RESUMO
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.
RESUMO
OBJECTIVES: Disruption in HIV care provision may enhance the development and spread of drug resistance due to inadequate antiretroviral therapy. This study thus determined the prevalence of HIV-1 transmitted drug resistance (TDR) in settings of decentralized therapy and care in Senegal and, the Ebola outbreak in Guinea. Antiretroviral-naïve patients were enrolled following a modified WHO TDR Threshold Survey method, implemented in Senegal (January-March 2015) and Guinea (August-September 2015). Plasma and dried blood spots specimens, respectively from Senegalese (n = 69) and Guinean (n = 50) patients, were collected for direct sequencing of HIV-1 pol genes. The Stanford Calibrated Population Resistance program v6.0 was used for Surveillance Drug Resistance Mutations (SDRMs). RESULTS: Genotyping was successful from 54/69 (78.2%) and 31/50 (62.0%) isolates. In Senegal, TDR prevalence was 0% (mean duration since HIV diagnosis 4.08 ± 3.53 years). In Guinea, two patients exhibited SDRMs M184V (NRTI), T215F (TAM) and, G190A (NNRTI), respectively. TDR prevalence at this second site, however, could not be ascertained because of low sample size. Phylogenetic inference confirmed CRF02_AG predominance in Senegal (62.96%) and Guinea (77.42%). TDR prevalence in Senegal remains extremely low suggesting improved control measures. Continuous surveillance in both settings is mandatory and, should be done closest to diagnosis/transmission time and with larger sample size.
