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Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India.

ABSTRACT: Objective. The increased use of antiretroviral therapy (ART) has reduced the morbidity and mortality associated with HIV, adversely leading to the emergence of HIV drug resistance (HIVDR). In this study we aim to evaluate the prevalence of HIVDR mutations in ART-naive HIV-1 infected patients from northern India. Design. Analysis was performed using Viroseq genotyping system based on sequencing of entire protease and two-thirds of the Reverse Transcriptase (RT) region of pol gene. Results. Seventy three chronic HIV-1 infected ART naïve patients eligible for first line ART were enrolled from April 2006 to August 2008. In 68 patients DNA was successfully amplified and sequencing was done. 97% of HIV-1 strains belonged to subtype C, and one each to subtype A1 and subtype B. The overall prevalence of primary DRMs was 2.9% [2/68, 95% confidence interval (CI), 0.3%-10.2%]. One patient had a major RT mutation M184V, known to confer resistance to lamivudine, and another had a major protease inhibitor (PI) mutation D30N that imparts resistance to nelfinavir. Conclusion. Our study shows that primary HIVDR mutations have a prevalence of 2.9% among ART-naive chronic HIV-1 infected individuals.

SUBMITTER: Sinha S

PROVIDER: S-EPMC3312221 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naïve Population from Northern India.

Sinha S S Ahmad H H Shekhar R C RC Kumar N N Dar L L Samantaray J C JC Sharma S K SK Bhargava A A Pandey R M RM Mitsuyasu R L RL Fahey J L JL

AIDS research and treatment 20120315

Objective. The increased use of antiretroviral therapy (ART) has reduced the morbidity and mortality associated with HIV, adversely leading to the emergence of HIV drug resistance (HIVDR). In this study we aim to evaluate the prevalence of HIVDR mutations in ART-naive HIV-1 infected patients from northern India. Design. Analysis was performed using Viroseq genotyping system based on sequencing of entire protease and two-thirds of the Reverse Transcriptase (RT) region of pol gene. Results. Sevent ...[more]

PMID: 22496972

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Project description:BACKGROUND: Access to antiretroviral drugs for HIV-1 infection has increased in sub-Saharan Africa (SSA) during the past few years. Mutations in the HIV-1 genome are often associated with treatment failure as indicated by viral replication and elevated levels of virus in the blood. Mutations conferring resistance to antiretroviral drugs are based on comparing gene sequences with corresponding consensus sequences of HIV-1 subtype B that represents only 10% of the AIDS pandemic. The HIV pandemic in SSA is characterized by high viral genetic diversity. Before antiretroviral drugs become more widely available, it is important to characterize baseline naturally occurring genetic mutations and polymorphisms associated with antiretroviral drug resistance among circulating HIV-1 subtypes. METHODS: The prevalence of mutations associated with antiretroviral drug resistance in protease (PR) and reverse transcriptase (RT) regions among antiretroviral treatment-naïve HIV-1 infected pregnant women was investigated in Bukoba (Kagera) and Moshi (Kilimanjaro) municipalities, Tanzania, between September and December 2005. The HIV-1 pol gene was amplified using primers recognizing conserved viral sequences and sequenced employing BigDye chemistry from 100 HIV-1 seropositive treatment-naïve pregnant women and 61 HIV-1 seropositive women who had received a single dose of Nevirapine (sdNVP). Positions 1-350 of the RT and 1-99 of the PR genes were analyzed for mutations based on the Stanford University HIV Drug Resistance Database. RESULTS: HIV-1 subtypes A, C, D, CRF10_CD and Unique Recombinant Forms (URF) were detected. Primary mutations associated with NRTI and NNRTI resistance were detected among 3% and 4% of treatment-naïve strains, respectively. Primary mutations associated with NRTI and NNRTI resistance were detected in 1.6% and 11.5% of women who had received sdNVP, respectively. None of the primary mutations associated with PI resistance was found. Polymorphisms detected in RT and PR sequences were mainly mutations that are found in the consensus sequences of non-B subtypes CONCLUSION: Based on the WHO HIV Drug Resistance Research Network Threshold of less than 5%, the baseline prevalence of primary mutations among treatment-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions was low. The significance of HIV-1 subtype B polymorphic positions with respect to antiretroviral resistance identified among the prevalent HIV-1 subtypes is unknown. More studies addressing the correlation between polymorphic mutations, antiretroviral resistance and clinical outcome are warranted in regions where non-B subtypes are prevalent.

Project description:ObjectiveDescribe trends in antiretroviral treatments and drug resistance mutations among Swedish HIV-patients over time 1997-2011.MethodsTreatment histories, viral sequences, and demographic and clinical data were retrieved from the national database InfCareHIV. All ART-experienced patients were included (N?=?6537), while resistance tests were restricted to those obtained ?90 days after ART start. This cohort is fully representative for Sweden since the database covers virtually all diagnosed HIV-patients since the start of the epidemic. Patients were grouped according to the year of first ART, and treatments and mutations were analyzed by calendar year.ResultsThe prevalence of major drug resistance mutations decreased dramatically over time, most rapidly between 2003 and 2007. Since then there has been a continued slow decrease for NRTI- and PI-associated mutations with an overall prevalence among all ART-experienced patients at 1.1% (NRTI) and 0.3% (PI) in 2011. NNRTI resistance reached the lowest level in 2007-2009 (0.6%), but is now increasing (0.9% in 2011). Patients with first ART exposure before 2001 are still highly overrepresented among those with PI and, to a lesser extent, NRTI resistance. In contrast, almost half of the patients with NNRTI mutations in 2011 initiated their first ART after 2007.ConclusionsTremendous improvements in ART options and knowledge have resulted in rapidly declining levels of resistance, and most of the current NRTI and PI mutations are found among patients with a history of suboptimal treatments. However, NNRTI resistance is increasing and is primarily found in patients infected in low- and middle-income countries who initiated ART in recent years. It is plausible that these patients were infected with resistant strains and it is therefore suggested that resource-rich countries like Sweden should test for resistance in minor quasispecies or use PI-based first-line regimens in patients who are at increased risk of carrying resistant virus.

Dataset Information

Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India.

Publications

Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naïve Population from Northern India.

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