Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

<div><h3>Background</h3><p>We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ).</p> <h3>Methods</h3><p>We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years.</p> <h3>Results</h3><p>The program cost $69.7 million for 125,436 person-years of ART, or$556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector.</p> <h3>Conclusions and Significance</h3><p>The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.</p> </div

One-way sensitivity analysis.

1<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051993#pone-0051993-t001" target="_blank">Table 1</a> for switch rate per year per successive year of treatment.</p><p>Cost per DALY averted when six key model input variables are varied to 50% and 150% of base case values.</p

Estimated regressions of average total cost per DALY averted of antiretroviral therapy in 45 facilities in Zambia.

<p>Note: **p<0.05,</p>*<p>p<0.1,+p<0.2. p-values are given in parentheses to the right of the coefficients in columns (1), (2) and (4).</p>c<p>Values of p for “Early Start” are the significance level at which the joint hypothesis can be rejected that neither baseline CD4 nor proportion of patients initiating at WHO stage IV influences the dependent variable.</p

Bivariate analysis of association between average total cost and its components and eight explanatory variables.

<p>Column definitions:</p><p>(1) Variable definitions.</p><p>(2) Specifies whether variable is continuous or discrete, and if discrete, the criterion used to define the dummy variable.</p><p>(3) Mean value of the explanatory variable over all 45 observations. For discrete versions of the variables, the mean is the proportion of observations for which D  = 1.</p><p>(4) Standard deviation of the explanatory variables.</p><p>(5) Correlation between a continuous explanatory variable and average total cost.</p><p>(6) Mean value of average total cost for values of the dummy variable equal to zero.</p><p>(7) Mean value of average total cost for values of the dummy variable equal to one.</p><p>(8) p-value of the test of the null hypothesis of no relationship between the explanatory variable and average total cost.</p><p>(9) – (12): Same definitions as (5) – (8), respectively, except for average on-site cost instead of average total cost.</p><p>(13) – (16): Same definitions as (5) – (8), respectively, except for average off-site cost instead of average total cost.</p

Breakdown of incremental ART program costs by major expenditure categories.

<p>Breakdown of incremental ART program costs by major expenditure categories.</p

Distribution of cost sub-components between total and on-site components.

<p>Distribution of cost sub-components between total and on-site components.</p

Estimated costs of ART service delivery per patient year by ART facility characteristic.

<p>Figure shows total and on-site costs. Author’s estimates constructed from the semilog specification in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051993#pone-0051993-t005" target="_blank">Table 5</a>. The “reference” facility is an urban public sector clinic with less than 91% adherence, less than 2 years’ experience, fewer than 300 patients, and late starting patients. Estimated effects of facility characteristics accumulate from left to right.</p

CIDRZ Zambia ART program cost-effectiveness in 45 sites.

<p>Cost effectiveness is presented as costs and mortality reductions following initial 16 weeks of therapy; and for the entire period between ART services initiation at each site and July 1, 2008. Means are the sum of all DALYs or deaths averted across all sites, divided by the sum of the costs at all sites. Standard deviations are calculated for the mean values of all sites.</p

CIDRZ ART services delivered and associated costs in 45 clinical sites in Zambia.

1<p>Excluding training and laboratory.</p>2<p>Refurbishment - renovation and imputed opportunity cost of space.</p>3<p>Adjusted for difference in % female clients between HBAC and CIDRZ cohorts.</p><p>Program phased in April 28, 2004–July, 15, 2007; data through July 1, 2008. All values derived from CIDRZ program records except Hazard ratio: Female - male and Deaths per 100 PY in HBAC comparison group (Mermin, 2008) and Discounted DALYS averted per death averted (Marseille, 2009). Annual regimen switch rates, death rates in the comparison group, DALYs per death averted and the discount rate are constant across sites but are varied from 50% to 150% in the sensitivity analyses.</p

Estimated regressions of average total and average on-site cost per patient-year of antiretroviral therapy in 45 facilities in Zambia.

<p>Note:**p<0.05,</p>*<p>p<0.1,+p<0.2. p-values are given in parentheses below the coefficients in columns (1) through (6).</p>a<p>Coefficients in columns (5) and (6) are estimated by Zellner’s seemingly unrelated regression method using Stata’s sureg command.</p>b<p>Predicted values in columns (7) and (8) are calculated from the coefficients in columns (5) and (6) respectively, as explained in the text.</p>c<p>Values of p for “Early Start” are the significance level at which the joint hypothesis can be rejected that neither baseline CD4 nor proportion of patients initiating at WHO stage IV influences the dependent variable. For the two equations estimated jointly (columns (5) and (6)) the p-value is the probability that these four estimated coefficients could occur if all four parameters were actually zero.</p