Evaluation of transmitted HIV drug resistance among recently-infected antenatal clinic attendees in four Central African countries

Virology Laboratory CRESAR/IMPM/Institut de Recherche pour le Développement, Yaoundé, Cameroon.
Antiviral therapy (Impact Factor: 3.02). 01/2009; 14(3):401-11.
Source: PubMed


The rapid expansion of antiretroviral treatment in resource-limited settings is raising concerns regarding the emergence and transmission of HIV drug resistance (HIVDR). We evaluated the extent of transmission of drug-resistant HIV strains in four Central African countries: the Republic of Congo, Central African Republic, Chad and Cameroon.
The World Health Organization (WHO) HIVDR threshold survey was implemented in major treatment areas in each country. Pregnant women who were aged <25 years, who were at first pregnancy and who were HIV type-1-positive were enrolled at each site in 2006-2007 for genotyping. HIVDR prevalence was categorized using the WHO threshold survey binomial sequential sampling method.
The prevalence of HIVDR in Brazzaville and Bangui sites could not be classified because the eligible sample number was not reached. HIVDR prevalence was low (<5%) in N'Djamena for all drug classes. In Yaoundé, we found one individual with the D67D/N mutation and two with K103N. HIVDR prevalence was categorized as low (<5%) for protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), and moderate (> or =5-< or =15%) for non-NRTIs (NNRTIs). HIVDR prevalence in Douala was low for PIs and NNRTIs, and moderate for NRTIs as we identified one individual with M184V plus K101E plus G190A mutations and a second with D67D/N.
The moderate HIVDR prevalence found in Yaoundé and Douala indicate that efforts should be made in Cameroon to prevent HIVDR; however, additional surveys are needed to confirm this trend. This study highlighted challenges presented by the WHO methodology, such as additional costs, workload, difficulties in acquiring even small sample numbers and the necessity for better quality assurance of HIV testing and record keeping at antenatal clinics.

