Clinical outcomes of HIV treatment clients enrolled in six-month dispensing after less than 6 months on treatment in Zambia: A target trial emulation

Abstract

Abstract Background Six-month multi-month dispensing (6MMD) of antiretroviral therapy (ART) reduces clinic visit frequency and is associated with improved retention in care. During the COVID-19 pandemic, Zambia offered 6MMD to clients ≥3 months after ART initiation, rather than the ≥6 months standard requirement. We estimated the effect of early (<6 months on ART) versus standard (6-12 months) 6MMD enrolment on rate of treatment interruption. Methods We emulated a target trial using routinely collected electronic medical records from 12 public health facilities in Zambia. Eligible clients were ≥15 years, initiated ART 01/20-08/22, were WHO stage 1 or 2 at ART initiation, and had ≥21 months of potential follow-up. Treatment interruption was defined as missing a scheduled clinic or pharmacy visit by >28 days. We applied a clone-censor-weight approach to reduce immortal time bias. Clones were censored when observed dispensing deviated from their assigned strategy. Inverse probability of censoring weights (IPCW) accounted for informative censoring, while inverse probability of treatment weights (IPTW) balanced measured baseline confounders between strategies. We used weighted pooled logistic regression of person-month data to estimate the odds of treatment interruption between early and standard 6MMD enrollers, including follow-up month to model the monthly baseline risk. Results 6,142 ART clients met inclusion criteria. 741 (12.1%) were early 6MMD enrollers, 1,590 (26.1%) standard 6MMD enrollers, and 3,811 (62.0%) eligible clients who never enrolled in 6MMD. During follow-up, 268 treatment interruptions occurred. In the primary analysis, early 6MMD was associated with lower odds of treatment interruption than standard 6MMD OR 0.701 (95% CI 0.51– 0.97). The predicted cumulative probability of treatment interruption at 18 months was 6.5% under the early 6MMD strategy and 9.1% under the standard strategy (risk difference: −2.6 percentage points). Conclusions Enrolment in 6MMD at 3-6 months after ART initiation was associated with lower odds of treatment interruption than standard enrolment at 6-12 months, with a predicted absolute risk difference of −2.6 percentage points at 18 months. We found no evidence that earlier access to 6MMD increases the risk of treatment interruption.