Transmitted Drug Resistance and Antiretroviral Treatment Outcomes in Non-Subtype B HIV-1–Infected Patients in South East Asia

JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 01/2014; 66(1). DOI: 10.1097/QAI.0000000000000108
Source: PubMed


We compared treatment outcomes of transmitted drug resistance (TDR) in patients on fully or partially sensitive drug regimens.
Factors associated with survival and failure were analyzed using Cox proportional hazards and discrete time conditional logistic models.
TDR, found in 60/1471 (4.1%) Asian treatment naïve patients, was one of the significant predictors of failure. Patients with TDR to >1 drug in their regimen were >3 times as likely to fail compared to no TDR.
TDR was associated with failure in the context of non-fully sensitive regimens. Efforts are needed to incorporate resistance testing into national treatment programs.

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    ABSTRACT: Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow-up time started from ART initiation and was censored at 24 months, loss to follow-up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social desirability bias could not be excluded, a greater emphasis on more frequent adherence counselling immediately following ART initiation and through the first six months may be valuable in promoting treatment and programme retention.
    Full-text · Article · May 2014 · Journal of the International AIDS Society
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    ABSTRACT: Objectives: The objective of this study was to determine the prevalence and correlates of pretreatment drug resistance (PDR) to first-line antiretroviral drugs among people initiating therapy for HIV in Vietnam. Methods: Blood was collected during November 2009 to October 2010 from people consecutively initiating ART in four purposively selected public outpatient clinics in three Vietnamese cities. At each study site, recruitment lasted for 6-10 months until the target sample size (range 120-130 individuals) had been reached. The viral load was measured in 501 samples; 490 samples (viral load ≥1000 copies/mL) were genotyped using a nucleotide population-based sequencing assay. Self-reported demographic and clinical data were elicited through interviews. We classified drug-resistance-associated mutations (DRMs) according to the 2009 WHO surveillance list. Results: DRMs were identified in 17/490 participants (3.5%; 95% CI 2.2%-5.5%). The prevalence of DRMs was 1.6% (8/490) against NRTIs, 1.6% (8/490) against NNRTIs and 0.8% (4/490) against PIs; three (0.6%) participants were resistant to both NRTIs and NNRTIs. The overall prevalence of PDR to first-line drugs was low [2.7% (13/490); 95% CI 1.6%-4.4%]. The prevalence of PDR to first-line drugs was greater among 198 HIV-infected participants who injected drugs than among 286 participants who reported risks for sexually acquired HIV (4.0% versus 1.4%, P = 0.079). Multivariable logistic regression analysis suggested that PDR to first-line drugs was significantly higher among people who injected drugs (OR = 3.94; 95% CI 1.13-13.68). Conclusions: With low PDR, first-line ART may be effective in Vietnam and pretreatment genotyping may be unnecessary. Continuing strategies for the prevention and surveillance of antiretroviral resistance are important for maintaining a low prevalence of antiretroviral resistance in Vietnam. The association between resistance and injection drug use warrants further research.
    Full-text · Article · Nov 2014 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries. We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups. A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM. TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.
    Full-text · Article · Nov 2014 · AIDS (London, England)
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