Date Published: November 28, 2017
Publisher: Public Library of Science
Author(s): Jacob Bor, Matthew P. Fox, Sydney Rosen, Atheendar Venkataramani, Frank Tanser, Deenan Pillay, Till Bärnighausen, Noah Kiwanuka
Abstract: BackgroundLoss to follow-up is high among HIV patients not yet receiving antiretroviral therapy (ART). Clinical trials have demonstrated the clinical efficacy of early ART; however, these trials may miss an important real-world consequence of providing ART at diagnosis: its impact on retention in care.Methods and findingsWe examined the effect of immediate (versus deferred) ART on retention in care using a regression discontinuity design. The analysis included all patients (N = 11,306) entering clinical HIV care with a first CD4 count between 12 August 2011 and 31 December 2012 in a public-sector HIV care and treatment program in rural South Africa. Patients were assigned to immediate versus deferred ART eligibility, as determined by a CD4 count < 350 cells/μl, per South African national guidelines. Patients referred to pre-ART care were instructed to return every 6 months for CD4 monitoring. Patients initiated on ART were instructed to return at 6 and 12 months post-initiation and annually thereafter for CD4 and viral load monitoring. We assessed retention in HIV care at 12 months, as measured by the presence of a clinic visit, lab test, or ART initiation 6 to 18 months after initial CD4 test. Differences in retention between patients presenting with CD4 counts just above versus just below the 350-cells/μl threshold were estimated using local linear regression models with a data-driven bandwidth and with the algorithm for selecting the bandwidth chosen ex ante. Among patients with CD4 counts close to the 350-cells/μl threshold, having an ART-eligible CD4 count (<350 cells/μl) was associated with higher 12-month retention than not having an ART-eligible CD4 count (50% versus 32%), an intention-to-treat risk difference of 18 percentage points (95% CI 11 to 23; p < 0.001). The decision to start ART was determined by CD4 count for one in four patients (25%) presenting close to the eligibility threshold (95% CI 20% to 31%; p < 0.001). In this subpopulation, having an ART-eligible CD4 count was associated with higher 12-month retention than not having an ART-eligible CD4 count (91% versus 21%), a complier causal risk difference of 70 percentage points (95% CI 42 to 98; p < 0.001). The major limitations of the study are the potential for limited generalizability, the potential for outcome misclassification, and the absence of data on longer-term health outcomes.ConclusionsPatients who were eligible for immediate ART had dramatically higher retention in HIV care than patients who just missed the CD4-count eligibility cutoff. The clinical and population health benefits of offering immediate ART regardless of CD4 count may be larger than suggested by clinical trials.
Partial Text: Mass provision of HIV treatment has improved life expectancy in southern Africa [1–3], yet HIV remains the leading cause of death and disability . Recent clinical trials show health benefits to antiretroviral therapy (ART) at high CD4 counts [5–7]; WHO now recommends starting HIV patients on ART at diagnosis , and many countries have moved to “treat all” policies .
Understanding the extent to which immediate ART initiation mitigates loss of health and life due to failure to remain in care is important for countries and funding agencies considering WHO recommendations to start patients immediately on therapy regardless of CD4 count [8,9]. Although lower retention has been observed in pre-ART patients compared to ART patients in a wide range of settings, it was hitherto unknown whether this reflected a causal relationship or selection of highly motivated patients onto ART [11,12]. If starting ART causally increased retention in care, then the real-world benefits of immediate ART would be underestimated in clinical trials that actively retain patients not yet eligible for therapy [5–7].