The Effect of Timing of Initiation of Antiretroviral Therapy on Loss to Follow-up in HIV–Tuberculosis Coinfected Patients in South Africa: An Open-Label, Randomized, Controlled Trial

Abstract

To evaluate the effect of early integrated, late-integrated, and delayed antiretroviral therapy (ART) initiation during tuberculosis (TB) treatment on the incidence rates of loss to follow-up (LTFU) and to evaluate the effect of ART initiation on LTFU rates within trial arms in patients coinfected with TB and HIV. A substudy within a 3-armed, open label, randomized, controlled trial. Patients were randomized to initiate ART either early or late during TB treatment or after the TB treatment completion. We reported the incidence and predictors of LTFU from TB treatment initiation during the 24 months of follow-up. LTFU was defined as having missed 4 consecutive monthly visits with the inability to make contact. Of the 642 patients randomized, a total of 96 (15.0%) were LTFU at a median of 6.0 [interquartile range (IQR), 1.1-11.3] months after TB treatment initiation. Incidence rates of LTFU were 7.5 per 100 person-years (PY) [95% confidence interval (CI): 4.9 to 11], 10.9 per 100 PY (95% CI: 7.6 to 15.1), and 11.0 per 100 PY (95% CI: 7.6 to 15.4) in the early integrated, late-integrated, and delayed treatment arms (P = 0.313). Incidence rate of LTFU before and after ART initiation was 31.7 per 100 PY (95% CI: 11.6 to 69.0) vs. 6.1 per 100 PY (95% CI: 3.7 to 9.4); incidence rate ratio (IRR) was 5.2 (95% CI: 2.1 to 13.0; P < 0.001) in the early integrated arm; 31.9 per 100 PY (95% CI: 20.4 to 47.5) vs. 4.7 per 10 PY (95% CI: 2.4 to 8.2) and IRR was 6.8 (95% CI: 3.4 to 13.6; P < 0.0001) in the late-integrated arm; and 21.9 per 100 PY (95% CI: 14.6 to 31.5) vs. 2.8 per 100 PY (95% CI: 0.9 to 6.6) and IRR was 7.7 (95% CI: 3.0 to 19.9; P < 0.0001) in the sequential arm. LTFU rates were not significantly different between the 3 trials arms. However, ART initiation within each trial arm resulted in a significant reduction in LTFU rates among TB patients.