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Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa.

ABSTRACT: Data on antiretroviral drug resistance among drug-naive persons are important in developing sentinel and surveillance policies. This study was conducted to determine the prevalence of antiretroviral drug resistance mutations among drug-naïve HIV-infected individuals attending a voluntary testing and counselling centre at the Mankweng Hospital in northeastern South Africa. In total, 79 drug-naïve HIV-positive individuals were sequentially recruited during February 2008-December 2008. Drug resistance mutations were determined using the calibrated population resistance tool available on the Stanford HIV drug resistance database. Viral DNA was obtained from 57 (72%) of the 79 individuals. Reliable nucleotide sequences were obtained for 54 reverse transcriptase (RT) and 54 protease (PR) gene regions from 54 individuals. Overall, five sequences (9.3%) harboured drug resistance mutations (95% confidence interval -1.53 to 16.99). Four (7.4%) of these were nucleoside RT inhibitor mutations (D67G, D67E, T69D, and T215Y), and one (1.9%) was a PR inhibitor mutation (M46I). No major non-nucleoside RT resistance mutation was detected. Several minor resistance mutations and polymorphisms common in subtype C viruses were observed in the PR and RT genes. Phlyogenetic analysis of the partial pol sequences showed that 52 (96%) of the 54 isolates were HIV-1 subtype C. One isolate (08MB08ZA) was HIV-1 subtype B while another (08MB26ZA) was related to HIV-1 subtype J. HIV-1 subtype recombination analysis with REGA assigned the pol sequence to HIV subtype J (11_cpx) with a bootstrap value of 75%. The prevalence of drug resistance mutations observed in the population studied was relatively higher than previously reported from other parts of South Africa. In addition, this is apparently the first report of an HIV-1 subtype J-like virus from northeastern South Africa.

SUBMITTER: Nwobegahay JM

PROVIDER: S-EPMC3190360 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naïve persons visiting a voluntary testing and counselling centre in northeastern South Africa.

Nwobegahay Julius M JM Bessong Pascal O PO Masebe Tracy M TM Mavhandu Lufuno G LG Iweriebor Benson C BC Selabe Gloria G

Journal of health, population, and nutrition 20110801 4

Data on antiretroviral drug resistance among drug-naive persons are important in developing sentinel and surveillance policies. This study was conducted to determine the prevalence of antiretroviral drug resistance mutations among drug-naïve HIV-infected individuals attending a voluntary testing and counselling centre at the Mankweng Hospital in northeastern South Africa. In total, 79 drug-naïve HIV-positive individuals were sequentially recruited during February 2008-December 2008. Drug resista ...[more]

PMID: 21957668

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Project description:HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.

Project description:OBJECTIVE:To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. METHODS:Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). RESULTS:Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. CONCLUSION:Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B HIV infection.

Project description:BackgroundAccording to World Health Organization (WHO) guidelines, which have also been adopted by the National AIDS Control Organization (NACO), India, Efavirenz-based Anti-Retroviral Therapy (ART) is better in Human-Immunodeficiency-Virus (HIV)-infected patients who are also being treated with Rifampicin-based Anti-Tuberculous Therapy (ATT). However, Efavirenz is much more expensive. We hypothesize that Nevirapine is a cheaper alternative that possesses equal efficacy as Efavirenz in HIV-Tuberculosis (TB) co-infected patients.MethodsA parallel open-label randomized clinical trial was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi and National AIDS Research Institute (NARI), Pune. Those who were ART-naïve and co-infected with TB were randomized to receive either Nevirapine (Group 1)- or Efavirenz (Group 2)-based ART along with Rifampicin-based ATT. ATT was begun first in ART-naïve patients according to the NACO guidelines, with a median of 27 days between ATT and ART in both groups. The primary endpoint was a composite unfavourable outcome (death and/or ART failure) at 96 weeks, and the secondary outcome was successful TB treatment at 48 weeks.ResultsA total of 284 patients (mean age 36.7 ± 8.1 years) were randomized in a 1:1 ratio to receive either Nevirapine (n = 144)- or Efavirenz (n = 140)-based ART after a median ATT-ART gap of 27 days. The median CD4 count was 105 cells/μl, with a median viral load of 820,200 copies/μl and no significant difference between the groups. Composite unfavourable outcomes were reported in 49 patients in the Nevirapine group and 51 patients in the Efavirenz group (35.3% vs. 36.9%; hazard ratio, 0.95, 95% confidence interval (CI), 0.63,1.43, adjusted). There was no difference in successful TB treatment outcome between the groups (71.5% vs. 65.6%, 95% CI -3.8,17.9, adjusted). The results were similar, showing no difference between the groups in the two centres of the study after adjusting for disease stage.ConclusionsComposite unfavourable outcome in HIV-TB co-infected patients who were ART-naïve showed no statistically significant difference in the Nevirapine or Efavirenz groups.. Therefore, Nevirapine-based ART is a reasonable alternative to Efavirenz in resource-limited settings. However, multi-centric studies with larger sample sizes are required to confirm these findings.Trial registrationNCT01805258 (Retrospectively registered on March 6, 2013) Date of registration: March 2013.

Dataset Information

Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa.

Publications

Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naïve persons visiting a voluntary testing and counselling centre in northeastern South Africa.

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