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    • "Continuous staff training is essential to sustain good practices; brain drain makes the heavy workload persistent, thereby calling for policies to train and retain qualified personnel, especially with the need/creation of new ART clinics in the country to ensure scaling-up of the treatment programmes [36]. More importantly, recent studies in Cameroon showed low to moderate levels of transmitted HIVDR [40], and increasing levels of acquired HIVDR after 12 and 24 months [41], thus predicting growing risks of treatment failure and HIVDR to the commonly used drugs, due to a broad range of factors [35,39]. Without attempting to create a direct temporal relationship, the increasing rate of transmitted and acquired HIVDR in Cameroon, alongside the increasing/widely availability of ARV treatment, supports also a growing need of affordable viral load and HIVDR testing, and a more regular surveillance of HIVDR in this country [8,38]. "
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    ABSTRACT: Background Rapid scale-up of antiretroviral therapy (ART) and limited access to genotyping assays in low-resource settings (LRS) are inevitably accompanied by an increasing risk of HIV drug resistance (HIVDR). The current study aims to evaluate early warning indicators (EWI) as an efficient strategy to limit the development and spread of preventable HIVDR in these settings, in order to sustain the performance of national antiretroviral therapy (ART) rollout programmes. Methods Surveys were conducted in 2008, 2009 and 2010 within 10 Cameroonian ART clinics, based on five HIVDR EWIs: (1) Good prescribing practices; (2) Patient lost to follow-up; (3) Patient retention on first line ART; (4) On-time drug pick-up; (5) Continuous drug supply. Analysis was performed as per the World Health Organisation (WHO) protocol. Results An overall decreasing performance of the national ART programme was observed from 2008 to 2010: EWI1 (100% to 70%); EWI2 (40% to 20%); EWI3 (70% to 0%); EWI4 (0% throughout); EWI5 (90% to 40%). Thus, prescribing practices (EWI1) were in conformity with national guidelines, while patient adherence (EWI2, EWI3, and EWI4) and drug supply (EWI5) were lower overtime; with a heavy workload (median ratio ≈1/64 staff/patients) and community disengagement observed all over the study sites. Conclusions In order to limit risks of HIVDR emergence in poor settings like Cameroon, continuous drug supply, community empowerment to support adherence, and probably a reduction in workload by task shifting, are the potential urgent measures to be undertaken. Such evidence-based interventions, rapidly generated and less costly, would be relevant in limiting the spread of preventable HIVDR and in sustaining the performance of ART programmes in LRS.
    BMC Public Health 04/2013; 13(1):308. DOI:10.1186/1471-2458-13-308 · 2.26 Impact Factor
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    • "The huge genetic variability of HIV-1 results in a complex and dynamic molecular classification of types (HIV-1 and 2), groups (M,N,O,P), and the pandemic group M could be divided into subtypes (A-D,F-H,J,K) and recombinant forms, such as circulating recombinant forms (CRF) and unique recombinant forms (URF). Such HIV-1 variation has an important impact on diagnosis, viral load measurement and the performance of HIV-1 genotyping systems [1-3]. Thus, HIV-1 subtypes also contribute to the capacity of HIV-1 to evade the host immune response, [4] which can affect the response to antiretroviral treatment and, consequently, to the emergence of drug resistance [5]. "
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    ABSTRACT: BACKGROUND: The city of Sao Paulo has the highest AIDS case rate, with nearly 60% in Brazil. Despite,several studies involving molecular epidemiology, lack of data regarding a large cohort studyhas not been published from this city.Objectives This study aimed to describe the HIV-1 subtypes, recombinant forms and drug resistancemutations, according to subtype, with emphasis on subtype C and BC recombinants in thecity of São Paulo, Brazil.Study designRNA was extracted from the plasma samples of 302 HIV-1-seropositive subjects, of which211 were drug-naive and 82 were exposed to ART. HIV-1 partial pol region sequences wereused in phylogenetic analyses for subtyping and identification of drug resistance mutations.The envelope gene of subtype C and BC samples was also sequenced. RESULTS: From partial pol gene analyses, 239 samples (79.1%) were assigned as subtype B, 23 (7.6%)were F1, 16 (5.3%) were subtype C and 24 (8%) were mosaics (3 CRF28/CRF29-like). Thesubtype C and BC recombinants were mainly identified in drug-naïve patients (72.7%) andthe heterosexual risk exposure category (86.3%), whereas for subtype B, these values were69.9% and 57.3%, respectively (p = 0.97 and p = 0.015, respectively). An increasing trend ofsubtype C and BC recombinants was observed (p < 0.01). CONCLUSION: The HIV-1 subtype C and CRFs seem to have emerged over the last few years in the city ofSão Paulo, principally among the heterosexual population. These findings may have animpact on preventive measures and vaccine development in Brazil.
    Virology Journal 08/2012; 9(1):156. DOI:10.1186/1743-422X-9-156 · 2.18 Impact Factor
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    • "This result is in accordance with previous studies conducted in Cameroon that reported rates of drug-resistance transmission among drugnaı¨ve individuals ranging from 4.9 to 9.8% [Vergne et al., 2006; Vessière et al., 2006; Ndembi et al., 2008; Aghokeng et al., 2009]. It is important to take into consideration that in this study TDR mutations were found exclusively in pediatric population: This evidence could be explained by the low number of naive adult patients analyzed (8/49). "
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    ABSTRACT: Currently the prevalence of HIV-1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV-1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV-1 genetic diversity and to characterize HIV-1 mutations conferring drug resistance among antiretroviral therapy (ART)-naïve and ART-treated patients. A cohort of 239 patients infected with HIV were followed-up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV-1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first-line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second-line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care.
    Journal of Medical Virology 05/2012; 84(5):721-7. DOI:10.1002/jmv.23244 · 2.35 Impact Factor
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