1. Linking HIV-1 and Antiretroviral Drug Resistance Surveillances: Low Prevalence of HIV-1 Drug Resistance in Peru Lama JR 1, Suarez L 2, Laguna A 3, Acuña M 1, Olson J 3, Sanchez JL 4, Celum C 5, Sanchez J 1, Grant RM 6 Linking HIV-1 and Antiretroviral Drug Resistance Surveillances: Low Prevalence of HIV-1 Drug Resistance in Peru Lama JR 1, Suarez L 2, Laguna A 3, Acuña M 1, Olson J 3, Sanchez JL 4, Celum C 5, Sanchez J 1, Grant RM 6 1 IMPACTA, 2 Office of General Epidemiology, Ministry of Health of Peru, 3 US Naval Medical Research Center Detachment; in Lima, Peru, 4 US Military HIV Research Program, 5 University of Washington, 6 Gladstone Institute of Virology and Immunology, University of California, San Francisco; USA  Introduction: Until 2002, access to antiretroviral treatment (ART) in Peru had been restricted to patients who could afford for it, and mainly available in Lima. To determine the prevalence and patterns of antiretroviral drug resistance among MSM participating in a HIV-1 sentinel surveillance in Peru.  Methods: In 2002, HIV surveillance was conducted in 6 Peruvian cities (Lima, Sullana, Piura, Arequipa, Pucallpa and Iquitos). Further testing for mutations on the HIV-1 RT and protease gene sequences conferring drug resistance were conducted in stored plasma specimens from HIV- diagnosed participants (ViroSeq HIV-1 Genotyping System; Celera/Abbott Laboratories). There was no effort to over-sample HIV-1 infected persons to assess HIV-1 and/or genotypic resistance prevalences.  Results: HIV-1 infection was diagnosed in 456 (13.9%) of 3,280 participants. Prevalences differed by city, being highest in Lima (22.3%). Sequencing was completed in plasma samples from 375 (82.2%) participants. Nationwide, drug resistance was detected in 3.3% of 359 drug- naïve and 31.3% of 16 drug-experienced participants. Among chronically treatment naïve participants from Lima, resistance to one or more NRTI was 3.0% and 2.5% for PI. Drug resistance to any drug class was 3.9% among treatment-naïve and 38.5% among treatment-experienced MSM from Lima. The most frequently observed mutations in chronically treatment-naïve infected MSM from Lima were M184V (1.7%), D30N (1.3%), L90M (1.3%) and L10I (1.3%) –patterns which reflect treated populations derived from the same sampling frame.  Conclusions: The prevalence of HIV-1 drug resistance in Peru is low, reflecting the low treatment rates documented in this surveillance, and the high frequency of wild-type drug failure among treated persons. We demonstrate how drug resistance surveillance can be integrated into national HIV-1 sentinel surveillance. Our findings prior to nationwide ART roll-out, currently being conducted in Peru, contrast with the history of ART in developed countries, where high levels of NRTI resistance occurred prior to introduction of ART. Abstract Introduction  In all countries of the Andean Region, men who have sex with men (MSM) account for the largest proportion of HIV-infected cases.  Until the recent Ministry of Health antiretroviral “roll-out” program in Peru, for the minority of HIV-infected persons who have had access to treatment, partially effective and non-suppressive therapies have been commonly used, driven by costs, accessibility, short term clinical outcomes, and humanitarian reasons, which has raised concerns about the public health implications for transmission of HIV-1 resistant strains.  If resistance is high, it could comprise the effectiveness of the current expanded program of antiretroviral therapy.  HIV-1 Sentinel Surveillance has been biannually conducted among MSM in different Peruvian cities since 1996.  To determine the prevalence of HIV-1 drug resistance, we linked antiretroviral drug resistance surveillance with HIV-1 sentinel surveillance among MSM in six different Peruvian cities: Lima, Piura, Sullana, Arequipa, Iquitos and Pucallpa, in 2002. Objective Methods Study Population  Consecutive men older than 17 years of age, who had had sexual intercourse with one or more men during the previous year, were eligible to participate, regardless of history of HIV-1 testing or serostatus. There was no effort to over-sample HIV-infected persons in order to assess the HIV or drug resistance prevalence.  Recruiters and peer educators, representing the diverse Peruvian MSM sub-cultures, visited different and previously mapped venues referring potential participants to sentinel sites.  Cities were chosen based on higher HIV-1 prevalence and incidence relative to other Peruvian cities, based on the 2000 HIV-1 Sentinel Surveillance. Activities were conducted over a 3-month period in each city. Results  A total of 3,280 MSM met entry criteria and accepted participation. HIV and STI prevalences are shown in Table 1.  Sequencing was completed in plasma samples from 375 (82.2%) of the 456 HIV-1 infected participants.  Drug resistance to one or more classes of antiretroviral drugs was detected in plasma specimens of 3.3% of the 359 drug-naïve and 31.3% of the 16 drug-experienced HIV-1 infected participants with successful genotyping (Table 2).  Among treatment-naïve, chronically HIV-1 infected participants from Lima, the observed prevalence of resistance to one or more drug within each drug classes range from 3.0% for NRT to 2.5% for PI. No resistance to NNRTI among treatment-naïve men.  The overall prevalence of drug resistance to any drug class was 3.9% among drug-naïve participants from Lima and 38.5% among treatment-experienced MSM in Lima.  Among treatment-experienced HIV-1 infected participants, the prevalence of resistance to any NRTI was 38.5%, to NNRTI 7.7%, to PI 23.1%. In cities other than Lima, resistant strains were only observed in two treatment-naïve participants from Sullana, and those viruses with mutations that confer resistance to NNRTIs (K103N mutations present).  High HIV and STI prevalences are observed among MSM in diverse Peruvian cities.  The prevalence of HIV-1 drug resistance in Peru is low, reflecting the low treatment rates documented in this surveillance, and the high frequency of wild-type drug failure among treated persons.  We demonstrate how drug resistance surveillance can be integrated into national HIV-1 sentinel surveillance. Our findings prior to nationwide ART roll-out, currently being conducted in Peru, contrast with the history of ART in developed countries, where high levels of NRTI resistance occurred prior to introduction of ART.  Our findings indicate the need for further HIV-1 drug resistance monitoring once the use of antiretrovirals has been expanded, in Lima and in other Peruvian cities, which might further inform drug selection and resistance testing policies. Conclusions Laboratory Procedures  A venous blood sample was obtained for detection of antibodies to HIV-1 (ELISA with confirmation by and Western Blot), Treponema pallidum (RPR with confirmation by MHA-TP) and to HSV-2 (ELISA, IR > 3.5). The sensitive/less sensitive HIV EIA approximation was used to detect recent HIV infection. Estimated HIV incidences and 95% CIs were computed  Plasma was separated from whole blood samples in all participants diagnosed with HIV-1 infection and then aliquoted and stored at -80°C.  The ViroSeq™ HIV-1 Genotyping System (Celera/Abbott Laboratories) was used to assess the presence of genomic mutations, by sequencing of the entire protease gene and two-thirds of the reverse transcriptase gene. 1.The proposed research is in a well defined area. 2.The samples are population-based allowing estimates of population prevalence of drug resistance in treated and untreated persons. 3.Persons at high and medium risk for transmitting HIV-1 are included in the targeted well-studied sample, allowing estimates to be weighted to individual sexual behaviors, networks, and aggregate population risk behaviors. Advantages of this Methodology over Existing Studies on the Epidemiology of Drug Resistance: