Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India

Abstract

This study was conducted to examine the relationship between adherence, viral load (VL) and resistance among outpatients receiving highly active antiretroviral therapy (HAART) in Bangalore, India. In total, 552 outpatients were recruited and VL testing was conducted for all study participants. HIV-1 genotypic resistance testing was performed for 92 participants with a VL ≥ 1000 copies/ml. Interpretation of resistance mutations was performed according to the Stanford database. Past-month adherence and treatment interruptions for >48 h were assessed via selfreport. At baseline, 34 participants (6%) reported <95% past-month adherence and 110 (20%) reported a history of >48 h treatment interruptions. Combining the two adherence measures, 22% of participants were classified as 'suboptimally adherent'. In total, 24% of study participants (n = 132) had a detectable VL. Among the 92 samples sent for resistance testing, 68% had at least one nucleoside reverse transcriptase inhibitor (NRTI) mutation, with M184V being the most common © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. * Corresponding author. Tel.: +1 415 597 9160; fax: +1 415 597 9213. mekstrand@gmail.com; maria.ekstrand@ucsf.edu (M. Ekstrand). . Authors' contributions: MLE, GS and SC designed the study protocol; VM, SS and NK conducted the viral genotyping at YRGCARE, and in collaboration with AS and RS interpreted its results; RS supervised all laboratory procedures at St John's Research Institute; EH conducted all statistical analyses; MLE drafted the manuscript, with assistance from NK, AS, SS and VM. All authors read, provided feedback on and approved the final manuscript. MLE is guarantor of the paper.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of interest: None declared.Ethical approval: The study received ethical clearance from the University of California, San Francisco (UCSF) Committee on Human Research (CA, USA), the St John's Institutional Ethical Review Board (Bangalore, India) and the Indian Committee on Medical Research. (62%) and with 48% having thymidine analogue mutations. Moreover, 72% had at least one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation and 23% had three or more NNRTI mutations. Both adherence measures were significantly associated with VL (P < 0.001). Suboptimal adherence was significantly associated with resistance mutations (P < 0.02). The findings illustrate for the first time the strong association between suboptimal adherence, treatment failure and drug resistance to first-line HAART in India...

Selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in HIV-1 subtype C: evidence of etravirine cross-resistance

“…Similar trends have been observed in patients with CRF01_AE strains from Thailand (50% Y181C/I/V and 18.7% K101E/H/P) [24] and UK (17% Y181C in those failing efavirenz and 40.5% Y181C were in those failing nevirapine) [25], thus lending credence to the conclusion that Y181C is particularly selected during prolonged exposure to a failing nevirapine-containing regimen [11]. …”

“…Among a total of 552 participants participating in a 2-year longitudinal cohort study [10], 18% (n=101) with detectable viremia were assessed for presence of drug resistance-associated mutations during their baseline visit [11]. Drug resistance genotyping was successfully done from 92 plasma samples from failing patients (viral load >1000 copies/ml) using a validated in-house method [12].…”

Antiretroviral therapy adherence measurement in non-clinical settings in South India

“…The Adult AIDS Clinical Trials Group scale (AACTG) (Chesney et al, 2000) and a single-item visual analog scale (VAS) (Amico et al, 2006) have both been used in India (Ekstrand, Chandy, Heylen, Steward, & Singh, 2010; Ekstrand et al, 2011; McMahon et al, 2013; Shah et al, 2007; Venkatesh et al, 2010; Walshe et al, 2010) and two studies have compared the measures with each other (Ekstrand et al, 2010; McMahon et al, 2013). However, both were conducted in private hospitals and may not be generalizable to non-clinical settings.…”

Effect of mobile telephone reminders on treatment outcome in HIV: evidence from a randomised controlled trial in India

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