Evaluation of Antiretroviral Resistance in population of Men who have sex with Men in a Multicenter study in Brazil by Respondent Driven Sampling

O HIV-1 apresenta uma alta diversidade genetica, resultado principalmente de sua alta taxa de replicacao e das caracteristicas da atividade de sua Transcriptase Reversa. Existem poucos estudos sobre os subtipos de HIV e de resistencia transmitida e secundaria aos medicamentos antirretrovirais em amostras de homens que tem sexo com homens (HSH) no Brasil. Com a finalidade de estudar as caracteristicas virologicas, foram empregadas amostras de voluntarios das cinco regioes brasileiras selecionados atraves da metodologia de respondent driven sampling (RDS). Analisamos a diversidade genetica do HIV e a prevalencia de mutacoes associadas com resistencia antirretroviral em HSH nas cinco regioes geograficas do Brasil. Usando RDS foram recrutados e entrevistados 3.515 HSH em 10 cidades. Destes, 299 (9,5%) eram infectados com HIV e 178 concordaram em testes de genotipagem. Nos descrevemos neste trabalho os resultados de 162 amostras; os subtipos mais comuns foram: B (81,4%), C (7,4%), F (4,3%), D (0,6%) e formas recombinantes (6,2%). Especificamente de 143 pessoas cujas amostras foram adequadas para analise e tinham disponiveis dados epidemiologicos: 44 (30,8%) tinham recebido terapia antirretroviral (ART) (AE) e 99 (69,2%) eram ART-naive (AN). Apos o sequenciamento nas regioes da transcriptase reversa e protease do virus, a analise para mutacoes de resistencia foi feita usando os parametros da OMS. A prevalencia da resistencia primaria foi de 21,4%, isto e, entre os NA; e a de resistencia secundaria foi de 35,8% (isto e, entre os AE). A prevalencia de resistencia a inibidores de protease (IP) foi de 3,9% (AN) e 4,4% (AE); para inibidor da transcriptase reversa analogo de nucleosideos (NRTI) 15,0% (AN) e 31,0% (AE) e para inibidor da transcriptase reversa nao analogo de nucleosideos (NNRTI) 5,5% (AN) e 13,2% (AE). A mutacao de resistencia mais comum para NRTIs foi 184V (17 casos) e para NNRTIs: 103N (16 casos). Nossos dados sugerem um alto nivel de resistencia transmitida em HSH no Brasil. Estudos epidemiologicos desenhados para medir a prevalencia de resistencia primaria nesta populacao sao necessarios para identificar os correlatos e as causas da resistencia antirretroviral para poder limitar o desenvolvimento de resistencia nesta e outras populacoesBV UNIFESP: Teses e dissertaçõe

Antiretroviral Drug Resistance in a Respondent-Driven Sample of HIV-Infected Men Who Have Sex With Men in Brazil

Background: There are few studies on HIV subtypes and primary and secondary antiretroviral drug resistance (ADR) in community-recruited samples in Brazil. We analyzed HIV clade diversity and prevalence of mutations associated with ADR in men who have sex with men in all five regions of Brazil.Methods: Using respondent-driven sampling, we recruited 3515 men who have sex with men in nine cities: 299 (9.5%) were HIV-positive; 143 subjects had adequate genotyping and epidemiologic data. Forty-four (30.8%) subjects were antiretroviral therapy-experienced (AE) and 99 (69.2%) antiretroviral therapy-naive (AN). We sequenced the reverse transcriptase and protease regions of the virus and analyzed them for drug resistant mutations using World Health Organization guidelines.Results: the most common subtypes were B (81.8%), C (7.7%), and recombinant forms (6.9%). the overall prevalence of primary ADR resistance was 21.4% (i.e. among the AN) and secondary ADR was 35.8% (i.e. among the AE). the prevalence of resistance to protease inhibitors was 3.9% (AN) and 4.4% (AE); to nucleoside reverse transcriptase inhibitors 15.0% (AN) and 31.0% (AE) and to nonnucleoside reverse transcriptase inhibitors 5.5% (AN) and 13.2% (AE). the most common resistance mutation for nucleoside reverse transcriptase inhibitors was 184V (17 cases) and for nonnucleoside reverse transcriptase inhibitors 103N (16 cases).Conclusions: Our data suggest a high level of both primary and secondary ADR in men who have sex with men in Brazil. Additional studies are needed to identify the correlates and causes of antiretroviral therapy resistance to limit the development of resistance among those in care and the transmission of resistant strains in the wider epidemic.Ministry of Health/Secretariat of Health Surveillance/Department of STD, AIDS and Viral Hepatitis through Brazilian GovernmentMinistry of Health/Secretariat of Health Surveillance/Department of STD, AIDS and Viral Hepatitis through United Nations Office on Drugs and Crime-UNODCDepartment of STD, AIDS and Viral Hepatitis of the Ministry of HealthFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Ceara, Dept Saude Comunitaria, BR-60430971 Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilTulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USAUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Fed Bahia, Inst Saude Colet, BR-41170290 Salvador, BA, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv Brasilia, BR-70910900 Brasilia, DF, BrazilUniv Calif San Francisco, San Francisco, CA 94143 USAUniv São Paulo, LIM 03, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilMinistry of Health/Secretariat of Health Surveillance/Department of STD, AIDS and Viral Hepatitis through Brazilian Government: AD/BRA/03/H34Ministry of Health/Secretariat of Health Surveillance/Department of STD, AIDS and Viral Hepatitis through United Nations Office on Drugs and Crime-UNODC: AD/BRA/03/H34Department of STD, AIDS and Viral Hepatitis of the Ministry of Health: CSV 234/07FAPESP: 2004/15856-9CAPES: BEX 3495/06-0Web of Scienc