Predictors of Time-to-ART-Initiation Survival Times in a Random Sample of Adults Living with HIV from Malawi – A Historical, Nationally Representative Cohort Sample of 2004-2015 HIV Data

Abstract

ABSTRACTBackgroundDespite globally adapted universal test-and-treat (UTT) strategy of HIV management, survival time-to-antiretroviral-therapy initiation (TTAT) remains heterogenous and affected by diverse factors which remain unexplained in Malawi. This study explored correlates to TTAT-initiation in Malawi among adults living with HIV.MethodsA multicentre retrospective cohort study was undertaken from eight centres. Medical records of (n=9,953) adult patients aged 15+ years old, were reviewed. A life table, the Kaplan-Meier log-rank, and Cox Proportion Hazard regression were used to calculate survival TTAT-initiation and its correlates, respectively. Adjusted Hazard ratio less than 1 (aHR <1) signified factors negatively associated, while aHR >1 meant factors positively associated with TTAT-initiation. Hazard ratio with 95% Confidence interval (95%CI) andp<0.05 were used to declare statistical significance.ResultsData from (n=9,953) adult HIV patients were abstracted from hospital medical records. Patients median age was 40 (IQR: 33-48 years). 60.8% were females, 45.2% were younger adults of 20-39 years, and 78.8% were either married or cohabiting. 48.1% had advanced HIV disease; WHO clinical stage III, 24.5% had WHO stage IV, whereas 27.5% were asymptomatic; thus; 24.9% initiated ART due to low CD4+ count and 2.6% under PMTCT’s Option-B+. Findings from TTAT-initiation survival function analysis show that each patient had a single entry into the study and provided a total of 5,414 event-time-intervals, giving a 100% total event-failure without censored observations. Mean and median survival times were 527.2 days and 6 (IQR 0-5,414) days, respectively. Treatment-initiation (time at risk) was observed at the rate of 0.002 per 5,247,268 person-years. From multivariable Cox PH regression analysis, independent factors identified to be negatively associated with early (timely) antiretroviral treatment-initiation included; older age of 55+ years by 16% [aHR 0.84, 95%CI: (0.71–0.97)], male gender by 4% [aHR=0.96, 95%CI: (0.92–0.98)], bacterial causes by 5% [aHR=0.95, 95%CI: (0.89–0.99)], mycobacterial causes by 14% [aHR=0.86, 95%CI: (0.81–0.92)], high viraemia VL>1,000 copies/mL by 17% [aHR=0.83, 95%CI: (0.81–0.95)], registered in secondary tier and tertiary tier health facilities by 21% [aHR 0.79, 95%CI: (0.73-0.86) and 14% [aHR 0.86, 95%CI: (0.79-0.93) respectively, longer HIV survivorship (duration) by 58% to 85%, and having respiratory symptoms like coughing or breathlessness by 7% [0.93 95%CI: (0.88–0.97)]. These factors acted as barriers to early time-to-ART-initiation. In contrast younger adults of 20-39 years; [aHR=1.04, 95%CI: (1.02–1.19)], early mid-aged patients of 40-54 years; [aHR=1.03, 95%CI: (1.01– 1.21)], incomplete basic education level; [aHR 1.09, 95%CI: (1.02-1.20)], secondary education level; [aHR=1.06, 95%CI: (1.01-1.12)], Northern and Southern regions ethnicity; [aHR=1.07, 95%CI: (1.02–1.16)] and [aHR=1.06, 95%CI: (1.01–1.12) respectively, manifesting chronic headache or fevers; [aHR=1.12, 95%CI: (1.04–1.21)], being asymptomatic; [aHR=1.02, 95%CI: (1.02–1.13), (p<0.041)], being immunosuppressed with WHO clinical stage III; [aHR=1.86, 95%CI: (1.21-3.45)], WHO clinical stage IV; [aHR=2.80, 95%CI: (1.20-3.22)], protozoal pathological infection; [aHR=1.06, 95%CI: (1.02-1.15)], low CD4+ cell count <250 cells/µL; [aHR=1.05, 95%CI: (1.01–1.09), self-employment [aHR=1.04, 95%CI: (1.00–1.09)], and year of HIV diagnosis variable, were all positively associated with treatment-initiation and acted as precursors to early (timely) ART-initiation.ConclusionThe study demonstrates that apart from meeting clinical eligible, different clinical and nonclinical factors contributed to time-to-treatment initiation among adults living with HIV. These factors; which are still prevalent in Malawi, have contributed to the spiralling and high mortality and morbidity from HIV/AIDS in Malawi and– hence, a knowledge of their existence, coupled with efforts to counteract and halt their occurrences, and strategies to strengthen and sustain the gained milestones in all tiers of health facility establishments across Malawi cannot be overemphasised.