HIV-1 antiretroviral drug resistance mutations in subtype B, F, and recombinants B/F in Santos, Brazil were characterized. We studied 83 samples from individuals enrolled at the Brazilian HIV/AIDS programs from Santos. These patients have been treated with multiantiretroviral therapy. Samples were collected in 2006; RNA was extracted from plasma and used as a target to amplify the pol gene of HIV-1. PCR products were sequenced on both strands, phylogenetic analyses were performed by neighbor-joining, and recombination was evaluated by bootscan. pol gene sequencing of the samples revealed that 54 strains belonged to subtype B, 4 were subtype F, 1 was subtype C, and 24 were B/F recombinants. Recombinant break points in 20 samples are the same identified in CRF28_BF and CRF29_BF. Drug resistance mutations identified in common to subtypes B, F, and recombinants B/F were protease inhibitors M46I/L (29%), I54V (24%), A71V (22%), and V82A/F (31%); reverse transcriptase nucleoside resistance mutations M41L (52%), D67N (30%), K70R (26%), M184V (88%), L210W (29%), T215Y/I/F (65%), and K219Q/E/N (28%); and reverse transcriptase nonnucleoside resistance mutation K103N (52%). Our results suggest that, in general, the same amino acids are emerging in both subtypes B, F, and recombinant forms BF due to the selective pressure of antiretrovirals. Recombinant break points in samples are the same as identified in CRF28_BF and CRF29_BF and are recognized as important for the evolution of the local epidemic.
Santos is a Brazilian port city with high HIV incidence, high primary antiretroviral resistance levels, high HIV-1 BF recombinants prevalence, and high rates of antiretroviral virologic failure. We evaluated factors related to virologic failure after 48 weeks of HAART in this population. We compared demographic and HIV profiles among 43 individuals with virologic failure (group 1) and 37 with virologic success (group 2) after 48 weeks of HAART initiation. The overall primary antiretroviral resistance prevalence was 31.2%; 46.5% in group 1 and 13.5% in group 2 (p < 0.005). Nine patients from group 1 and seven from group 2 were infected by F or BF strains. Fifteen individuals presented with NRTI mutations, 13 with NNRTI mutations, three with PI mutations, and five with NRTI and NNRTI mutations. No significant differences were observed in baseline viral load, CD4, clade assignment, antiretrovirals used, or demographics among groups or patients harboring resistant versus wild-type viruses. In this region, there was a high prevalence of antiretroviral resistance among long standing infected patients whose disease had progressed. This finding supports the concept that resistance testing prior to ART initiation is cost effective. The association between primary antiretroviral resistance and virologic failure may suggest that primary resistance greatly impairs antiretroviral activity.
HIV-1 from infected subjects has been characterized in order to provide a more accurate view of the strains that are currently found in a given region. In this report, we focused on characterizing the pol gene diversity obtained from newly diagnosed patients in Santos metropolitan area, Brazil. This region is composed of nine cities and an international port. Analysis of the 33 samples revealed that 22 strains belonged to subtype B, 4 to subtype F, and 2 to subtype C; 5 strains were B/F recombinants. Our results demonstrated that 18.2% of samples were primary antiretroviral resistance genotypic mutations, with high-level resistance to reverse transcriptase inhibitors in both subtypes B and F and in recombinant forms B/F. Our data revealed that the primary antiretroviral resistance genotypic mutations should be carefully investigated in developing countries with widespread access to antiretrovirals, such as Brazil.
Genotypic resistance is currently assessed through direct sequencing, which cannot detect resistant strains below 20%. We compared the genotypic resistance profile of virions and proviruses using population-based analysis and single genome sequencing of the protease region of the pol gene in samples collected from five individuals in whom indinavir monotherapy resulted in treatment failure. Single genome sequencing showed that not all strains present the same resistance mutations, which can be dispersed across different HIV genomes. The resistance profile found in plasma was very similar to that found in peripheral blood mononuclear cells (PBMCs), confirming the utility of assessing proviral DNA as for a means of determining antiretroviral resistance.
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