Quantifying the impact of cascade inequalities: a modelling study on the prevention impacts of antiretroviral therapy scale-up in Eswatini.

BACKGROUND: Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95-95-95 targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate additional HIV infections expected in Eswatini if cascade scale-up had not been equal, and under which epidemic conditions these inequalities could have the largest influence.

METHODS: Drawing on population-level and FSW-specific surveys in Eswatini, we developed a compartmental model of heterosexual HIV transmission which included eight subpopulations and four sexual partnership types. We calibrated the model to stratified HIV prevalence, incidence, and ART cascade data. Taking observed cascade scale-up in Eswatini as the base-case - reaching 95-95-95 in the overall population by 2020 - we defined four counterfactual scenarios in which the population overall reached 80-80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60-40-80. We quantified relative additional cumulative HIV infections by 2030 in counterfactual base-case scenarios. We further estimated linear effects of viral suppression gap among FSW and clients on additional infections by 2030, plus effect modification by FSW/client population sizes, rates of turnover, and HIV prevalence ratios.

FINDINGS: Compared with the base-case scenario, leaving behind neither FSW and nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 13.3 (9.2, 18.7)% vs 26.7 (19.7, 33.8)% if both were left behind - a 104 (50, 167)% increase. The effect of lower cascade on additional infections was larger for clients FSW, and client population size, turnover, and prevalence ratios were the largest modifiers of both effects.

INTERPRETATION: Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade, particularly those that intersect with high transmission risk, could maximize incidence reductions from cascade scale-up.

FUNDING: Natural Sciences and Engineering Research Council of Canada; Ontario Ministry of Colleges and Universities; Canadian Institutes of Health Research; National Institute of Allergy and Infectious Diseases.