Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil

Abstract

Genotype testing for HIV-1 drug resistance is useful for selecting antiretroviral drug regimens for patients experiencing therapeutic failure, but the optimal means for interpreting the test results is unknown because many HIV-1 protease and reverse transcriptase (RT) mutations contribute to drug resistance. This study identified common combinations of resistance mutations related to antiretroviral resistance profiles. From April 2002 to March 2004, 101 protease and RT sequences were determined for HIV-1 isolates from patients who were failing antiretroviral therapy. The resistance profile was evaluated using the Stanford Database program. Male patients predominated (76.2%), the median age was 38 years, the average CD4 count was 279.21 cells/mm(3) and the average viral load was 4.49 log. In relation to protease inhibitors (IP) 31 mutation patterns were detected, 49 mutation patterns were detected in Nucleoside RT Inhibitors (NRTI), and 17 patterns were found in the Non Nucleoside RT Inhibitors (NNRTI). K65R was detected in 5.9% of the isolates. The most frequent mutations were: L90M, M184V and K103N related to PI's, NRTI's and NNRTI's, respectively. The best antiretroviral susceptibility was found to be Lopinavir in the PI class and Tenofovir in the NRTI class. The top six mutation patterns accounted for 49% of the resistance to PI's, for 38.5% of NRTI resistance, and the top two mutation patterns accounted for 40.9% of resistance to NNRTI's.

HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

“…Most of other Brazilian studies reported NNRTI prevalence of mutations of 30 to 55.4%. 21,23,25,26 In Santos, the overall NNRTI prevalence was not explicit, but K103N occurred in 52% of patients, whereas in these data from Paraná it was 43.4%. 27 At Brazilian Northeast region, the specifi c mutations were even higher, with 62% substitutions in codon 103, 38.7% in codon 190 and 181 in codon 29.2%.…”

“…At Brazilian Northeast region this mutation was seen in 3.4% of patients and, specifi cally in the state of Ceará, in 5.9% of cases. 23,26 The overall prevalence of NNRTI mutations (67.7%) was higher than in other Brazilian series, probably because recently described NNRTI mutations (codons 101, 106, 179) were included in the analysis. Most of other Brazilian studies reported NNRTI prevalence of mutations of 30 to 55.4%.…”

“…21,23,25,26 Only one national study showed even higher prevalence of wildtype virus (15.3%). 20 The most prevalent mutation occurred at codon 184 (68.31%), as reported in São Paulo (64%), 24 Rio de Janeiro (67%), 23 and Northeast Brazil (66%).…”

“…20 From 2004 to 2007, many other authors showed data from the prevalence of antiretroviral resistance in adults from Bahia, São Paulo, Rio de Janeiro, Federal District and North Eastern states. [21][22][23][24][25][26][27] The aim of this study is to analyze the genotypic profile of patients tested for resistance in the Brazilian state of Paraná, in order to determine the frequency of RT and PR mutations among patients failing ART.…”

HIV‐1 primary and secondary antiretroviral drug resistance and genetic diversity among pregnant women from central Brazil

“…Recent HIV-1 molecular epidemiology studies from Brazil have shown that recombinant forms, especially from subtypes B and F1, are being generated and transmitted throughout the country away from the epicenter of the epidemics which lies in the southeast region of the country [Cavalcanti et al, 2007;Medeiros et al, 2007;Stefani et al, 2007;Guimarã es et al, 2008]. In a continental country like Brazil, molecular epidemiology studies in distinct populations from different geographic regions are important to map HIV-1 diversity in the country.…”