Starting antiretroviral therapy (ART) immediately following an HIV diagnosis dramatically improves retention in clinical HIV care, according to a study led by a Boston University School of Public Health researcher. The study suggests that the benefits of providing immediate ART may be larger than previously thought.
“Treatment outcomes are a result of both biological efficacy and patient behaviour. Extending HIV treatment eligibility to patients at diagnosis substantially increases retention in care, an effect not observed in prior trials,” says lead author Jacob Bor, assistant professor of global health.
In the past, ART eligibility was determined based on the CD4 cell count in patients diagnosed with HIV. Now, however, the World Health Organisation recommends that countries start patients immediately on ART regardless of CD4 count. Understanding the expected benefits of this “treat all” approach, the authors wrote, is particularly important for countries like South Africa, where HIV remains the leading cause of death and disability in the country despite the mass provision of treatment.
“Patients denied therapy under older guidelines often dropped out of care altogether, leading to worse outcomes,” Bor says. “We show that extending HIV treatment eligibility to these patients significantly increased their chances of staying in care.”
The researchers assessed the association between immediate versus deferred therapy and the subsequent rate of patients lost from HIV care among 11,306 patients in a large public-sector treatment program in rural South Africa. Using a regression-discontinuity design, they compared 12-month retention in care among patients presenting just below the threshold for ART eligibility (350-cells/μl CD4) versus those presenting just above.
The researchers found that patients who were immediately eligible for ART at diagnosis were 25 percentage points more likely to start therapy and were 18 percentage points more likely to remain in clinical HIV care at 12 months, compared to patients who were not eligible for immediate therapy. Among patients whose treatment decision was based on their CD4 count, having an eligible CD4 count increased 12-month retention rate from 21% to 91%, a 70 percentage-point increase.
“A key feature of this study is the quasi-experimental approach, which enables us to evaluate the real-world effect of HIV treatment eligibility on retention in care,” Bor says.
“Effects on patient care-seeking behaviours cannot be observed in clinical trials that minimize attrition by design.”
Other SPH authors were Matthew Fox, professor of epidemiology, and Sydney Rosen, research professor of global health. Other co-authors included: Atheendar Venkataramani, assistant professor of medicine at Massachusetts General Hospital, Frank Tanser, professor at Africa Health Research Institute, Deenan Pillay, professor Africa Health Research Institute, and Till Bärnighausen, professor at Heidelberg University.
Background: Loss 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 findings: We 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.
Conclusions: Patients 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.
Jacob Bor, Matthew P Fox, Sydney Rosen, Atheendar Venkataramani, Frank Tanser, Deenan Pillay, Till Bärnighausen