A3 Brazilian network for HIV drug resistance surveillance: An investigation of pre-treatment drug resistance transmission chains

Abstract

In Brazil, the transmission of HIV drug resistance strains has increased from 6.6 per cent in 2001 to 9.5 per cent in 2015. Besides being associated with virological failure in first-line antiretroviral therapy, drug resistance can also compromise pre-exposure prophylaxis, mother-to-child transmission prevention, and post-exposure prophylaxis. In order to monitor HIV primary resistance in Brazil, we aimed to identify pre-treatment drug resistance transmission chains in both national and regional levels. Sampling strategy was based on the HIV Threshold Survey methodology (HIV-THS, WHO). Subjects were selected from fifty-one highly populated cities present in all five Brazilian macro-regions. HIV pol subtype was determined by Rega HIV Subtyping Tool and maximum likelihood phylogenetics. The presence of pre-treatment drug resistance transmission clades was verified by maximum likelihood tree (PhyML 3.0) for subtypes B, C, and F, separately, in both national and regional levels. Phylogenetic trees were edited using FigTree v1.4.3. We analyzed 1,566 HIV pol sequences from antiretroviral naïve individuals with recent HIV infection. The presence of surveillance drug resistance mutations (SDRM) was previously characterized by Stanford HIVdb Program, with a nationwide prevalence of 9.5 per cent. Overall, subtype B (66 per cent) was the most prevalent, followed by subtypes C (13 per cent), F (11 per cent) and recombinant forms (10 per cent). Subtypes A, D, and CRF 02-AG were identified in<1 per cent. The distribution of HIV subtypes was slightly different among the different geographic regions, especially in the South, where subtype C represented 51 per cent of analyzed sequences. Sequences presenting SDRM appeared dispersed on all phylogenetic trees, showing no specific pre-treatment drug resistance transmission clade, when considering both the national level or the five Brazilian geographic regions, separately. The HIV subtype distribution is in accordance with previous reports, emphasizing the high prevalence of subtype C in the Southeast Brazil and the introduction of CRF 02-AG in the Northeast. Phylogenetic analyses showed no specific SDRM transmission clade. Hence, HIV SDRM transmission in Brazil does not seem to occur in a particular population group or geographic region. These results further illustrate the important contribution of phylogenetic studies in predicting future trends in SDRM transmission.