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

Abstract

IntroductionIn 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.MethodsThe 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.ResultsWe 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.ConclusionsTo 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.

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

“…However, these results differed from those of Sprinz et al and Murillo et al, who found a higher frequency of TDRMs for NNRTIs [11] and from other studies that found a higher frequency of TDRMs for NRTIs, then for NNRTIs and for PIs [13, 34]. The K103N TDRM was the most frequently found in this study and has been described in other studies conducted in different regions of Brazil [13, 33–35, 38]. The presence of this mutation is associated with high levels of resistance to NNRTI Nevirapine and Efavirens, which were part of the recommended regimen for initial therapy in HIV-1 infections at the time of sample collection.…”

“…The prevalence of TDRMs found in different studies varies according to the region and the population studied [27–31]. Based on the WHO HIVDR classification [32], the present study demonstrated a moderate level of resistance, which is in accordance to a recent survey conducted by Arruda et al that revealed moderate rate of TDRM in the five Brazilian macroregions [33]. Sax et al reported that in places where the prevalence of transmitted resistance is 1% or higher, testing for resistance before starting ART is considered cost-effective [5].…”

“…The frequency of HIV-1 subtypes varies according to the geographical region [39, 40]. The epidemiological profile of the different subtypes of HIV-1 in the country shows a clear predominance of subtype B, corresponding to about 75% of infected individuals [33, 36, 41–43]. Subtypes F and C are present in frequencies that differ from one region to another [36, 42, 43].…”

Detection of human immunodeficiency virus Type 1 phylogenetic clusters with multidrug resistance mutations among 2011 to 2017 blood donors from the highly endemic Northern Brazilian Amazon

“…In Manaus, 21.4% TDR was recently described among 117 newly diagnosed ARV‐naive children, in which 28.8% was previously exposed to mother‐to‐child ARV prophylaxis . A recent nationwide study with 1,558 patients showed 9.5% TDR and the 10.2% rate reported in the Northern region is similar to our findings . In 128 ARV‐naive, chronically infected blood donors (from Sao Paulo, Minas Gerais, Pernambuco, and Rio de Janeiro states), a high prevalence of TDR was detected in near full‐length HIV‐1 genomes obtained by ultradeep sequencing, which increases the detection of DRM .…”

HIV pretreatment drug resistance among cisgender MSM and transgender women from Lima, Peru

“…In the case of dolutegravir, the concern about possible neural tube defects would not be relevant in these populations . The risk of NRTI mutations remains low, even in comparison to Brazil , which recently reported a similar estimate for overall TDR but a threefold higher proportional risk for NRTI DRM. Our data therefore show little threat to the efficacy of NRTIs in current use in ART or as PrEP.…”