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Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays.

ABSTRACT: HIV-1 genotyping for antiretroviral drug resistance mutations (DRMs) were developed based basically on subtype B HIV-1 Group M, which represents only 10% of HIV strains worldwide. In sub-Saharan Africa, non-B subtypes HIV-1 largely predominate and HIV-1 genetic diversity could affect the performance of drug resistance genotyping assays. We compared prospectively the performance of the ViroSeq(®) and Trugene(®) genotyping assays to detect DRM in HIV-1-infected adult patients living in Douala, Cameroun.DRM in protease (P) and reverse transcriptase (RT) genes were assessed in parallel using both ViroSeq(®) and Trugene(®) assays in plasma samples from 45 first-line antiretroviral treatment-experienced patients in Douala, Cameroon.Trugene HIV-1 Genotyping Assay(®) (Siemens Health Care Diagnostics, NY, USA) and ViroSeq HIV-1 Genotyping System(®)(Celera Diagnostics, CA, USA) assessed equivalently antiretroviral DRMs in P and RT genes from non-B HIV-1 Group M in 44 Cameroonian adults in virological failure; Trugene(®) was slightly more sensitive than ViroSeq(®) (100% vs. 91%). One patient infected by HIV-1 Group N was successfully amplified only by the Trugene HIV-1 Genotyping assay(®), while ViroSeq HIV-1 Genotyping System v2.0(®) assay could not.Results showed the higher performance of the Trugene(®) system to detected and amplify P and RT genes targeting DRM to the principal antiretroviral drugs used in sub-Saharan Africa. Discrepancies between the results of HIV viral load assays and molecular tests should alert clinicians and virologists to the possibility of infection by an atypical variant virus, especially in Central Africa where very broad HIV-1 genetic diversity exists.

SUBMITTER: Jenabian MA

PROVIDER: S-EPMC4743293 | biostudies-literature | 2015 Nov-Dec

REPOSITORIES: biostudies-literature

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Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays.

Jenabian Mohammad-Ali MA Talla Frédéric F Talla Perrine P Mbopi-Kéou François-Xavier FX Charpentier Charlotte C Kane Coumba Toure CT Bélec Laurent L

Nigerian medical journal : journal of the Nigeria Medical Association 20151101 6

<h4>Background</h4>HIV-1 genotyping for antiretroviral drug resistance mutations (DRMs) were developed based basically on subtype B HIV-1 Group M, which represents only 10% of HIV strains worldwide. In sub-Saharan Africa, non-B subtypes HIV-1 largely predominate and HIV-1 genetic diversity could affect the performance of drug resistance genotyping assays. We compared prospectively the performance of the ViroSeq(®) and Trugene(®) genotyping assays to detect DRM in HIV-1-infected adult patients li ...[more]

PMID: 26903701

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Project description:IntroductionThe current expansion of antiretroviral treatment (ART) in the developing world without routine virological monitoring still raises concerns on the outcome of the strategy in terms of virological success and drug resistance burden. We assessed the virological outcome and drug resistance mutations in patients with 36 months' ART experience, and monitored according to the WHO public health approach in Cameroon.MethodsWe consecutively recruited between 2008 and 2009 patients attending a national reference clinic in Yaoundé - Cameroon, for their routine medical visits at month 36±2. Observance data and treatment histories were extracted from medical records. Blood samples were collected for viral load (VL) testing and genotyping of drug resistance when HIV-1 RNA ≥1000 copies/ml.ResultsOverall, 376 HIV-1 infected adults were recruited during the study period. All, but four who received PMTCT, were ART-naïve at treatment initiation, and 371/376 (98.7%) started on a first-line regimen that included 3TC +d4T/AZT+NVP/EFV. Sixty-six (17.6%) patients experienced virological failure (VL ≥1000 copies/ml) and 53 carried a resistant virus, thus representing 81.5% (53/65) of the patients who failed. Forty-two out of 53 were resistant to nucleoside and non-nucleoside reverse-transcriptase inhibitors (NRTIs+NNRTIs), one to protease inhibitors (PI) and NNRTIs, two to NRTIs only and eight to NNRTIs only. Among patients with NRTI resistance, 18/44 (40.9%) carried Thymidine Analog Mutations (TAMs), and 13/44 (29.5%) accumulated at least three NRTI resistance mutations. Observed NNRTI resistance mutations affected drugs of the regimen, essentially nevirapine and efavirenz, but several patients (10/51, 19.6%) accumulated mutations that may have compromised etravirine use.ConclusionsWe observed a moderate level of virological failure after 36 months of treatment, but a high proportion of patients who failed developed drug resistance. Although we found that for the majority of patients, second-line regimens recommended in Cameroon would be still effective, accumulated resistance mutations are of concern and may compromise future treatment strategies, stressing the need for virological monitoring in resource-limited settings.

Dataset Information

Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays.

Publications

Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays.

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