CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

NRTI + ATV/r or LPV/r) and the majority were susceptible or had low-level resistant to DRV/r (97%) and ETR (79%). Nadir CD4 count but not screening HIV RNA was significantly associated with the number of resistant drug classes but quantitative differences were small and unlikely to be helpful clinically (Table). Conclusions: Highly divergent resistance profiles were observed among study candidates being evaluated for 3 rd -line ART in RLS. The majority remained susceptible to 2 nd -line regimens (69%) but others had high level resistance to 2 (31%) and 3 drug classes (26%). Routine clinical parameters were not discriminatory for the extent of resistance. These results indicate that objective measures of ART adherence and access to both resistance testing and newer ARVs are needed to guide 3 rd -line ART in RLS.

494LB Prospective Randomized HIV Drug Resistance Testing of Kenyans Before First-Line ART Michael H. Chung 1 ; Ingrid Beck 2 ; Molly Levine 2 ; Catherine Kiptiness 3 ; James Munyao 3 ; Rachel Silverman 1 ; Christine McGrath 1 ; Bhavna Chohan 1 ; Samah Rafie Sakr 3 ; Lisa Frenkel 2 1 Univ of Washington, Seattle, WA, USA; 2 Seattle Children’s Rsr Inst, Seattle, WA, USA; 3 Coptic Hope Cntr, Nairobi, Kenya Background: Testing for HIV drug resistance prior to initiation of ART has been found to be cost effective in high-resource communities and is recommended by advisory panels, but due to costs is not used in resource-limited communities. The prevalence of transmitted HIV drug resistance has increased in Kenya during the past ten years. We hypothesized that a relatively simple and inexpensive point mutation assay could identify HIV drug resistance in individuals qualifying for 1 st -line ART in Kenya, and that use of the test results to choose the ART regimen would improve virologic suppression after 12 months of treatment. Methods: A randomized clinical trial tested Kenyans qualifying for 1 st -line ART using a quantitative oligonucleotide ligation assay ( OLA ). Each subject randomized to OLA was tested at codons 103, 181, 184 and 190 in pol reverse transcriptase to detect and quantify mutations as <10% (not resistant) or ≥10% (resistant) within their quasispecies. Subjects randomized to receive pre-ART OLA with ≥1 resistance mutations were given 2 nd -line ART with lopinavir/rt, whereas each individual randomized to “no OLA” received standard of care ( SOC ) non-nucleoside reverse transcriptase based ART. Plasma HIV RNA was measured pre-ART, at 12 months of ART, and if >40c/mL, again at 15 months. Results: OLA was implemented at Coptic Hope Center in Nairobi. A total of 991 subjects enrolled into the study in 2013/14. The overall prevalence of resistance was 8.3%. The 12-month study was completed in November 2015. Testing for HIV drug resistance using a relatively simple and inexpensive point mutation OLA was feasible in Kenya. The OLA testing and initiation of 2 nd -line lopinavir/rt-based ART did not significantly impact the overall rate of virologic suppression (1 o outcome). Among individuals with resistance detected, rates of virologic suppression were improved by pre-ART OLA testing (2 o outcome). Conclusions: OLA testing for resistance did not improve rates of ART suppression at the population level. Because OLA testing improved outcomes of those with resistance, this study suggests that virologic failure was principally due to other factors. If rates of transmitted resistance continue to increase to increase in Kenya, OLA testing may positively affect overall rates of HIV suppression, and currently, identifying individuals with resistance and starting them on 2 nd -line lopinavir/rt-based ART may reduce transmission of drug resistance.

Poster Abstracts

495 More Efficacious Drugs Lead to Hard Selective Sweeps in HIV Drug Resistance Evolution Alison F. Feder 1 ; Soo-Yon Rhee 1 ; RobertW. Shafer 1 ; Dmitri A. Petrov 1 ; Pleuni S. Pennings 2 1 Stanford Univ, Stanford, CA, USA; 2 San Francisco State Univ, San Francisco, CA, USA

Background: In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many resistance mutations arise simultaneously, evolution of resistance proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if resistance mutations occur rarely in the population, then a single mutation can spread alone in a hard selective sweep. We look for genetic signatures to test the hypothesis that the transition from fast to slow evolution of drug resistance was accompanied by a transition from soft to hard selective sweeps. Methods: We examine 6,717 HIV-1 direct PCR sequences from patients treated with first-line therapies between 1989 and 2013 from the Stanford HIV Drug Resistance Database and determine genetic diversity and the number of drug resistance mutations for each sequence. We fit generalized linear models for each type of treatment to measure how a drug resistance mutations taking over the virus population in a patient affects viral population diversity. This effect should be small if resistance establishes via soft sweeps, but large and negative if hard sweeps predominate.

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CROI 2016