Despite the fact that subtype C appeared in southern Brazil more recently than subtype B, it is now the predominant strain in Rio Grande. The epidemic spread of subtype C could be taking place in Brazil, and possibly in south America, a phenomenon similar to that seen in other countries where this subtype is now totally dominant.

BackgroundAlthough extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood.Methods and FindingsWe wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naïve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher's exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI.ConclusionsThis is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.

BackgroundSubtype C is the most prevalent HIV-1 subtype in the world, mainly in countries with the highest HIV prevalence. However, few studies have evaluated the impact of antiretroviral therapy on this subtype. In southern Brazil, the first developing country to offer free and universal treatment, subtypes B and C co-circulate with equal prevalence, allowing for an extensive evaluation of this issue.Methods and FindingsViral RNA of 160 HIV-1+ patients was extracted, and the protease and reverse transcriptase genes were sequenced, subtyped and analyzed for ARV mutations. Sequences were grouped by subtype, and matched to type (PI, NRTI and NNRTI) and time of ARV exposure. Statistical analyses were performed to compare differences in the frequency of ARV-associated mutations. There were no significant differences in time of treatment between subtypes B and C groups, although they showed distinct proportions of resistant strains at different intervals for two of three ARV classes. For PI, 26% of subtype B strains were resistant, compared to only 8% in subtype C (p = 0.0288, Fisher's exact test). For NRTI, 54% of subtype B strains were resistant versus 23% of subtype C (p = 0.0012). Differences were significant from 4 years of exposure, and remained so until the last time point analyzed. The differences observed between both subtypes were independent of time under rebound viremia in cases of virologic failure and of the number of HAART regimens used by treated patients.ConclusionsOur results pointed out to a lower rate of accumulation of mutations conferring resistance to ARV in subtype C than in subtype B. These findings are of crucial importance for current initiatives of ARV therapy roll-out in developing countries, where subtype is C prevalent.

CRF31_BC plays an important role in the HIV epidemic of southern Brazil, and its prevalence has increased throughout the years. This circulating recombinant form corresponds to approximately 25% of total HIV isolates in this region in 2004. Understanding the cause of this spread is important for public health strategies in Brazil and in Latin America.

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 −1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 −1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

O objetivo deste estudo foi avaliar a prevalência de lesões bucais entre pacientes HIV positivos e identificar fatores associados a tais lesões. Foi realizado estudo transversal que coletou dados mediante entrevista, exame clínico e consulta aos prontuários médicos de pacientes adultos atendidos no Serviço de HIV-AIDS do Hospital Universitário da Universidade Federal do Rio Grande, Rio Grande do Sul, Brasil, sendo considerados fatores sócio-demográficos, imunológicos e terapêuticos. Foi utilizada a regressão de Poisson num modelo hierárquico de análise. Entre abril de 2006 a janeiro de 2007 foram observados 300 pacientes, sendo 51% do sexo masculino e média de idade de 40 anos; 39% apresentaram lesões bucais, sendo a candidíase a mais freqüente (59,1%), seguida de leucoplasia pilosa (19,5%). As mulheres apresentaram um risco menor, com observância de uma associação inversa com o CD4. Houve um risco maior entre aqueles pacientes com menor escolaridade, menor renda, tabagistas, dependentes do álcool, com maior tempo de infecção pelo HIV e carga viral mais elevada. Os dados confirmaram a elevada prevalência das manifestações bucais oportunistas e evidenciaram a sua relação com a situação social, assim como sua relação com determinados hábitos e costumes passíveis de modificação.

The aim of this study was to determine the rate and risk factors of HIV-1 mother-to-child transmission (MTCT), the timing of transmission and the transmitted subtype in a population where subtypes B and C co-circulate. One hundred and forty-four babies born to HIV-1-infected mothers were studied. Subtype and timing of transmission were determined by a nested polymerase chain reaction of the gp41 gene. Seven children were infected (4.9%): four were infected intrautero and one intrapartum. The higher frequency of intrautero transmission was statistically significant (P = 0.001). Use of antiretrovirals (ARVs) in the three stages of gestation was a protective risk factor for MTCT (PR = 0.42; CI: 0.21-0.83; P = 0.013). A higher HIV viral load at delivery was the only independent risk factor for MTCT. Early and universal access to ARVs during pregnancy are the most important measures to decrease vertical HIV-1 transmission even in areas where HIV clade distribution differs.

We conducted a molecular epidemiological study to investigate HIV-1 strains in Rio Grande, southern Brazil, searching for an association with transmission mode and risk behavior. Patients (185) identified at an AIDS treatment reference Hospital, from 1994 to 1997, were included; from which 107 blood samples were obtained. Nested PCR was realized once for each sample; for amplified samples (69) HIV subtypes were classified using the heteroduplex mobility assay. Subtypes identified were B (75%), C (22%) and F (3%). All infections with C were diagnosed after 1994. Comparing patients with B and C, no differences were detected regarding demographic, clinical and laboratory characteristics; survival analysis did not reveal differences in HIV to AIDS evolution. A higher proportion of injecting drug users, IDU (not significant, p<.07) was found among those with C. This suggests that C may have been introduced in this area through IDU, and is being spread, probably by their sexual partners, to persons with other risk practices.