Antiretroviral (ARV) drug resistance in the developing world


To describe the overall prevalence of ARV resistance in the developing world, focusing on: (1) treatment naïve populations, (2) the resistance consequences of prevention of mother to child transmission (pMTCT) drug regimens, and (3) the relationship of medication adherence to resistance.
We searched PubMed(R), EMBASE, the Cochrane Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness (DARE). Additional sources of evidence included the Stanford University HIV Drug Resistance Database; reports of WATCH: Worldwide Analysis of Resistance Transmission over Time of Chronically and Acute Infected HIV-1 infected persons; a recent unpublished pMTCT overview; and various conference proceedings. Studies that did not report original research, that reported data already reported in another article, and case studies of fewer than 20 individuals were excluded. Of 1,122 titles identified, 117 journal articles and presentations were included.
We abstracted data on geographic region, number of participants, subject demographics, HIV viral clade, medications taken (if any), years of data collection, how people were selected for resistance testing, and how and when resistance was assessed. Because of study heterogeneity, pooling was not possible; thus, the data are summarized qualitatively. Differences by region, population group, and HIV viral clade are described.
The patterns of ARV resistance among treatment naïve populations worldwide appear to reflect geographic trends in use of ARV medications. A worldwide surveillance program (WATCH) found the rate of resistance (to any drug) among treatment naïve individuals was 5.5 percent in Africa, 7.4 percent in East Asia, 5.7 percent in Southeast Asia, and 6.4 percent in Latin America, lower than in North America (11.4 percent) and Europe (10.6 percent). Resistance data on HIV clades other than A, B, C, and D were too scarce to permit reliable conclusions. We also identified very few studies designed to assess the effect of health services delivery factors or medication adherence on the development of resistance in patients in developing countries. Evidence provided by longitudinal analyses suggests that, among women taking intrapartum single dose nevirapine (SD-NVP) to prevent mother-to-child transmission of HIV, both the overall prevalence of NNRTI resistance as well as the frequency of mutant virus in the overall viral population decreases with time since SD-NVP prophylaxis was received.
In future resistance studies, rare HIV clades should be over-sampled in order to provide statistically meaningful data. Resistance surveillance programs should be maintained throughout the developing world, and data should be reported and analyzed in a consistent and timely manner. Where resources permit, studies of adherence in developing regions should conduct resistance testing.

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    • "Finally, pretreatment HIV genotyping is not routinely used in poor countries. This could lead to lower efficacy in case of primary resistance, particularly in countries where nevirapine monotherapy is generally used to prevent mother-to-child transmission [25]. Of note, we found no association between the class of cART (in particular PI vs. NNRTI) and genital viral shedding. "
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    ABSTRACT: To assess the impact of long-term combined antiretroviral therapy (cART) on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL); to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission. Women with undetectable PVL (<50 copies/mL) for >6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL). Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated. Eighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%). There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08). In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2-61) and current residual viremia (20<PVL<50 cp/mL) (OR = 3.4; 95%CI = 1.1-10.9). Neither the classes of cART regimen nor the presence of genital bacterial or fungal colonization were associated with HIV-DNA detection in CVL. Twenty-eight percent of the women had unprotected intercourse with their regular HIV-seronegative male partner, for between 8 and 158 months. None of their male partners became infected, after a total of 14 000 exposures. In our experience, HIV-RNA was undetectable in the genital tract of women with sustained control of PVL on cART. HIV-DNA shedding persisted in about one third of cases, with no substantial evidence of residual infectiousness.
    PLoS ONE 08/2013; 8(8):e69686. DOI:10.1371/journal.pone.0069686 · 3.23 Impact Factor
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    • "In this cohort, nevirapine had the highest prevalence of drug-associated mutations. The drug has a long half-life, a simple mutational pathway and is prone to rapid resistance even with the single doses used in PMTCT (Grossman, et al. 2004, Jourdain, et al. 2004, Shekelle, et al. 2007). Unfortunately, despite contacting or visiting the referring clinics, the demographic details to determine the extent of this effect were not available for this analysis because of loss of follow-up for most of the affected patients. "

    HIV Testing, 01/2012; , ISBN: 978-953-307-871-7
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    • "Lack of adherence to antiretroviral (ARV) medications is one of the key challenges for HIV care and treatment programmes [1-3]. While strict adherence promotes viral suppression, poor adherence results in further immunosuppression and resistance to antiretroviral medications [4,5]. Adherence is especially challenging among young infants and children, and supervising daily child dosing requires organizational skills, age-appropriate negotiation skills, and an understanding of how to actually draw up and administer medication to a potentially uncooperative child. "
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    ABSTRACT: Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family/friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes.
    Journal of the International AIDS Society 12/2010; 13(1):48. DOI:10.1186/1758-2652-13-48 · 5.09 Impact Factor
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