Contemporary disengagement from antiretroviral therapy in Khayelitsha, South Africa: A cohort study

Abstract

Background: Retention in care is an essential component of meeting the UNAIDS "90-90-90" HIV treatment targets. In Khayelitsha township (population ~500,000) in Cape Town, South Africa, more than 50,000 patients have received antiretroviral therapy (ART) since the inception of this public-sector program in 2001. Disengagement from care remains an important challenge. We sought to determine the incidence of and risk factors associated with disengagement from care during 2013-2014 and outcomes for those who disengaged.

Methods and findings: We conducted a retrospective cohort study of all patients ≥10 years of age who visited 1 of the 13 Khayelitsha ART clinics from 2013-2014 regardless of the date they initiated ART. We described the cumulative incidence of first disengagement (>180 days not attending clinic) between 1 January 2013 and 31 December 2014 using competing risks methods, enabling us to estimate disengagement incidence up to 10 years after ART initiation. We also described risk factors for disengagement based on a Cox proportional hazards model, using multiple imputation for missing data. We ascertained outcomes (death, return to care, hospital admission, other hospital contact, alive but not in care, no information) after disengagement until 30 June 2015 using province-wide health databases and the National Death Registry. Of 39,884 patients meeting our eligibility criteria, the median time on ART to 31 December 2014 was 33.6 months (IQR 12.4-63.2). Of the total study cohort, 592 (1.5%) died in the study period, 1,231 (3.1%) formally transferred out, 987 (2.5%) were silent transfers and visited another Western Cape province clinic within 180 days, 9,005 (22.6%) disengaged, and 28,069 (70.4%) remained in care. Cumulative incidence of disengagement from care was estimated to be 25.1% by 2 years and 50.3% by 5 years on ART. Key factors associated with disengagement (age, male sex, pregnancy at ART start [HR 1.58, 95% CI 1.47-1.69], most recent CD4 count) and retention (ART club membership, baseline CD4) after adjustment were similar to those found in previous studies; however, notably, the higher hazard of disengagement soon after starting ART was no longer present after adjusting for these risk factors. Of the 9,005 who disengaged, the 2 most common initial outcomes were return to ART care after 180 days (33%; n = 2,976) and being alive but not in care in the Western Cape (25%; n = 2,255). After disengagement, a total of 1,459 (16%) patients were hospitalized and 237 (3%) died. The median follow-up from date of disengagement to 30 June 2015 was 16.7 months (IQR 11-22.4). As we included only patient follow-up from 2013-2014 by design in order to maximize the generalizability of our findings to current programs, this limited our ability to more fully describe temporal trends in first disengagement.

Conclusions: Twenty-three percent of ART patients in the large cohort of Khayelitsha, one of the oldest public-sector ART programs in South Africa, disengaged from care at least once in a contemporary 2-year period. Fifty-eight percent of these patients either subsequently returned to care (some "silently") or remained alive without hospitalization, suggesting that many who are considered "lost" actually return to care, and that misclassification of "lost" patients is likely common in similar urban populations. A challenge to meeting ART retention targets is developing, testing, and implementing program designs to target mobile populations and retain them in lifelong care. This should be guided by risk factors for disengagement and improving interlinkage of routine information systems to better support patient care across complex care platforms.

Fig 1. Flow diagram of study cohort.

ART, antiretroviral therapy.

Fig 2. Cumulative incidence (competing risks analysis) of disengagement, transfer (including silent transfers), and mortality, as estimated by a flexible parametric survival model based on time to disengagement from cohort entry date to 31 December 2014.

Fig 3

(a) Cumulative incidence (competing risks analysis) of disengagement, transfer (including silent transfers), and mortality, as estimated by a flexible parametric survival model based on time contributed during a 2-year period, but analyzed relative to ART initiation date, allowing for delayed entry into the analysis. (b) Hazard of disengagement by duration since ART start, with calendar year (2013 versus 2014) fitted as a time-varying covariate in a Cox proportional hazards model. (c) Hazard of disengagement by duration since ART start, with calendar year (2013 versus 2014) fitted as a time-varying covariate in a Cox proportional hazards model adjusted for the patient characteristics listed in Table 2. ART, antiretroviral therapy.

Fig 4. Map of Western Cape province indicating clinics where silent transfers and patients who disengaged returned to care until 30 June 2015.

DOH, Department of Health. Sources: Basemap: Used with permission. Copyright 2017 Esri, ArcGIS Desktop, Western Cape Department of Health, and the GIS User Community. CC BY 4.0. South African Department of Health Layer: Boundaries of the Department of Health Sub-districts falling under the authority of the Western Cape Government and the City of Cape Town municipality (data provided June 2016 by Deputy Director, Information Management Health, Western Cape Government, South Africa). South African public health facilities layer: Locations of facilities falling under the authority of the Western Cape Government and the City of Cape Town. Includes some Inactive facilities as listed in the operational Sinjani system (data provided June 2016 by Deputy Director, Information Management Health, Western Cape Government, South Africa). Software: ESRI 2016. ArcGIS Desktop: version 10.4. Redlands, CA: Environmental Systems Research Institute.