HIV-1 Genetic Diversity and Drug Resistance among Senegalese Patients in the Public Health System

Moussa Thiam, a Halimatou Diop-Ndiaye, a Aminata Diaw Diouf, a Nicole Vidal, b Ousseynou Ndiaye, a Ibrahima Ndiaye, c Ndeye Fatou Ngom-Gueye, d Sada Diallo, a Oumy Diop Diongue, a Makhtar Camara, a Abdoulaye Seck, a Souleymane Mboup, a Coumba Toure-Kanea Laboratoire de Bactériologie-Virologie, Hôpital Le Dantec, Dakar, Senegala ; UMI 233, IRD, Montpellier, Franceb ; Centre Régional de Recherche et Formation sur le VIH/SIDA, Université Cheikh Anta Diop, Dakar, Senegalc ; Centre de Traitement Ambulatoire, CHU de Fann, Dakar, Senegald In this study, we investigated the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations and genetic variability among Senegalese patients undergoing highly active antiretroviral therapy (ART) in the public health system. We conducted a cross-sectional study of 72 patients with suspected therapeutic failure. HIV-1 genotyping was performed with Viroseq HIV-1 Genotyping System v2.0 or the procedure developed by the ANRS AC11 resistance study group, and a phylogenetic analysis was performed. The median follow-up visit was at 40 (range, 12 to 123) months, and the median viral load was 4.67 (range, 3.13 to 6.94) log10 copies/ml. The first-line therapeutic regimen was nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) or NRTIs plus nevirapine (NVP) (54/72 patients; 75%), and the second-line therapy was NRTIs plus a protease inhibitor (PI/r) (18/72; 25%). Fifty-five patients (55/72; 76.39%) had at least one drug resistance mutation. The drug resistance rates were 72.22 and 88.89% for the first-line and second-line ARTs, respectively. In NRTI mutations, thymidine analog mutations (TAMs) were found in 50.79% and the M184V mutation was found in 34.92% of the samples. For non-NRTI resistance, we noted a predominance of the K103N mutation (46.27%). For PI/r, several cases of mutations were found with a predominance of M46I and L76V/F at 24% each. The phylogenetic analysis revealed CRF02_AG as the predominant circulating recombinant form (43/72; 59.72%). We found a high prevalence of resistance mutations and a high rate of TAMs among Senegalese patients in the public health system. These findings emphasize the need to improve virological monitoring in resource-limited settings. P hylogenetic analyses of many HIV-1 strains isolated from diverse geographic origins have revealed four distinct groups of viruses, namely, groups M, N, O, and P. Group M, which is responsible for the global pandemic, can be further subdivided into subtypes (A to D, F to H, J, and K), subsubtypes, and numerous circulating recombinant forms (CRF01 to CRF54; . circulating HIV-1 strains have been characterized and show a high level of genetic diversity, with the predominance of CRF02_AG among members of the general population (1, 2) and female sex workers (3). However, a high prevalence of subtype C was noted among men who have sex with men (4). In developing countries where non-B subtypes are predominant, antiretroviral therapy (ART) has become increasingly available, resulting in the improved health and survival of patients infected with HIV-1. The emergence of HIV resistance, due to mutations in the viral protease and reverse transcriptase (RT) genes, is the major cause of ART failure. The development of drug resistance requires the occurrence of both antiretroviral drug exposure and ongoing viral replication (5). One of the first ART initiatives sponsored by an African government was launched in Senegal in 1998. Patients were monitored clinically and biologically by plasma HIV-1 RNA load determination, CD4 cell counting at the baseline and at 6-month time intervals, and monthly medical examinations (6). According to the 2010 World Health Organization (WHO) guidelines, the first-line drug regimen for adults and adolescents in resource-limited settings should contain two nucleoside RT inhibitors (NRTIs) and one non-NRTI (NNRTI). After first-line ART failure, a boosted protease inhibitor with two NRTIs has been recommended for second-line ART (7). In a prospective observational cohort study, it was shown that the implementation of highly active ART (HAART), in combination with clinical, biological, and logistical monitoring, reduced the emergence of resistant strains in Africa (8). The WHO guidelines also suggest that the first-line ART regimen should be switched after immunological or clinical failure when plasma HIV-1 RNA load tests are not available (7). However, previous studies reported the development of resistance mutations when the switch was performed solely on the basis of immunological or clinical monitoring of patients (9, 10). A similar study of patients receiving first-line ART in Africa revealed a high rate of thymidine analog mutation (TAM) accumulation in patients with immunological or clinical failure when following the WHO guidelines (11). Most published data on ART treatment in Senegal have resulted from structural prospective studies, including a biological follow-up study according to the best standards of care (6, 12, 13). However, no data on HIV drug resistance (HIVDR) was available from patients undergoing HAART in the public health system. The aim of this study was to investigate the prevalence of HIVDR mutations and the genetic diversity in a routinely treated general population group. Received 14 September 2012 Returned for modification 31 October 2012 Accepted 30 November 2012 Published ahead of print 12 December 2012 Address correspondence to Coumba Toure-Kane, . Copyright © 2013, American Society for Microbiology. All Rights Reserved. doi:10.1128/JCM.02452-12 578 Journal of Clinical Microbiology p.