HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations in Female Sex Workers from a Brazilian Municipality in the Amazon Region

Editor: Acquired and transmitted HIV drug resistance is public health concern, and persons carrying HIV with drug resistance mutations are at a higher risk of virological failure. Therefore, monitoring of risk behavior and testing for drug resistance among high-risk groups are important. Female sex workers (FSWs) are a group at high risk for the acquisition of HIV due to their social vulnerability and the risks associated with their occupation. Recently, the highest prevalence of HIV infection in South America among FSWs was recorded in the municipality of Bragança (Brazilian state of Pará, Amazon region), and none of the women were aware of HIV infection. ¹ This letter described the prevalence and profile of resistance to antiretroviral drugs and of HIV-1 genetic diversity among FSWs in the municipality of Bragança, in the Amazon region (northern Brazil).

Among 137 FSWs accessed through respondent-driven sampling, 21 women had positive diagnosis of HIV-1 by real-time polymerase chain reaction. ¹ All cDNA HIV samples were subjected to amplification and nucleotide sequencing (∼1,000 nucleotides of the pol gene encompassing the entire protease and part of the reverse transcriptase region), from which subtypes and transmitted drug resistance mutations (TDRMs) were determined, and the effect of these mutations on drug resistance was predicted and classified as previously described. ^2,3 Sequences identified by the Calibrated Resistance Population (CPR) tool as having surveillance DRM 2009, but classified as susceptible or potentially low-level resistant by the HIVdb Program version 8.8 (https://hivdb.stanford.edu), were not considered resistant for transmitted resistance rate estimation.

The phylogenetic analyses showed that most of the samples were subtype B (81.0%, 17/21), followed by subtype F1 (9.5%, 2/21) and recombinant form BF1 (9.5%, 2/21). The prevalence of TDRMs was 47.6% (10/21). Mutations associated with resistance to nucleoside analogue reverse transcriptase inhibitor (NRTI) were most frequent (42.9%, 9/21), followed by mutations associated with resistance to non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs) (14.3%, 3/21) and protease inhibitors (PIs) (9.5%, 2/21). In addition, three sequences were related to resistance to NRTI+NNRTI and two sequences to resistance to NRTI+PI. A variable spectrum of drug resistance was observed in nine HIV-1 sequences detected in FSWs, including five sequences (FSW02, FSW03, FSW08, FSW11, and FSW19) indicated with resistance to many antiretroviral drugs. All mutations found in this study are listed in Table 1 according to the HIV-1 subtype and resistance to antiretroviral drugs. All FSWs with some TDRM offered sexual services in street markets, town squares, street corners, bars, and gas stations in the municipality of Bragança, and were not aware of carrier status until participation in this study.

In the Amazon region, there are very few studies on drug resistance mutations in people with HIV-1. This study is one of the first reports that identified subtypes and TDRMs in FSWs infected with this virus. The distribution of viral subtypes is consistent with information from the Brazilian states of the Amazon region. ^{2 –4} However, the rate of TDRMs detected in this study is much higher than the values recorded in the states of Amapá (1.0%), ² Amazonas (16.2%), ³ Pará (10%), ⁴ Roraima (8.3%), ⁴ and Tocantins (11.5%). ⁴ K103N and M184V mutations were the most prevalent in this study. They confer resistance to NRTIs and NNRTIs and were detected in 3 of 10 HIV-infected FSWs. The double mutants found for these two drug classes consist uniquely of this combination and appear in different subtypes, discarding the possibility of a transmission cluster. K103N and M184V mutations have been reported with high prevalence in studies conducted with people living with HIV/AIDS in the Amazon region. ^2,4,5

Among the FSWs, HIV-1 is being spread through unprotected sex associated with conditions of socioeconomic vulnerability, ¹ as aggravating some strains also have TDRMs. This scenario is very worrying and should alert health authorities in Brazil. Planning and immediate implementation of measures for HIV-1 control and prevention are required. Over time this could create a major public health problem in the Amazon region, an underdeveloped area, with high levels of poverty, limited transport infrastructure, and inadequate health services.