Dataset Information

Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa.

ABSTRACT: Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy.

SUBMITTER: Ketseoglou I

PROVIDER: S-EPMC3938925 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa.

Ketseoglou Irene I Lukhwareni Azwidowi A Steegen Kim K Carmona Sergio S Stevens Wendy S WS Papathanasopoulos Maria A MA

AIDS research and human retroviruses 20131213 3

Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HI ...[more]

PMID: 24224886

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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.

Project description:INTRODUCTION: The authors report on a health systems strengthening intervention using quality improvement (QI) methods at the subdistrict level to accelerate highly active antiretroviral treatment (HAART) initiation in South Africa. METHODS: Using a phased scale-up design between August 2006 and November 2009, 14 primary healthcare clinics, one community health centre, one district hospital and one tertiary hospital in a subdistrict were recruited into a 'learning network' using QI methods to facilitate cross-facility learning/mentorship/support. Clinic teams consisting of nurses, counsellors, clerks and/or doctors set collective and individual performance targets, analysed their care systems using 'real-time' data feedback, and designed/implemented a set of simple changes to improve HIV testing and HAART initiation rates across the region. DATA ANALYSIS: Primary clinic data were used to measure HAART initiation rates (primary outcome) and HIV testing (secondary outcome). We analysed data variation/trends using an interrupted time series design. Logistic regression analysis was applied to examine trends in HAART initiation during the intervention phases. RESULTS: Clinics in the learning network increased HIV testing by 301.8% from 891/month (SD=94.2) to 3580/month (SD=327.7) (p<0.0001). Monthly HAART initiations increased by 185.5% from 179/month (SD=17.22) to 511/month (SD=44.93) (p<0.0001). During the pilot (phase I), the monthly rate of HAART initiations increased by 3.6 patients. In the prototype collaborative (phase II), there was no acceleration in the rate of increase (3.3/month, p=0.92). Significant acceleration was observed in the rate of increase during the QI scale up (phase III) (10.1/month, p<0.001). The proportion of estimated need for HAART met in the region increased from 35.8% to 72.4% at a time of rapid population growth. CONCLUSION: A QI approach, using learning networks to teach simple data-driven methods for addressing system failures, with increased training and resource inputs, can assist districts to quickly reach universal coverage targets.

Dataset Information

Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa.

Publications

Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa.

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