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Opportunities for sexual transmission of antiretroviral drug resistance among HIV-infected patients in care.

ABSTRACT: To assess opportunities for transmitted drug resistance (TDR), we examined sexual risk behaviours, HIV viraemia and antiretroviral resistance among patients in care.A retrospective, cross-sectional analysis of clinical cohort data.For 244 UNC Center for AIDS Research HIV Clinical Cohort participants, demographic and behavioural data were obtained during in-person interviews between 2000 and 2011. Genotypic resistance tests were interpreted using WHO surveillance drug resistance mutations (SDRMs). Log-linear binomial regression was used to evaluate associations with TDR risk, defined as unprotected sex in the prior 6 months, HIV RNA at least 400 copies/ml and at least one SDRM.Participants included 91 (37%) women and 153 men, of whom 92 (60%) were MSM. Median age was 43 years; 70% were Black (n?=?171). Most (97%) were antiretroviral-experienced; 44% had exposure to more than four regimens. Among 204 individuals on antiretrovirals, 42% reported suboptimal adherence and 29% were viraemic. Over half of participants had at least one SDRM (n?=?131); 26 (11%) had triple-class resistance. Overall, 70% were sexually active, and 55% used condoms inconsistently. Thirty (12%) reported unprotected sex during periods of drug-resistant viraemia. Higher TDR risk was associated with prior homelessness [adjusted prevalence ratio (aPR) 2.20, 95% confidence interval (CI) 1.16-4.18], active substance use (aPR 3.12, 95% CI 1.47-6.62) and nonsignificantly with MSM (aPR 1.75, 95% CI 0.93-3.28).A small but significant proportion of clinic patients with drug-resistant HIV engage in sexual behaviours that place others at risk for TDR. Targeted efforts in secondary prevention could have an impact on TDR incidence, over time.

SUBMITTER: Soeters HM

PROVIDER: S-EPMC3916948 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Opportunities for sexual transmission of antiretroviral drug resistance among HIV-infected patients in care.

Soeters Heidi M HM Napravnik Sonia S Zakharova Oksana M OM Eron Joseph J JJ Hurt Christopher B CB

AIDS (London, England) 20131101 18

<h4>Objective</h4>To assess opportunities for transmitted drug resistance (TDR), we examined sexual risk behaviours, HIV viraemia and antiretroviral resistance among patients in care.<h4>Design</h4>A retrospective, cross-sectional analysis of clinical cohort data.<h4>Methods</h4>For 244 UNC Center for AIDS Research HIV Clinical Cohort participants, demographic and behavioural data were obtained during in-person interviews between 2000 and 2011. Genotypic resistance tests were interpreted using W ...[more]

PMID: 23921618

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Project description:Access to antiretroviral therapy (ART) is increasing in resource-limited settings (RLS) and can successfully reduce HIV-related morbidity and mortality. However, virologic failure and development of viral drug resistance can result in reduced treatment options and disease progression. Additionally, transmission of resistant virus, and particularly multi-drug resistance, could become a public health concern. This study evaluated treatment success and development of ART drug resistance after short-term treatment among patients attending the Comprehensive HIV Care Centre (CCC) of Coast Province General Hospital, Mombasa, Kenya. One hundred and fifty HIV-infected individuals receiving ART were consecutively recruited to participate in the study. After determination of plasma viral load, patients with detectable viral load levels were subjected to genotypic drug resistance testing. At the time of sampling, 132 of the 150 participants were on ART for more than 6 months (median 21 months, IQR = 12-26). An efficient viral load reduction to below 50 copies/ml was observed in 113 (85.6%) of them. Of the 19 patients with a detectable viral load, sequencing of the protease (PR) and reverse transcriptase (RT) gene was successful in 16. Eleven (11) of these 16 patients were infected with a subtype A1 virus. Major PR mutations were absent, but mutations associated with drug resistance in RT were detected in 14 of the 16 patients (87.5%). High-level resistance against at least 2 drugs of the ART regimen was observed in 9/14 (64.3%). The 3TC mutation M184V and the NNRTI mutation K103N were most frequent but also the multi-drug resistance Q151M and the broad NRTI cross-resistance K65R were observed. The results of this study revealed a high rate of treatment success after short term ART in patients treated at a public provincial hospital in a RLS. Nevertheless, the observed high risk of accumulation of resistance mutations among patients failing treatment and the selection of multi-drug resistance mutations in some, remains of great concern for future treatment options and potential transmission to partners.

Project description:BackgroundUpdated World Health Organization guidelines have amplified debate about how resource constraints should impact monitoring strategies for HIV-infected persons on combination antiretroviral therapy (cART). We estimated the incremental benefit and cost effectiveness of alternative monitoring strategies for east Africans with known HIV infection.MethodsUsing a validated HIV computer simulation based on resource-limited data (USAID and AMPATH) and circumstances (east Africa), we compared alternative monitoring strategies for HIV-infected persons newly started on cART. We evaluated clinical, immunologic and virologic monitoring strategies, including combinations and conditional logic (e.g., only perform virologic testing if immunologic testing is positive). We calculated incremental cost-effectiveness ratios (ICER) in units of cost per quality-adjusted life year (QALY), using a societal perspective and a lifetime horizon. Costs were measured in 2008 US dollars, and costs and benefits were discounted at 3%. We compared the ICER of monitoring strategies with those of other resource-constrained decisions, in particular earlier cART initiation (at CD4 counts of 350 cells/mm3 rather than 200 cells/mm3).ResultsMonitoring strategies employing routine CD4 testing without virologic testing never maximized health benefits, regardless of budget or societal willingness to pay for additional health benefits. Monitoring strategies employing virologic testing conditional upon particular CD4 results delivered the most benefit at willingness-to-pay levels similar to the cost of earlier cART initiation (approximately $2600/QALY). Monitoring strategies employing routine virologic testing alone only maximized health benefits at willingness-to-pay levels (> $4400/QALY) that greatly exceeded the ICER of earlier cART initiation.ConclusionsCD4 testing alone never maximized health benefits regardless of resource limitations. Programmes routinely performing virologic testing but deferring cART initiation may increase health benefits by reallocating monitoring resources towards earlier cART initiation.

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Opportunities for sexual transmission of antiretroviral drug resistance among HIV-infected patients in care.

Publications

Opportunities for sexual transmission of antiretroviral drug resistance among HIV-infected patients in care.

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