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

Abstract

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 vs 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.

Results: Compared with the base-case scenario, leaving behind neither FSW nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 14.9 (10.4, 18.4)% vs 26.3 (19.7, 33.0)% if both were left behind-a 73 (40, 149)% increase. The effect of lower cascade on additional infections was larger for clients vs FSW, and both effects increased with population size and relative HIV incidence.

Conclusions: 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.

Keywords: HIV; antiretroviral therapy; healthcare disparities; mathematical model; sex work.

Figure 1:

Model structure and transitions Low: lowest activity; Med: medium activity; LR/HR: lower/higher risk; FSW: female sex workers; Clients: of FSW; CD4: CD4+ T-cell count per mm³; ART: antiretroviral therapy; rates—λ: force of infection; η: HIV progression; δ: diagnosis; τ: ART initiation; σ: viral suppression; σ′: viral re-suppression; ς: ART failure / discontinuation; not shown: turnover amongst activity groups in (a).

Figure 2:

Relative additional infections under counterfactual scenarios vs the base case Base case: 95–95-95 by 2020; counterfactual scenarios: 80–80-90 overall by 2020, with reduced cascade (60–40-80: left behind) among FSW, clients of FSW, both, or neither; whiskers, boxes, and midlines: 95% CI, 50% CI, median of model fits.

Figure 3:

Estimated effects on relative additional infections of disproportionate viral non-suppression (d) among FSW and clients vs population overall, plus effect modification by epidemic conditions (a) cumulative additional infections, (b) additional incidence rate by 2030 vs base case; FSW: female sex workers; Clients: of FSW; IR: incidence ratio in 2020; d_i: difference in subpopulation-i-specific viral non-suppression vs population overall within counterfactual scenario; points and error bars: mean and 95% CI for each effect estimated via Eq. (2).