Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

Abstract

Background: New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly.

Methods: We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the $/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia: $1425, India: $1489, Vietnam: $1407) and 'cost-effective' if $/DALY was less than three times per capita GDP.

Findings: In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from $237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to $749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to $241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective.

Interpretation: Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets.

Funding: The Bill and Melinda Gates Foundation and World Health Organization.

Figure 1

The incremental cost per DALY averted for expanding ART eligibility criteria to include HIV-positive adults with CD4 ≤500 cells/µL or all HIV-positive adults, assuming continuation of status quo patterns of healthcare access. Results calculated over a 20 year time horizon, with all costs and health benefits discounted at 3% per annum. All costs reported in 2012 US dollars. Horizontal dashed lines represent cost-effectiveness benchmarks of one times and three times per capita GDP. Menzies (South Africa) and models for India only simulated eligibility for all HIV-positive adults, not restricted to those with CD4 ≤500 cells/µL. ‘*’ indicates that eligibility for CD4 ≤500 cells/µL is dominated by eligibility for all HIV-positive adults. For the Goals model in Zambia, the estimated ICER is negative because over 20 years the strategy produces health benefits and is estimated to be cost saving over 20 years due to the reduced treatment and care burden, including savings due to averted TB treatment costs.

Figure 2

The projected annual HIV incidence rate per 100 person-years for ART eligibility (CD4 ≤350 cells/µL: solid; CD4 ≤500 cells/µL: dashed; all HIV-positive: dotted) and health access strategies (status quo: red; expanded access: blue). In the generalized epidemic settings (South Africa, Zambia), ‘expanded access’ refers to expanded access for the general population. In concentrated epidemic settings (India, Vietnam), ‘expanded access’ refers to expanded access for all high-risk groups (FSW, MSM, PWID; see Table 1).

Figure 3

The incremental costs for different ART eligibility and access strategies compared to continuation of 2010 eligibility guidelines and status quo access to care, summed over 20 years. Costs are undiscounted, and reported in 2012 US dollars. Costs underneath the horizontal axis represent cost savings. Total incremental costs are indicated by solid dots. Strategies are indicated by ‘eligibility, access’. In generalized epidemic settings (South Africa, Zambia), ‘expanded access’ refers to expanded access for the general population. In concentrated epidemic settings (India, Vietnam), ‘expanded access’ refers to expanded access for all high-risk groups (FSW, MSM, PWID; see Table 1). For South Africa and Zambia, within each strategy each bar represents a model in the same sequence as the bars in Figure 1. ‘x’ indicates that the CD4 ≤500 cells/µL strategy is not simulated by Menzies. The models for Belgaum and Vietnam also simulated expanded access to the general adult population, which are not illustrated (see Table 3 and Supplementary Information, Figures S5–S7 and Tables S9–S10).

Figure 4

Threshold analysis depicting the strategy associated with the lowest cost per DALY averted for given percentage change in the baseline cost assumed for pre-ART care (vertical axis) and for HIV diagnostic testing and linkage to care (horizontal axis). All strategies are compared to the baseline strategy assuming continuation of CD4 ≤350 cells/µL eligibility guidelines and status quo access to care. ‘x’ indicates the baseline cost estimated for pre-ART care and diagnostic and linkage to care (Table 2).