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Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco.

ABSTRACT: The emergence of viral-resistant strains is a major problem for the medical management of HIV-infected individuals. The aim of this study was to characterize viral subtypes and drug-resistance mutations (DRMs) in HIV-1 isolates from patients failing antiretroviral therapy (ART). A total of 45 HIV-1-infected patients failing ART were enrolled. The viral RT and Prot genes were amplified and sequenced to determine subtypes and potential DRMs. The subtype distribution was 74% subtype B, 11% subtype A, 9% CRF02-AG, 4% subtype G, and 2% subtype C. Virus samples from 34% of the patients had no DRM while 53%, 27%, and 2% of samples carried at least one DRM conferring resistance to drugs of one, two, or three classes, respectively. DRMs were observed in 50% of the patients infected with non-B strains. The prevalence of nucleoside transcriptase inhibitor (NRTI) mutations was 48%, M184V being largely predominant. The prevalence of nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations was 13%, with K103N present in 57% of samples from NNRTIs-exposed patients. The prevalence of protease inhibitor (PI) mutations was 22%, with major mutations V82A and M46I seen in 16% and 11% of viruses from PI-exposed individuals, respectively. Our study shows the emergence of DRMs in HIV-1 isolates from Moroccan patients failing ART. Although not surprising, the data plead for longitudinal surveys of the dynamics of emergence of DRMs (with a focus on multidrug resistance) in treated patients and circulation of resistant HIV-1 strains in this country.

SUBMITTER: El Annaz H

PROVIDER: S-EPMC3399567 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco.

El Annaz Hicham H Recordon-Pinson Patricia P Tagajdid Rida R Doblali Toufik T Belefquih Bouchra B Oumakhir Siham S Sedrati Omar O Mrani Saad S Fleury Hervé H

AIDS research and human retroviruses 20111123 8

The emergence of viral-resistant strains is a major problem for the medical management of HIV-infected individuals. The aim of this study was to characterize viral subtypes and drug-resistance mutations (DRMs) in HIV-1 isolates from patients failing antiretroviral therapy (ART). A total of 45 HIV-1-infected patients failing ART were enrolled. The viral RT and Prot genes were amplified and sequenced to determine subtypes and potential DRMs. The subtype distribution was 74% subtype B, 11% subtype ...[more]

PMID: 21919803

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Project description:ObjectiveLimited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.MethodsData from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.ResultsThe study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033).ConclusionMajor protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

Dataset Information

Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco.

Publications

Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco.

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