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

Abstract

Antiretroviral therapy (ART) has reduced morbidity and mortality related to human immunodeficiency virus (HIV) infection, but in spite of this advance, HIV mutations decrease antiretroviral susceptibility, thus contributing to treatment failure in patients. Genotyping HIV-1 allows the selection of new drugs after initial drug failure. This study evaluated the genotypic profi le of HIV-1 isolates from treated (drug-experienced) patients in Paraná, Brazil. The prevalence of mutations in reverse transcriptase (RT) and protease (PR) genes were assessed. We analyzed 467 genotypes of patients with HIV-1 viral loads above 1,000 copies/mL. Mutations at HIV-1 RT and PR genes and previously used ART regimens were recorded. The most prevalent RT mutations were: 184V (68.31%), 215YF (51.6%), 103NS (46%), 41L (39.4%), 67N (38.54%), 210W (23.5%), 190ASE (23.2%), and 181C (17.4%). PR mutations were 90M (33.33%), 82ATFS (29%), 46I (26.8%) and 54V (22.2%). The prevalence of mutations was in line with previous national and international reports, except to nonnucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specifi c drugs, leading to treatment failure in HIV patients.

Discordance between genotypic resistance and pseudovirus phenotypic resistance in AIDS patients after long‐term antiretroviral therapy and virological failure

“…We have found that reverse transcriptase (RT) resistance‐associated mutation rate was 100% (27/27) (data not shown). This rate is higher than the 86.7% found by Brazilian authors , and is also significantly higher than those reported in short‐term treatment studies (32.4–70.5%) conducted in China . Resistance may be assessed either by genotype or phenotype‐based assays.…”

“…Studies in South Africa, Uganda, and Brazil found that drug resistance mutation rates in patients experiencing HAART and virological failure were over 86%. Beyond that drug resistance mutation sites continued to increase after long‐term HAART and treatment failure . The pilot study for the National Free ART Program in China started 2002 .…”

Drug Resistance Mutations in HIV Type 1 Isolates from Patients Failing Antiretroviral Therapy in Morocco

“…These prevalences were different from those reported in other series where M46L, V82A, and L90M occurred, respectively, in 21-25%, in 19-23%, and in 26-37% of patients. 12,24,26 We found that the prevalence of mutations related to NRTIs and PIs increased yearly with exposure to drugs of the same class. For NNRTIs a high level of mutation was observed within 1 year of treatment failure.…”

“…21,22 The mutation M184V was the predominant mutation in this sample and its prevalence (70%) was comparable with that described for HIV patients failing HAART in other settings. [23][24][25] This can likely be attributed to the wide use of 3TC in Morocco. The M184I was observed in two patients infected with a subtype B who had recently initiated therapy with 3TC.…”

Patterns of HIV-1 Drug-Resistance Mutations among Patients Failing First-Line Antiretroviral Treatment in South India

“…However, the most frequent mutations in RT were associated with ZDV and NNRTI exposure, which confirms the low genetic barrier of these drugs. 22 Studies have shown that non-subtype B viruses might be more prone to rapid emergence of NNRTI resistance because of background polymorphisms in the RT gene. 23 After NVP use, Y181C is the most frequent mutation in the HIV-1 RT gene, but this does not confer high-level cross-resistance to EFV.…”