CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

601 HIV Molecular Epidemiology and Transmitted Drug Resistance in the Mesoamerican Region Claudia Garcia-Morales 1 ; Santiago Avila-Rios 1 ; DanielaTapia-Trejo 1 ; Carlos Mejía-Villatoro 2 ; Juan M Pascale 3 ; Guillermo Porras-Cortes 5 ; Ivette Lorenzana 4 ; Elsa Palou 4 ; Marvin Manzanero 6 ; Gustavo Reyes-Terán 1 1 National Institute of Respiratory DIsease, Mexico City, Mexico; 2 Roosevelt Hospital, Guatemala City, Guatemala; 3 Gorgas Memorial Institute for Health Studies, Panama City, Panama; 4 Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras; 5 Vivian Pellas Metropolitan Hospital, Managua, Nicaragua; 6 Ministry of Health, Belize City, Belize Background: Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access. We present preliminary results from a large study to assess HIV TDR and viral diversity in Mexico and Central America. Methods: HIV-infected ART-naïve individuals fromMexico (n=1476), Guatemala (n=1180), Panama (n=238), Nicaragua (n=222), Honduras (n=294) and Belize (n=100) were enrolled from October 2010 to July 2014. Plasma HIV pol sequences were obtained. HIV subtyping was performed with REGA Subtyping Tool v2 and RIP 3.0, available on line. TDR was assessed using the WHO TDR surveillance mutation list. Results: Belize showed the highest global TDR prevalence (19.0%), followed by Nicaragua (14.9%), Panama (12.2%), Honduras (9.9%, p=0.02), Mexico (7.7%, p=0.0005) and Guatemala (7.1%, p=0.0002). TDR to NNRTIs was higher compared with NRTIs and PIs in Guatemala (4.6%, 1.8% [p<0.0002] and 1.1% [p<0.0001] respectively), Panama (9.2%, 3.8% [p=0.02] and 0.8% [p p<0.0001]), Honduras (6.5%, 2.0% [p=0.01] and 2.2% [p=0.01]) and Belize (18.0%, 1.0% [p<0.0001] and 1.0%[p<0.0001]). Belize showed higher TDR to NNRTIs than Panama (p=0.02), Nicaragua (p=0.002), Honduras (p=0.001), Guatemala (p<0.0001) and Mexico (p<0.0001). Nicaragua showed higher TDR to NRTIs than Panama (p=0.04), Belize (p=0.01), Honduras (p=0.0008), Mexico (p=0.0005), and Guatemala (p<0.0001). In all countries, clusters of drug-resistant viruses were observed. The TDR mutations identified in clusters were M46IL and L90M to PIs, M41L and T215X to NRTIs and K103NS and G190A to NNRTIs. Considering individuals in early chronic stage (>500 CD4+ T cells/uL) vs. late chronic stage (<350 CD4+ T cells/uL) global TDR in Mexico was 9.7% vs 6.5% (p=0.02), and in Guatemala 9.3% vs 6.6% (p=0.0305). HIV subtype B was highly prevalent in Mexico (97.1%), Guatemala (94.5%), Panama (95.0%), Nicaragua (95.9%), Honduras (94.9%) and Belize (67.4%). Country-specific viral clusters were highly frequent, suggesting an important role of cultural and geographic barriers for HIV dispersion in the region. Conclusions: The global TDR prevalence in Mexico, Guatemala, Panama, Nicaragua and Honduras remains at the intermediate level, but is high in Belize. Different epidemiologic scenarios can be observed in different Mesoamerican countries warranting local HIV molecular epidemiology and TDR surveillance studies. 602 Temporal Trends of Transmitted HIV Drug Resistance Following Seroconversion Ashley Olson 1 ; Claudia Kucherer 3 ; Anders Sönnerborg 4 ; Carmen de Mendoza 5 ; Robert Zangerle 6 ; Maria Prins 9 ; John Gill 2 ; Anne-Marte Bakken Kran 7 ; Dimitrios Paraskevis 8 ; Kholoud Porter 1 for CASCADE collaboration in EuroCoord 1 University College London, London, United Kingdom; 2 University of Calgary, Alberta Health Services, Calgary, Canada; 3 Robert Koch Institute, Berlin, Germany; 4 Karolinska Institutet, Stockholm, Sweden; 5 Puerta de Hierro Research Institute and University Hospital, Madrid, Spain; 6 Innsbruck Medical University, Innsbruck, Austria; 7 Oslo University Hospital, Oslo, Norway; 8 University of Athens, Athens, Greece; 9 Public Health Service of Amsterdam, Amsterdam, Netherlands Background: Transmitted drug resistance (TDR) may increase with wider use of cART and can contribute to cART failure. We aim to analyse the time trends of TDR among HIV seroconverters. Methods: Using CASCADE data, we considered nucleotide sequences from ART naïve individuals collected in the cART era (>1996) from samples taken within one year of HIV seroconversion (SC) and identified the most commonly observed (>10%) transmitted mutations by drug class according to the WHO criteria (SDRMs). The virus was considered resistant if a SDRMmutation was present. Using logistic regression, we examined the association between TDR and calendar time (modelled linearly), sex, transmission risk group, acute HIV infection (laboratory evidence of SC or HIV test interval < 30 days) and SC age. To allow 1 year of sample collection after HIV SC, we considered individuals seroconverting until 31 December 2012. Results: Of 4183 eligible individuals seroconverting 1996-2012 (median 2007), 3839 (92%) were male. Median (IQR) age at SC was 33 (27, 39) and mode of infection was mainly sex between men, 3341 (80%). HIV Subtype was predominantly B, 3041 (73%), followed by A, 315 (8%), C, 263 (6%), and CRF02_AG, 84 (2%). Time from SC to sample collection was similar in those with and without TDR, median = 94 (33, 185) days. Overall, 457 (11%) individuals had ≥ 1 WHO defined mutation; 251 individuals with NRTI mutations, most commonly at 41L (31%), 215S (21%), 215D (15%) and 184V (12%); 157 individuals with NNRTI mutations, most commonly at 103N (66%); and 125 individuals with PI mutations, most commonly at 90M (26%), 46I (22%), 46L (17%), 82A (13%) and 85V (10%). There was evidence of decreasing TDR to any class from 1996-2012 (OR (95% CI) = 0.918 (0.895, 0.942), p < 0.001) per year increase). The same decreasing trend was seen with NRTIs (OR = 0.881 (0.853, 0.911), p<0.001), NNRTIs (OR = 0.965 (0.925, 1.008), p = 0.11) and PIs (OR = 0.915 (0.874, 0.958), p <0.001). There was moderate evidence of an increased risk of TDR with acute infection (OR = 1.18 (0.96, 1.46), p=0.12). Conclusions: Transmitted drug resistance has decreased over calendar time. Moderate evidence of an association between TDR and acute infection may suggest TDR impacts SC illness or that we underestimate TDR if not tested immediately following SC. Our study provides a realistic estimate about the temporal trend of TDR due to inclusion of individuals with recent infection. 603 Increase in HIV Primary Drug Resistance in a Demographic Surveillance Area in Rural KwaZulu-Natal South Africa Justen Manasa; Siva Danaviah; FrankTanser; Sureshnee Pillay; Hloniphile Mthiyane; EduanWilkinson; Deenan Pillay; Tulio de Oliveira University of KwaZulu-Natal, Durban, South Africa Background: Increased access to antiretroviral therapy (ART) has been associated with significant reductions in AIDS related morbidity and mortality as well as a significant reduction in HIV incidence. As more patients access ART, higher proportions of newly infected patients is expected to be infected with drug resistant viruses in resource limited settings. Methods: Samples from treatment naïve participants from 3 rounds of an annual population based HIV surveillance programme in rural Kwazulu-Natal were genotyped for drug resistance. The sample types included, EDTA microtubes (2010) and DBS (2011 and 2012). Samples were selected from the population for 2010, 2011 and 2012 with an estimated duration of infection. In addition, we randomly selected samples from chronically infected drug naive individuals with VL > 10,000 copies/ml (2011 and 2012). The quality of sequences was assessed using the Calibrated Population Resistance (CPR) tool and by phylogenetic reconstruction analysis using ML and NJ methods. The 2009 surveillance of drug resistance mutation (SDRM) list was used in the drug resistance analysis. All statistical analyses were undertaken using Stata 10. Results: We sequenced 701 treatment naïve individuals (success rate 86%); 67 (2010), 381(2011), and 253 (2012). This represents approximately 15% of the surveillance samples for 2011 and 2012. Men constituted 25% of the participants. The average age was 34 years and the median viral load was 116,600 RNA copies/ml. One or more SDRM were identified in 36 (5%) of the 701 participants. Of these, the NNRTI SDRMwere the most dominant, being detected in 32 (5%) samples. The most common were K103N, V106M and G190A, in 27 (3.8%), 3 (0.4%) and 2 (0.3%) samples respectively. Only 3 (0.4%) samples had 2 or more NNRTI SDRM. NRTI SDRM were detected in 11 (1.6%) of the participants, 9 of whom had only one NRTI SDRM. Six (1%) of the participants had both NNRTI and NRTI resistance mutations, K103N +M184V being the most common combination. There was no evidence of SDRM from the 2010 participants. The 2011 and 2012 samples both had 18 participants with some SDRM, 5% and 8% respectively. Conclusions: The NNRTI SDRMs are the major contributors to observed patterns of primary drug resistance. There is an increasing need to identify recently infected participants in order to better understand the trends in primary drug resistance in reponse to changes in treatment coverage and treatment regimens in public sector treatment programmes.

Poster Abstracts

381

CROI 2015