CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: We describe a cluster of 76 individuals with primary transmitted NNRTI resistance to HIV in southern Saskatchewan, characterized by disproportionate transmission through injection drug use in Aboriginal peoples and high rates of hepatitis C co-infection. This represents a microcosm of the current provincial HIV epidemic. Similar transmission clusters are occurring elsewhere across the province, both in urban and on-reserve settings, where prevalence of injection drug use is high. These transmission dynamics, complicated further by social, cultural and geographic factors, require urgent attention and mobilization of public health and clinical resources.

599 Transmitted Drug Resistance and Time of HIV Infection, New York State, 2006-2013 ZhengyanWang 1 ; EmilyWalits 2 ; Daniel E. Gordon 1 ; Bridget J. Anderson 1 ; Deepa Rajulu 1 ; LingWang 1 ; Lou C. Smith 1 1 New York State Department of Health, Albany, NY, US; 2 University at Albany, School of Public Health, Albany, NY, US

Background: The date of HIV infection cannot be readily established for most HIV cases. Resistance results for persons newly diagnosed with HIV infection may reflect transmissions that occurred years earlier. This study evaluates the need to classify newly diagnosed cases by recency of infection in order to accurately determine the prevalence of transmitted drug resistance (TDR) and assess variation in TDR prevalence across demographic and risk groups in New York State (NYS). Methods: Newly diagnosed cases 1/2006-9/2013 age ≥ 13 years in the NYS HIV surveillance registry were classified as “recent” or “longstanding” infections based on BED test results. Absent a BED result, cases with an AIDS diagnosis at or within 6 months of HIV diagnosis were classified as longstanding; all others were classified as “unknown.” All cases were linked with clinical genotypic resistance test results routinely reported to NYS Department of Health (NYSDOH). Tests within 3 months of the HIV diagnosis date were considered “initial” resistance tests and were included in the analyses. Mutations in protease (PR) and reverse transcriptase (RT) gene sequences were compared to CDC’s Transmitted Drug Resistance Mutation (TDRM) list to assess the presence of TDRMs. Prevalence ratios (PR) of TDRM between recent and longstanding cases were examined. Results: Among 29,000 newly diagnosed cases, 13,015 (44%) had a resistance test within 3 months of diagnosis. 2,016 (15%) were classified as recent, 8,703 (67%) as longstanding and 2,296 (18%) as missing. Demographic and resistance results for the “missing” group were similar to those for the combined recent and longstanding groups. The rate of TDR among recently infected cases rose from 17% in 2006 to 24% in 2013, from 13% to 18% in cases with longstanding infection and from 13% to 19% in all cases regardless of recency. Prevalence of TDRM was significantly higher among recently infected (19% versus 15%; PR: 1.29, 95% CI: 1.16-1.43) across all subgroups - sex, age, race/ethnicity, risk, and geographic location. Conclusions: Recency of infection is an important covariate of TDR prevalence among persons newly-diagnosed with HIV. Increasing TDR prevalence among recently infected cases suggests a growing number of transmissions are due to non-ARV naïve persons with poorly controlled infections. Lower TDR prevalence seen in longstanding cases in all years supports this, though overgrowth of resistant strains by wild-type virus over time would also contribute to that group’s lower TDR rate. 600 Transmitted HIV Drug Resistance Among Early Infected Persons in San Diego, California Theppharit Panichsillapakit 1 ; David M. Smith 2 ; JoelWertheim 2 ; Douglas D. Richman 2 ; Susan Little 2 ; Sanjay Mehta 2 1 Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2 University of California San Diego (UCSD), La Jolla, CA, US Background: Transmitted HIV drug resistance (TDR) continues to be an important issue, particularly for the initiation of antiretroviral therapy (ART). This study determined the prevalence and phylogenetic relationships of TDR among ART-naïve, HIV-infected individuals in San Diego County from 1996-2013. Methods: Retrospective analysis of the University of California, San Diego Primary Infection Resource Consortium from 1996 through 2013 was performed. Data were analyzed from 690 participants who underwent genotypic resistance testing before initiating therapy. Mutations associated with TDR were identified according to the WHO-2009 surveillance list. Clustering analysis of the HIV-1 pol sequence was performed using a network approach in which putative linkages were inferred when the TN93 genetic distance between two sequences was less than 1.5% substitutions per site. Results: The overall prevalence of TDR was 16.2% [112/690; 95% confidence interval (CI): 13.6-19.2] with a significant increase throughout the study period ( p for trend = 0.009). TDR was predominantly observed for resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) [10.1% (70/690); 95% CI: 8-12.7] and significantly increased over time ( p for trend < 0.001). TDR to nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 5.5% (38/690; 95% CI: 4-7.6) and 4.9% (34/690; 95% CI: 3.5-6.9) respectively, and changed minimally over time. Two and three-class TDR was prevalent at 4.8% and 0.9%, respectively. Among all the individuals with TDR, a total of 219 major and 6 minor TDR mutations were detected. TDR prevalence did not differ according to age, gender, race/ethnicity or risk exposure. 103 transmission clusters were identified of which 11 included at least two individuals sharing the same resistance mutation, accounting for 23.7% of the individuals with TDR.

Poster Abstracts

Conclusions: Between 1996 and 2013, the prevalence of TDR to ART (NNRTIs in particular) significantly increased among ART-naïve individuals with recent HIV-1 infection in San Diego. We found evidence of spread of these drug resistance mutations within transmission clusters of recently infected individuals. These findings continue to highlight the importance of baseline resistance testing to guide healthcare providers to select appropriate therapeutic options and to continue surveillance for drug resistance.

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CROI 2015