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

Abstract

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) log 10 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.

Pseudomembranous Candidiasis Indicates High Level Drug Resistance among Patients on Antiretroviral Treatment in Nairobi East District, Kenya

“…Comparison with data from the previous studies [1][2][3][4]6,7] was also limited due to wide variations in duration of patients on ART and in the 'high HIV-RNA plasma level' cut offs which ranged from 2,000 -100,000 copies/ml. It was remarkable to observe that although a selected group of patients participated in our study, the high prevalence of mutations including TAMs was consistent with that of a larger study [9].…”

“…Drug resistance mutations include thymidine associated analogue mutations (TAMs) which induce high level resistance to most NRTIs. Continuation of ART in the presence of ongoing viral replication leads to increasing ART resistance formation whereby options for second-line treatment will decrease over time, especially if TAMs are accumulating [8,9]. Furthermore, resistant viruses may be transmitted to others whose response to first-line treatment may thereby be compromised.…”

The Prediction of Integrase Inhibitors Efficacy in Third Line Regimen after First and Second Line Antiretroviral Therapy Failure in Senegal

“…For 55 months of median ART follow up duration, at least one DRM was found in 55.8% (n=29/52) of patients on first line, which is not significantly different (p=0.07) that previously observed in Senegal [7]. Similar results have been reported in Cameroon [22,23], in Republic of Central Africa [24] and in Republic of South Africa [25].…”

“…Reported to the study population, the prevalence of DRM was (23.07%; 12/52). This finding is significantly lower than previously reported in Senegal (p<0.01) and Mali (p<0.01) [7,27]. The differences could be explained by the longer second line ART median duration (4 years) for the study conducted in Mali and the limited sample size of the study in Senegal.…”

“…On the contrary, for patients followed through the National Program based on public health approach in Senegal as well as in other African countries where HIV-1 RNA viral load tests are not always available, WHO has recommended the use the immunological or clinical criteria to switch the first line ART [6]. Results from these patients showed a high rate of drug resistance mutations and an accumulation of the thymidine analog mutations (TAMs) both for the patients under first and second line ART in Senegal [7]. In this study the main limit was the low number of patients on second line compared to the total of patients under 2 nd line biologically followed based on the database at the Bacteriology and Virology Laboratory.…”