HIV-1 Transmitted Drug Resistance Mutations in Recently Diagnosed Antiretroviral-Naive Patients in Belém,Pará,Northern Brazil

EDITOR: The access to antiretroviral therapy (ART) has been offered universally in Brazil and has been very successful in reducing morbidity and mortality in patients infected with HIV-1. In recently diagnosed and ART-naive individuals, the treatment may be compromised if viral variants that are resistant to antiretroviral drugs were transmitted before the ART use. The development of primary ART resistance is related to virologic failure when treatment is started and can lead to the transmission of resistant strains. ¹ The objective of this study was to perform a cross-sectional study of the HIV-1 subtypes and rate of transmitted drug resistance mutations (TDRM) among recently diagnosed and ART-naive HIV-infected patients from Belém, Pará, Amazon Region of Brazil.

The HIV-1 protease and partial reverse transcriptase regions of 40 ART-naive patients from Belém, Pará, were sequenced between May and September of 2016. The calibrated population resistance and Stanford HIV Database Genotyping Resistance Interpretation (GRI-HIVdb) identified transmitted drug resistance mutations to the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI)/nonnucleoside reverse transcriptase inhibitor (NNRTI). The median age was 36 years old and men predominated (72.5%) with 47.5% heterosexual transmission, 30.0% men who have sex with men (MSM), and the first positive HIV serology at a median of 63 days. The prevalence of TDRM was 10.0% (four patients) based on the Surveillance Drug Resistance Mutation (SDRM) criteria table of mutations and 15.0% (six patients) based on GRI-HIVdb version 8.2 (https://hivdb.stanford.edu). Mutations associated with resistance to NRTIs were most frequent (5.0%; 2/40; including mutations M184I, M41L, and T215E). The prevalence of NNRTIs was 2.5% (1/40; mutation K103N) and to PIs was 2.5% (1/40; mutations M46I and I85V). Two out of four subjects with mutations based on the SDRM criteria were MSM and two were heterosexual women. Based on current Stanford HIVdb classification, five patients showed resistance to NNRTI (V108I, M230I, E138A, and V179D) and one showed resistance to PI (A71V). Resistance was not observed for two or three classes of drugs simultaneously.

In Brazil, most TDRM studies come from the southern region. Only three articles have been written in Northern Brazil, one from Tocantins, ² one from Amapá, ³ and one from Roraima, ⁴ demonstrating lack of information about TDRM on this region. Comparing the results obtained in four states in the Amazon region, it was observed similar prevalence of TDRM in Pará (10.0%; 4/40), Tocantins (11.5%; 6/52), and Roraima (8.3%; 1/12), but higher than the results observed at Amapá (1.0%; 1/97). This could be related to low access to ART, or a late introduction of ART on the results in Roraima and Amapá. Concerning the TDRM, there have been found similar results between Pará and Tocantins State, whereas at Amapá and Roraima were observed only mutations K103 and G190A to NNTRI, respectively.

This is the first study about TDRM in Pará and reveals a moderate rate of TDRM comparable to that observed in other major Brazilian cities. This preliminary data may subsidize the monitoring of the HIV evolution, and it is important to improve control strategies in the Amazon Region of Brazil.