Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project

Abstract

Background: The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision referrals increased coverage and decreased incidence over ∼29 months of follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population.

Setting: Rural and periurban communities in Botswana.

Methods: We used the Cost-Effectiveness of Preventing AIDS Complications model to estimate lifetime health impact and cost of (1) earlier ART initiation and (2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio [US$/quality-adjusted life-years (QALY)] for CP vs. standard of care.

Results: In CP, 1418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an incremental cost-effectiveness ratio of $79 per QALY.

Conclusions: Enhanced HIV testing, linkage, and early ART initiation improve life expectancy, reduce transmission, and can be cost-effective or cost-saving in settings like Botswana.

Trial registration: ClinicalTrials.gov NCT01965470.

Conflict of interest statement

The authors declare no conflicts of interest.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1.

Overview of methods and model structure: cost-effectiveness of the Botswana Combination Prevention Project (BCPP). This figure outlines the CEPAC model runs used in the cost-effectiveness analysis of the Botswana Combination Prevention Project. Prevalent cohort: The CP subcohort represents PWH who were detected and started on first-line ART during the BCPP trial. The counterfactual SOC represents PWH who were not detected or linked to care through the trial (they may be linked through standard of care testing). Discounted quality-adjusted life years and costs among prevalent PWH excluding the impact of transmissions (QALYCP/ QALYSOC and CostCP/CostSOC) are shown in blue. Primary transmissions from PWH in the prevalent cohort (TxCP/TxSOC) are shown in green. Incidence cohort: The Acute HIV Infection (AHI) subcohort represents participants who acquired HIV during the BCPP trial and the counterfactual Averted Infection (HIV−) represents participants who did not aquire HIV during the trial. Model outcomes include discounted quality-adjusted life years and costs (QALYAHI/QALYHIV− and CostAHI/CostHIV−) and are shown in grey. The lifetime difference in discounted quality-adjusted life-years and costs between the Acute HIV and Averted Infection cohorts represents the negative health impact (QALYTx) and additional costs (CostTx) per transmission. To determine prevalent model outcomes including transmission impact, we multiply the impact per transmission (QALYTx and CostTx) by the number of first order transmissions in the CP and SOC subcohorts. We add the product to the discounted quality-adjusted life years (QALYCP/ QALYSOC) and costs (CostCP/CostSOC) for each subcohort. Prevalent cohort outcomes including transmission impact are found in Table 2. CP, combination prevention; SOC, standard of care; PWH, people with HIV; ART, antiretroviral therapy; T0, time zero (model iniation); QALY, quality-adjusted life-years; Tx, transmission; AHI, acute HIV infection; HIV-, no HIV infection.

Figure 2.

Cost breakdown of the incremental cost of the CP intervention. This waterfall chart reports the positive and negative incremental costs (y-axis) of each component (x-axis) of the CP intervention arm compared to the standard of care arm. Positive incremental costs are represented in orange, negative incremental costs in blue, and total or net incremental costs in grey. Exact cost values appear above or below the corresponding bar. CP, combination prevention; SOC, standard of care; PWH, people with HIV; VMMC, voluntary male medical circumcision.

Figure 3.

One-way sensitivity analyses on the cost-effectiveness ($/QALY) of CP compared to SOC in Botswana, including the impact of first-order HIV transmissions over ten years. This tornado diagram represents the ICERs (x-axis) for CP compared to SOC after input parameters (y-axis) were varied. The base case value for each input parameter is listed in parentheses before the semi-colon. The range across which we varied each parameter is listed after the semi-colon, with the value resulting in the lowest ICER before the hyphen and the value resulting in the highest ICER after the hyphen. The range of ICERs for each varied parameter is indicated by the horizontal bars. Longer horizontal bars indicate parameters to which the model results are most sensitive. The solid black line indicates the ICER for CP vs. SOC in the base case ($79/QALY). The dotted black line indicates 0.25x Botswana’s per capita GDP in 2019. CP, combination prevention; SOC, standard of care; ART, antiretroviral therapy; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

Figure 4.

Two-way sensitivity analysis: Cost-effectiveness as a function of the incremental increase in ART coverage and the cost of the CP intervention. This heat map reports the ranges of incremental cost-effectiveness ratios of CP vs. SOC as a function of the two most influential parameters in Figure 3: incremental cost of the CP intervention (vertical axis) and incremental increase in ART coverage and infections averted (horizontal axis). Colors indicate the incremental cost-effectiveness ratio achieved by each combination of these parameters, ranging from very cost-effective in green (per capita GDP of $8,000) to cost-effective in yellow (0.25–0.5x GDP) and orange (0.5–1x GDP) and not cost-effective in red (>1x GDP). The base case combination (nine-percentage point incremental increase in ART coverage for an incremental CP cost of $1.7 million) is indicated by the ** in the upper left cell. CP, combination prevention; SOC, standard of care; ART, antiretroviral therapy; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; GDP, gross domestic product.