Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals.

INTRODUCTION: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. METHODS: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. RESULTS: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. CONCLUSIONS: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.

Accumulation of P(T/S)AP late domain duplications in HIV type 1 subtypes B, C, and F derived from individuals failing ARV therapy and ARV drug-naive patients.

HIV-1 budding requires short peptide motifs in p6(Gag), known as late domains, that promote the release of infectious virions. The primary late domain of HIV-1 is a Pro-(Thr/Ser)-Ala-Pro (hereafter referred to as a PTAP) motif. This motif may be completely or partially duplicated. In this work we analyzed p6(Gag) sequences from 547 isolates from drug-naive patients and 213 isolates from patients failing HAART therapy. Complete duplications within PTAP were selected during HAART therapy in all HIV-1 subtypes analyzed: B (p = 0.0338), F1 (p = 0.0294), and C (p = 0.0001). Nevertheless, the patterns of these duplications were different; subtype C isolates accumulated longer duplications and displayed a higher frequency of duplications in both treated (54%) and drug-naive isolates (23%). Accumulation of PTAP duplications within subtypes B, F1, and C during therapy suggests a potential role of the duplications in antiretroviral drug resistance.

Prevalence of etravirine-associated mutations in clinical samples with genotypic resistance to nevirapine and efavirenz in Brazilian clinics.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent and well tolerated. In Brazil, the first-generation NNRTI efavirenz is included in the majority of first-line antiretroviral treatment regimens. In this study, we evaluated the effectiveness of etravirine, a new second-generation NNRTI, among patients failing antiretroviral regimens containing first-generation NNRTIs. We assessed single resistance mutations to etravirine as well as complex resistance mutations profile and discuss the potential of introducing etravirine as salvage therapy.