Determinants of HIV-1 virological failure and acquired drug resistance with regard to decentralization of HIV care
Background: Tremendous efforts with increased access to antiretroviral therapy (ART) in sub-Saharan Africa have led to reductions in AIDS-related morbidity and mortality. Howev-er, the gaps with HIV monitoring services denote that patients in decentralized settings, in particular, are not optimally managed - which could undermine the attainment of the 90-90-90 treatment goals. We assessed the prevalence and determinants of virological failure (VF) and acquired drug resistance (ADR) amongst patients undergoing first-line ART in Senegal.    Methods: In this cross-sectional design, HIV-1-infected adults (=18 years) on ART for =12 months had viral load (VL) measurements between January-March 2015. Patients were re-cruited at the ambulatory treatment center of Dakar (n=157) and, the decentralized site of Saint-Louis' regional hospital (n=121). VF outcome was expressed as unsuppressed VL=1000 copies/ml and, ADR as evidence of at least one resistance-associated mutation. Binomial lo-gistic odds ratios (OR) and 95% confidence intervals ([CI]) and, ?2/Fisher-Exact, were used to determine significant predictors of VF and ADR, respectively.  Results: Of the 278 enrolled patients on TDF-/AZT-based regimens over a cumulative medi-an duration of 64 months, 32 had VF (11.5%, 95% CI [8.01-15.86]) while 21 had ADR (7.5%, 95% CI [4.74-11.32]). Determinants of VF in multivariable adjustments were: Saint-Louis (vs. Dakar: OR, 5.0; 95% CI [1.98-14.7]; p<0.001), CD4=500 cells/mm3 (CD4<350: OR, 4.82; 95% CI [1.87-13.0]; CD4=350=500: OR, 1.63; 95% CI [0.48-5.1]; p=0.004) and, missed medical appointment (vs. not missed: OR, 2.32; 95% CI [1.0-5.44]; p=0.048). ADR was higher in Saint-Louis than Dakar (13.4% vs. 2.65%, p<0.001). Other strong correlates of ADR included CD4=500 cells/mm3 and VL>10000 copies/ml. The pattern of ADR across drug regimens was: NVP>3TC>AZT>TDF>EFV>FTC. Of the samples successfully geno-typed (27/32), prevalent ADR mutations to NRTIs (n=17) were M184VI (n=16), K65R/T215SY (n=5) and to NNRTIs, K103N (n=10), Y181CY (n=6), A98AG (n=5). Conclusion: Being on care in Saint-Louis, having lower CD4 counts and higher VL, predis-posed more to VF and ADR. The interplay between these variables indicates more inherent health facilities based challenges. In line with the 90-90-90 targets for 2020, health systems - including those at decentralized settings - need to strengthen prompt diagnosis and treatment initiation, virological monitoring and counselling.