High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat

Abstract

Background: The feasibility of antiretroviral therapy (ART) monitoring remains problematic in decentralized HIV clinic settings of sub-Saharan Africa. We assessed the rates and correlates of HIV-1 virological failure (VF) and drug resistance (DR) in 2 pre-test-and-treat urban clinic settings of Senegal. Methods: Consenting HIV-1-infected adults (⩾18 years) receiving first-line ART for ⩾12 months were cross-sectionally enrolled between January and March 2015, at the referral outpatient treatment center of Dakar (n = 151) and decentralized regional hospital of Saint-Louis (n = 127). In the 12 months preceding plasma specimens’ collection patients at Saint-Louis had no viral load (VL) testing. Significant predictors of VF (VL ⩾ 1000 copies/ml) and DR (clinically relevant mutations) were determined using binomial logistic regression in R software. Results: Of the 278 adults on EFV-/NVP-based regimens, 32 (11.5% [95%CI: 8.0-15.9]) experienced VF. Failing and non-failing patients had comparable median time [interquartile] on ART (69.5 [23.0-89.5] vs 64.0 [34.0-99.0] months; P = .46, Mann–Whitney U-test). Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). The pattern of mutations did not always correspond to the ongoing treatment. The adjusted odds of VF was significantly associated with the decentralized clinic site ( P < .001) and CD4 < 350 cells/mm3 ( P < .006). Strong correlates of DR also included Saint-Louis ( P < .009), CD4 < 350 cells/mm3 ( P <. 001), and nevirapine-based therapies (comparator: efavirenz-based therapies; P < .027). In stratification analyses by site, higher rate of VF at Saint-Louis (20.5% [95%CI: 13.8-28.5] vs 4.0% [95%CI: 1.5-8.5] in Dakar) was associated with nevirapine-based therapies (OR = 3.34 [1.07-11.75], P = .038), self-reported missing doses (OR = 3.30 [1.13-10.24], P = .029), and medical appointments (OR = 2.91 [1.05-8.47], P = .039) in the last 1 and 12 months(s), respectively. The higher rate of DR at Saint-Louis (12.9% [95%CI: 7.6-20.1] vs 2.7% [95%CI: 0.7-6.7] in Dakar) was associated with nevirapine-based therapies (OR = 5.13 [1.12-37.35], P = .035). Conclusion: At decentralized urban settings, there is need for enhanced virological monitoring and adherence support. HIV programs in Senegal should intensify early HIV diagnosis for effective test-and-treat. These interventions, in addition to the superiority of efavirenz-based therapies provide a favorable framework for transitioning to the recommended potent drug dolutegravir, thereby ensuring its long-term use.

HIV-1 drug resistance and genetic diversity in people with HIV-1 in Cape Verde

“…The pattern and frequency of the most common mutations, such as M184V/I (43%), TAMs (M41L, D67N, K70E/R, L210W, T215F/I/L/V/Yand K219Q/ E) (29%), K103N/S (36%), G190A/S (19%) and V106A/ I/M (12%) were similar to previous reports from Cape Verde and other low-income and middle-income countries [16][17][18][19][20][21][22][23][24][35][36][37] and consistent with the preferred first-line regimen of our patients…”

“…The pattern and frequency of the most common mutations, such as M184V/I (43%), TAMs (M41L, D67N, K70E/R, L210W, T215F/I/L/V/Y and K219Q/E) (29%), K103N/S (36%), G190A/S (19%) and V106A/I/M (12%) were similar to previous reports from Cape Verde and other low-income and middle-income countries [16–24,35–37] and consistent with the preferred first-line regimen of our patients, AZT + 3TC + NVP (46%) or TDF + FTC/3TC + EFV (31%). Directly related to the presence of the DRMs, most people with virological failure showed HLR to, NVP (67%) and EFV (64%), arguing against the use of these first-generation NNRTIs in Cape Verde without first performing a genotypic drug resistance assay.…”

Performance of Xpert HIV-1 viral load test in Senegal: a country of high circulation of CRF02_AG

“…Indeed, many studies in Senegal highlighted the great diversity of HIV-1 strains with a predominance of non-B and non-C subtypes, mainly circulating recombinant forms. CRF02_AG remains the predominant strain in the country with more than 55% over the years [ 19 , 31 , 32 ]. This evaluation, carried out in this context, showed however an excellent correlation and concordance between platforms with a Pearson coefficient r=0.985 and a mean difference of 0.0075 log10 copies/ml.…”

HIV-1 genotypic profiling ensures effective response to third-line antiretroviral therapy in Cameroon

“…[1] This progress, over the last decade, is a result of ART scale-up which has dramatically reduced human immunodeficiency virus (HIV)-related morbidity and mortality even in resource-limited settings (RLS), including sub-Saharan Africa (SSA). [1][2][3][4][5][6] However, achieving a sustained undetectable viral load (VL) ( < 50copies/mL) remains a major challenge due to emerging HIV drug resistance (HIVDR) strains, especially with the growing number of heavily-treated patients. [7][8][9][10][11] Of note, a systematic review and meta-analysis reported 19% of patients failing second-line after 12 to 18 months in SSA.…”