A stepped-wedge randomised trial on the impact of early ART initiation on HIV-patients' economic outcomes in Eswatini

Abstract

Background: Since 2015, the World Health Organisation (WHO) recommends immediate initiation of antiretroviral therapy (ART) for all HIV-positive patients. Epidemiological evidence points to important health benefits of immediate ART initiation; however, the policy’s impact on the economic aspects of patients' lives remains unknown.

Methods: We conducted a stepped-wedge cluster-randomised controlled trial in Eswatini to determine the causal impact of immediate ART initiation on patients’ individual- and household-level economic outcomes. Fourteen healthcare facilities were non-randomly matched into pairs and then randomly allocated to transition from the standard of care (ART eligibility at CD4 counts of <350 cells/mm3 until September 2016 and <500 cells/mm3 thereafter) to the ‘Early Initiation of ART for All’ (EAAA) intervention at one of seven timepoints. Patients, healthcare personnel, and outcome assessors remained unblinded. Data were collected via standardised paper-based surveys with HIV-positive adults who were neither pregnant nor breastfeeding. Outcomes were patients’ time use, employment status, household expenditures, and household living standards.

Results: A total sample of 3019 participants were interviewed over the duration of the study. The mean number of participants approached at each facility per time step varied from 4 to 112 participants. Using mixed-effects negative binomial regressions accounting for time trends and clustering at the level of the healthcare facility, we found no significant difference between study arms for any economic outcome. Specifically, the EAAA intervention had no significant effect on non-resting time use (RR = 1.00 [CI: 0.96, 1.05, p=0.93]) or income-generating time use (RR = 0.94, [CI: 0.73,1.20, p=0.61]). Employment and household expenditures decreased slightly but not significantly in the EAAA group, with risk ratios of 0.93 [CI: 0.82, 1.04, p=0.21] and 0.92 [CI: 0.79, 1.06, p=0.26], respectively. We also found no significant treatment effect on households’ asset ownership and living standards (RR = 0.96, [CI 0.92, 1.00, p=0.253]). Lastly, there was no evidence of heterogeneity in effect estimates by patients’ sex, age, education, timing of HIV diagnosis and ART initiation.

Conclusions: Our findings do not provide evidence that should discourage further investments into scaling up immediate ART for all HIV patients.

Funding: Funded by the Dutch Postcode Lottery in the Netherlands, Alexander von Humboldt-Stiftung (Humboldt-Stiftung), the Embassy of the Kingdom of the Netherlands in South Africa/Mozambique, British Columbia Centre of Excellence in Canada, Doctors Without Borders (MSF USA), National Center for Advancing Translational Sciences of the National Institutes of Health and Joachim Herz Foundation.

Clinical trial number: NCT02909218 and NCT03789448.

Keywords: HIV/AIDS; antiretroviral treatment; epidemiology; global health; health economics; healthcare expenditures; medicine; randomized controlled trial; virus.

Conflict of interest statement

JS, SK, KM, FW, EM, CL, CW, AH, OO, SV, JD, SM, VO, TB, PG No competing interests declared

© 2020, Steinert et al.

Figures

Figure 1.. Participant flow chart (full sample).

Figure 2.. The causal effect of early ART initiation on economic outcomes.

Notes: Relative Risk presented for negative binomial mixed-effect regression with random intercept by healthcare facility (cluster) and a fixed effect for study period (Hussey and Hughes, 2007). All models control for respondent sex, age, marital status, and highest grade completed and were grand-mean centered. Parametric p-value obtained directly from the regression output; non-parametric p-value obtained from a permutation test with 1000 replications.

Figure 2—figure supplement 1.. Histogram: non-resting time use.

Figure 2—figure supplement 2.. Histogram: income-generating time use.

Figure 2—figure supplement 3.. Histogram: household expenditures.

Figure 2—figure supplement 4.. Household assets/living standards.

Figure 2—figure supplement 5.. Heterogeneity plots for non-resting time use.

Figure 2—figure supplement 6.. Heterogeneity plots for income-generating time.

Figure 2—figure supplement 7.. Heterogeneity plots for employment.

Figure 2—figure supplement 8.. Heterogeneity plots for household expenditures.

Figure 2—figure supplement 9.. Heterogeneity plots for household assets.

Figure 3.. Average adjusted predictions of employment rates by period and study arm.

Notes: Percent employed are the average adjusted predictions based on a logistic regression model with a time period fixed effect and a clinic-level random effect, interacting study period with trial arm, and controlling for patients’ age, sex, marital status, level of education, sex (binary), marital status (binary), and their level of education (continuous, specifying the highest grade completed). Period 0 and 7 are not shown because all participants interviewed in period 0 were part of the control phase and all participants interviewed in the last period were exposed to the intervention. The national total labour force participation rate is based on World Bank data and captures the proportion of the population of working age that is economically active during the reference period of 1 year.

Figure 4.. Map of the healthcare facilities that participated in the study.