Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities.
BACKGROUND
Development of drug-resistance mutations is the main cause of failure in antiretroviral therapy. In Brazil, there is scarce information on resistance pattern for patients failing antiretroviral therapy.


OBJECTIVE
To define the HIV mutational profile associated with drug resistance in Brazilian patients from 5 large cities, after first, second or further failures to antiretroviral therapy.


METHODS
We reviewed genotyping results of 1520 patients failing therapy in five Brazilian cities. Frequency of mutations, mean number of active drugs, viral susceptibility to each antiretrovirals drug, and regional differences were assessed.


RESULTS
Mean time of antiretrovirals use was 22.7±41.1 months. Mean pre-genotyping viral load was 4.2±0.8log (2.1±2.0 after switching antiretrovirals). Mean number of remaining active drugs was 9.4, 9.0, and 7.9 after 1st, 2nd, and 3rd failure, respectively. We detected regional variations in drug susceptibility: while BA and RS showed the highest (∼40%) resistance level to ATV/r, FPV/r and LPV/r, in the remaining cities it was around half of this rate. We detected 90% efavirenz/nevirapine resistance in SP, only 45% in RS, and levels between 25% and 30% in the other cities. Regarding NRTI, we found a similar pattern, with RJ presenting the highest, and CE the lowest susceptibility rates for all NRTI. Zidovudine resistance was detected in only 3% of patients in RJ, against 45-65% in the other cities. RJ and RS showed 3% resistance to tenofovir, while in CE it reached 55%. DRV/r (89-97%) and etravirine (61-85%) were the most active drugs, but again, with a wide variation across cities.


CONCLUSIONS
The resistance mutational profile of Brazilian patients failing antiretroviral therapy is quite variable, depending on the city where patients were tested. This variation likely reflects distinctive choice of antiretrovirals drugs to initiate therapy, adherence to specific drugs, or circulating HIV-1 strains. Overall, etravirine and DRV/r remain as the most active drugs.
Fundação Bahiana de Infectologia (FBaI), Salvador, BA, Brazil; Universidade Federal da Bahia (UFBA), Laboratório de Pesquisa em Infectologia (LAPI), Salvador, BA, Brazil. Electronic address: crbrites@gmail.com.
Carlos
C
Brites
Escola de Ciências da Saúde da Santa Casa de Vitoria, Vitória, ES, Brazil.
Lauro
L
Pinto-Neto
Unichristus, Fortaleza, CE, Brazil.
Melissa
M
Medeiros
Fundação Oswaldo Cruz (FIOCRUZ), Instituto de Infectologia Evandro Chagas, Rio de Janeiro, RJ, Brazil.
Estevão
E
Nunes
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Eduardo
E
Sprinz
Universidade de Campinas (UNICAMP), Campinas, SP, Brazil.
Mariana
M
Carvalho
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors
Brazil; HIV; Mutations; Resistance