Moderate prevalence of HIV-1 transmitted drug resistance mutations in southern Brazil.

BACKGROUND: Despite the advances in therapy, the occurrence of drug-resistant human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful treatment. This study aimed to characterize the genetic diversity and to determine the prevalence of transmitted drug resistance mutations (TDRM) between individuals recently or chronically diagnosed with HIV-1 from Paraná, Brazil. METHODS: A total of 260 HIV-1 positive antiretroviral therapy-naïve patients were recruited to participate on the study, of which 39 were recently diagnosed. HIV-1 genotyping was performed using sequencing reaction followed by phylogenetic analyses to determine the HIV-1 subtype. TDRM were defined using the Calibrated Population Resistance Tool program. RESULTS: The HIV-1 subtypes frequency found in the studied population were 54.0% of subtype B, 26.7% subtype C, 6.7% subtype F1 and 12.7% recombinant forms. The overall prevalence of TDRM was 6.7%, including 13.3% for recently diagnosed subjects and 5.9% for the chronic group. CONCLUSIONS: The prevalence of resistance mutations found in this study is considered moderate, thus to perform genotyping tests before the initiation of antiretroviral therapy may be important to define the first line therapy and contribute for the improvement of regional prevention strategies for epidemic control.

HIV-1 molecular diversity in Brazil unveiled by 10 years of sampling by the national genotyping network.

HIV-1 has diversified into several subtypes and recombinant forms that are heterogeneously spread around the world. Understanding the distribution of viral variants and their temporal dynamics can help to design vaccines and monitor changes in viral transmission patterns. Brazil has one of the largest HIV-1 epidemics in the western-world and the molecular features of the virus circulating in the country are still not completely known. Over 50,000 partial HIV-1 genomes sampled between 2008 and 2017 by the Brazilian genotyping network (RENAGENO) were analyzed. Sequences were filtered by quality, duplicate sequences per patient were removed and subtyping was performed with online tools and molecular phylogeny. Association between patients' demographic data and subtypes were performed by calculating the relative risk in a multinomial analysis and trends in subtype prevalence were tested by Pearson correlation. HIV-1B was found to be the most prevalent subtype throughout the country except in the south, where HIV-1C prevails. An increasing trend in the proportion of HIV-1C and F1 was observed in several regions of the country, while HIV-1B tended to decrease. Men and highly educated individuals were more frequently infected by HIV-1B and non-B variants were more prevalent among women with lower education. Our results suggest that socio-demographic factors partially segregate HIV-1 diversity in Brazil while shaping viral transmission networks. Historical events could explain a preferential circulation of HIV-1B among men who have sex with men (MSM) and non-B variants among heterosexual individuals. In view of an increasing male/female ratio of AIDS cases in Brazil in the last 10-15 years, the decrease of HIV-1B prevalence is surprising and suggests a greater penetrance of non-B subtypes in MSM transmission chains.

Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil.

BACKGROUND: Antiretroviral drugs targeting integrase (IN) have recently been approved for use in combined and salvage therapeutic interventions. OBJECTIVE: To evaluate the presence of natural polymorphisms and resistance mutations associated with IN inhibitors among HIV-1 subtypes B, C, and F samples obtained from drug-naive individuals and patients failing highly active antiretroviral therapy in Brazil. METHODS: Proviral DNA was obtained from blood samples of 105 HIV-1-positive drug-naive patients infected by B, C, or F subtypes and plasma viral RNA from 30 subtype B-infected individuals failing highly active antiretroviral therapy. The IN region was amplified by nested polymerase chain reaction and automatically sequenced for subtype determination. Translated amino acid sequences were inspected for IN mutations associated with antiretroviral resistance. RESULTS: Eleven mutations described as conferring in vitro resistance to IN strand transfer inhibitors were detected among the HIV-1 Brazilian samples. V72I and V201I were considered as polymorphisms. Major mutations associated with elvitegravir or raltegravir in vivo resistance (Q148K/H/R, N155H) were not detected. CONCLUSIONS: Although some naturally occurring polymorphisms were observed, the absence of major resistance mutations for the current IN inhibitors provides a good rationale for the introduction of these drugs in Brazil. These results highlight the importance of the continuous surveillance of IN genetic diversity.

Contribuição ao estudo da diversidade do HIV-1 no Brasil: caracterização genotípica e fenotípica de amostras de HIV-1 obtidas em diferentes regiões geográficas / Contribution to the study of HIV-1 diversity in Brazil: genotypic and phenotypic characterization of HIV-1 samples obtained from different geographical regions

Desde o estabelecimento em cultura do primeiro isolado de HIV-l no Brasil (Galvão-Castro e cols., 1987), já podíamos perceber um polimorfismo genético e biológico em amostras obtidas no início da epidemia de AIDS no país, indicando que esta heterogeneidade seria similar a descrita para o HIV-l em outras partes do mundo (Couto-Fernandez e cols., 1992). Nos anos subsequentes, buscando um melhor detalhamento da estrutura genética destes isolados, entre outros, sequenciamos um fragmento genômico de aproximadamente 860pb correspondentes as regiões V3, V4, V5 e parte da gp41 do envelope viral de 6 amostras coletadas entre 1987 e 1989 (documento 1). A análise filo genética mostrou que estas amostras brasileiras eram do subtipo B, com níveis de diversidade variando entre 5,9 e 13, 1%. A análise das seqüências de aminoácidos da alça V3 revelou que 3 amostras possuíam o motivo GPGR no topo da alça, característico de isolados Norte Americanos/Europeus, enquanto que nas outras três existia uma substituição da prolina pelo triptofano (W), metionina (M) e fenilalalina (F), respectivamente. O grau de diversidade antigênica, avaliado pela reatividade sorológica de 114 soros obtidos de pacientes do Rio de Janeiro, coletados no período de 1990 a 1992, frente à diferentes peptídeos sintéticos subtipo-específicos, mostrou que 60,5% deles reagiram com peptídeos do subtipo B e 15,8% mostraram reatividade específica para o peptídeo Bra-cons (GWG). Um elevado percentual de soros (37,7%) não mostrou reatividade com os diferentes peptídeos usados. Buscando conhecer o espectro da diversidade do HIV-1 nos sítios selecionados para futuros testes de vacinas anti-HIV/AIDS, foi estabelecida a Rede Nacional de Laboratórios para Isolamento e Caracterização do HIV-1 no Brasil que, permitiu uma análise abrangente e sistematizada de amostras coletadas em diferentes regiões do país. Estes estudos, realizados primeiramente em amostras do Rio de Janeiro (documento 2) e, subseqüentemente,...