Temporal dynamics of HIV-1 circulating subtypes in distinct exposure categories in southern Brazil.

BACKGROUND: The HIV-1 epidemic in Brazil is predominantly driven by subtype B. However, in Brazilian Southern region subtype C prevails and a relatively high AIDS incidence rate is observed. The aim of the present study was to assess the temporal dynamics of HIV-1 subtypes circulating in patients from distinct exposure categories in Southern Brazil. For this purpose 166 HIV-1 samples collected at the years of 1998 (group I) and 2005-2008 (group II) were analyzed. RESULTS: Analysis of group I revealed statistically significant (p < 0.05) associations between MSM and subtype B as well as between IDU and subtype C; while no statistical significant association between HIV-1 subtypes and exposure category was verified for group II. An overall temporal increase in the prevalence of subtype C and BC recombinants was observed in both HET and MSM populations, accompanied by a proportional decrease in the prevalence of the pure subtype B. CONCLUSIONS: The present study shows an association between HIV subtypes and exposure categories at the middle 1990s in Southern Brazil. Our findings suggest that MSM and IDU populations might have played a major role in the introduction and initial dissemination of subtypes B and C, respectively, in Southern Brazil. This study also suggests a trend towards homogenization of HIV-1 strains across distinct exposure categories as a consequence of an overall increase in the prevalence of subtype C and BC recombinants in both HET and MSM populations.

HIV-1 genetic diversity and drug resistance among treatment naïve patients from Southern Brazil: an association of HIV-1 subtypes with exposure categories.

BACKGROUND: The AIDS epidemic in Southern Brazil has unique features, showing co-circulation of HIV-1 subtypes C, B and recombinant forms. Florianópolis has the second highest AIDS incidence among Brazilian capitals, but limited information is available about HIV molecular epidemiology and prevalence of primary drug resistance. OBJECTIVES: To investigate the molecular epidemiology of HIV-1 in Florianópolis and to describe the prevalence of primary HIV-1 drug resistance mutations (DMRs). STUDY DESIGN: Epidemiological and clinical data from 82 untreated patients from Florianópolis (2008-2009) were analyzed. The HIV-1 subtype at envelope, protease, reverse transcriptase and integrase regions were determined by phylogenetic and bootscaning analyses and the drug resistance profile were analyzed at the Stanford HIV Drug Resistance Database. RESULTS: The most frequent HIV-1 genetic form was subtype C (65.8%) followed by mosaics BC (18.3%), subtype B (13.4%), subtype F1 (1.2%) and BCF1 recombinant (1.2%). HIV-1 subtype C and BC recombinants were much more frequent in the heterosexual exposure category, whereas subtype B was more common in the MSM exposure category. DRMs were seen in 11% of the sequences, 2.4% of them were related to PI, 5% to NRTI, 3.6% to NNRTI and 1.2% was related to INTI. CONCLUSIONS: The present study confirms the high prevalence of subtype C and BC recombinants in Santa Catarina State and revealed a significant difference in the subtype distribution among distinct virus exposure categories. This study also shows a relative high prevalence of protease/reverse transcriptase primary drug resistance mutations and corroborates the usefulness of the integrase inhibitors in southern Brazil.

The nerve growth factor reduces APOBEC3G synthesis and enhances HIV-1 transcription and replication in human primary macrophages.

Macrophages infected with HIV-1 sustain viral replication for long periods of time, functioning as viral reservoirs. Therefore, recognition of factors that maintain macrophage survival and influence HIV-1 replication is critical to understanding the mechanisms that regulate the HIV-1-replicative cycle. Because HIV-1-infected macrophages release the nerve growth factor (NGF), and NGF neutralization reduces viral production, we further analyzed how this molecule affects HIV-1 replication. In the present study, we show that NGF stimulates HIV-1 replication in primary macrophages by signaling through its high-affinity receptor Tropomyosin-related Kinase A (TrKA), and with the involvement of reticular calcium, protein kinase C, extracellular signal-regulated kinase, p38 kinase, and nuclear factor-κB. NGF-induced enhancement of HIV-1 replication occurred during the late events of the HIV-1-replicative cycle, with a concomitant increase in viral transcription and production. In addition, NGF reduced the synthesis of the cellular HIV-1 restriction factor APOBEC3G and also overrode its interferon-γ-induced up-regulation, allowing the production of a well-fitted virus. Because NGF-TrKA signaling is a crucial event for macrophage survival, it is possible that NGF-induced HIV-1 replication plays a role in the maintenance of HIV-1 reservoirs. Our study may contribute to the understanding of the immunopathogenesis of HIV-1 infection and provide insights about approaches aimed at limiting viral replication in HIV-1 reservoirs.

Short communication: Evidences of recent decline in the expansion rate of the HIV type 1 subtype C and CRF31_BC epidemics in southern Brazil.

The HIV-1 epidemic in southern Brazil is characterized by the high prevalence of subtype C and CRF31_BC infections but little is known about the population dynamics of these strains over time. We used a total of 82 env and 72 pol HIV-1 subtype C sequences collected from 1991 to 2006 and 47 pol CRF31_BC sequences collected from 1998 to 2006 from Brazilian patients to reconstruct the demographic history of these HIV-1 strains. Estimations of demographic history were performed using a Bayesian Markov Chain Monte Carlo coalescent-based approach as implemented in the BEAST program. Our analyses indicate that subtype C and CRF31_BC epidemics experienced an initial period of fast exponential spread in the southern Brazilian population during the 1980s and early 1990s, but the spreading rate of these epidemics seems to have slowed down since the middle 1990s. The initial mean exponential growth rate of the subtype C epidemic was estimated to be around 0.70-0.90/year, whereas the estimated population growth rate of CRF31_BC was 1.3/year, more than two times higher than that previously described for this CRF. These results suggest for the first time that the growth rate of subtype C and CRF31_BC epidemics has been changing over time in southern Brazil with evidence for a deceleration in recent years. During the expansion phase, the CRF31_BC seems to have spread at a rate much higher than Brazilian parental subtypes B and C.