap 2 ; Naphassanant Laopraynak 3 ; Robert O’Connell 4 ; Merlin L. Robb 1 ; Jintanat Ananworanich 5 ; for the RV254/SEARCH010 Study Group 1 US Military HIV Rsr Prog, Walter Reed Army Inst of Rsr, Silver Spring, MD, USA; 2 SEARCH, Bangkok, Thailand; 3 HIV-NAT, Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand; 4 Armed Forces Rsr Inst of Med Scis, Bangkok, Thailand; 5 Military HIV Rsr Prog, Bethesda, MD, USA Background: When initiated during chronic HIV infection, antiretroviral therapy (ART) generally produces a swift decrease in viral load (VL) and suppression within 24 weeks. We investigated viral dynamics and common criteria for treatment success after ART initiation during acute HIV infection (AHI). Methods: Subjects were prospectively enrolled and offered ART during AHI fromMay 2009-February 2015 in Bangkok, Thailand. Regimens included tenofovir, lamivudine, and efavirenz with or without raltegravir and maraviroc. Subjects were monitored for the following VL endpoints: (1) 1-log reduction by week 2; (2) 2-log reduction by week 4; (3) <1000 copies/mL by week 24; and (4) <200 copies/mL by week 24. Associated factors were explored using the chi-squared test and t-test. The log-rank test was used to evaluate associations with time to VL <200 copies/mL. Results: From 130,704 samples screened for HIV, 237 Thai subjects were enrolled and initiated ART during AHI. Their median age was 27 years and 95%were male. ART was initiated during Fiebig I in 15%, Fiebig II 29%, Fiebig III 40%, Fiebig IV 11%, and Fiebig V 5%. ART included raltegravir and maraviroc for 84 subjects (35%) and regimens did not differ by Fiebig stage (p=0.382). Only 16 of 236 (6.8%) subjects with VL data at week 2 did not achieve a 1-log reduction in VL. At 4 weeks, 25 of 234 (10.1%) had not achieved a 2-log reduction in viral load. At 24 weeks, 3 of 230 (1.3%) had not reached VL <1000 copies/mL and 4 (1.7%) had not reached VL <200 copies/mL. Subjects treated during Fiebig I had lower VL at ART initiation (mean [SD] 4.31 [0.69] log 10 copies/mL vs. 6.0 [0.88] in all other subjects, p<0.0001) and were the least likely to achieve early reductions in VL (Figure). At baseline, nine (25%) had VL <5000 copies/mL and none had VL <500 copies/mL. All subjects who initiated ART during Fiebig I achieved VL <200 by week 24 and the median time to viral suppression in this group was only 4 (IQR 2-8) weeks compared to a median 8 (IQR 4-12) weeks for all other Fiebig stages (p=0.002). Subjects who received raltegravir and maraviroc had a median time to suppression of 4 (IQR 4-8) weeks compared to a median 8 (IQR 8-12) in subjects who did not (p<0.0001). Conclusions: Subjects who begin ART during Fiebig I have a low VL and do not demonstrate the same magnitude of early VL decline as is seen when ART is started later. Treatment success can be readily assessed after 24 weeks of ART initiated during AHI. Virologic failure was uncommon in this cohort.

Poster Abstracts

957 A Meta-Analysis Estimating Early Mortality ART in HIV-Positive Adults on ART in LMIC Alana Brennan 1 ; Lawrence Long 2 ; Johanna C. Useem 3 ; Lindsay Garrison 3 ; Matthew P. Fox 1 1 Boston Univ, Boston, MA, USA; 2 Univ of the Witwatersrand, Wits Hlth Consortium, Johannesburg, South Africa; 3 Boston Univ Sch of PH, Boston, MA, USA

Background: While scale-up of ART in low- to middle-income countries (LMIC) has decreased mortality amongst HIV patients, it is unclear whether changes in ART guidelines to make more people eligible has decreased early mortality on ART. Previous meta-analyses reported mortality estimates of 12-months post-ART initiation; however, 40-60% of deaths occur in the first 3-months on ART, which is a more sensitive measure of averted deaths through early ART initiation than 12 month rates. We systematically reviewed studies of mortality in the first 3-months post-ART initiation in Asia, sub-Saharan Africa (SSA), and the Americas. Methods: Studies of mortality within 3-months post-ART initiation published in English from January 2003-October 2014 were searched in PubMed, Web of Science, EMBASE and conference abstracts (IAS and AIDS). Articles were included if they were conducted in a LMIC; in a non-trial setting; participants were >15 and reported 3-month mortality. Using random effects models (high heterogeneity between studies) we assessed 3-month mortality overall and stratified by region, CD4 count at ART initiation and time. Results: 54 studies were included; 43 (78%) from SSA, 10 (19%) from Asia, 1 (2%) from the Americas. Overall 3-month mortality was 5.9% (95%CI:5.1-6.8%). Mortality for SSA, the Americas and Asia was 5.9% (95%CI:5.0-7.0%), 7.1% (95%CI:6.1-8.1%) and 5.4% (95%CI:4.0-7.1%), respectively(Figure). Studies with a median CD4 >200cells/mm 3 at ART initiation had lower mortality (4.4%; 95%CI:3.3-5.6%) vs. studies reporting a median of 100-200cells/mm 3 (6.2%; 95%CI:5.0-7.5%) and <100cells/mm 3 (8.4%; 95%CI:7.5-10.5%). The overall pooled estimate shows no difference in mortality when comparing studies whose enrollment of patients ended <2010 (5.7%; 95%CI:4.7-6.8%) to >2010 (6.2%; 95%CI:4.8-7.8). Conclusions: Excluding the Americas, as summary estimates were based on one study, our results showed mortality in the first 3-months on ART were comparable in SSA and Asia. As expected, patients with low CD4 count at ART initiation were at higher risk of death. Our results showed no difference in early mortality over time, potentially due to lack of follow-up time in studies to evaluate the impact after the effect of the 2010 WHO guideline changes. As LMIC increase access to care, raise the CD4 eligibility threshold to 500 cells/ mm 3 or move towards a test-and-treat model of care, the expectation is mortality in the first 3 months on ART will begin to decline.

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CROI 2016