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The cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia
Global Health Sciences Literature Digest
Published June 19, 2008
Journal Article

Ryan M, Griffin S, Chitah B, Walker AS, Mulenga V, Kalolo D, et al. The cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia. AIDS 2008;22:749-57.

Objective

To measure the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia.

Study Design and Setting

Probabilistic models (decision analysis and semi-Markov model) using data from a randomized, double-blinded, placebo-controlled trial of the effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia.

Participants

Five hundred thirty-four children infected with HIV after infancy, aged 1-14 years and median at start of trial 4.5 years, were participants in the Children with HIV Antibiotic Prophylaxis (CHAP) trial in Zambia.

Outcomes

Cost per year of life saved, per quality adjusted life-years (QALYs), and per disability adjusted life-years (DALYs).

Methods

A decision-analysis model was structured around CD4 cell percentages (CD4%) as the marker of immunologic state at the onset of the study and as the marker of disease progression, assuming lifetime prophylaxis without decreasing efficacy of cotrimoxazole. A semi-Markov model was used to allow transition between levels of CD4% (16% and above, 8%-15%, and 7% and lower) and run for 20 years, a time period chosen to ensure that the entire cohort would have died at the end of the analysis. Probabilistic sensitivity analyses were used to determine if cotrimoxazole is cost-effective conditional on a threshold value for an additional year of life (QALY, DALY) for HIV-infected children aged 1 year and over. The value is the gross domestic product per capita in Zambia, or US$1019, in 2006.

Costs were estimated from resource data that had been collected in the CHAP trial. Costs included patient-specific direct medical costs, such as dose and duration of treatment, number of days of inpatient treatment at the University Teaching Hospital (UTH) in Lusaka, Zambia, and number of outpatient visits to the local clinics and health centers. Costs that are part of the basic healthcare package were included and costs for procedures associated only with the study were excluded from analysis. Information on healthcare costs came from the Ministry of Health and from the UTH. Costs for each health state, as determined by the three levels of CD4%, were assigned by taking the costs of care in the 12 weeks before and after each CD4 measurement, which was done every 24 weeks.

Utility and disability weights based upon a scale in which death is equal to zero and full health is equal to one have not been developed for HIV-infected children. The authors therefore used estimates from studies of adults in high-income countries (0.702)(1) that were comparable to the utility value from a single study of AIDS patients in South Africa prior to antiretroviral therapy (ART).(2)

Costs and outcomes were discounted by 3%, and routine hematology costs were not included in the base state because they are not included in WHO recommendations. Inputs were entered into the model as appropriated distributions. Sensitivity analyses were conducted to assess the effect of uncertainty from sources other than the input parameters.

Results

The internal validity of the model was robust in that the projected survival was within 10% of the actual survival of participants in the CHAP trial (4.4 years). Children with the highest CD4% (≥16%) had the lowest inpatient and outpatient costs (P<0.05), and those with CD4% between 8 and 15 had lower inpatient costs than the group with the lowest CD4%, but the two groups had similar costs for outpatient visits. Older children and those on cotrimoxazole had lower costs. The incremental cost-effectiveness ratio (ICER) per year of life saved was US$72, per QALYs was US%94, and per DALY was US$53. The costs associated with providing cotrimoxazole at local clinics rather than UTH produced lower ICERs.

Conclusion

Cotrimoxazole prophylaxis for HIV-infected children is very cost-effective. This result suggests the need for resource-constrained countries to adopt the WHO recommendations and provide cotrimoxazole prophylaxis as part of a basic healthcare plan.

Quality Rating

This study included every element listed in the Quality of Health Economic Studies (QHES) scale, indicating that it is of high quality.(3) The authors had a clear objective and appropriate inputs, weights, and models.

In Context

As this is the first cost-effectiveness analysis of cotrimoxazole among African children over 1 year of age, the results from this study cannot be compared directly with others. Findings from other cost-effectiveness analysis of cotrimoxazole prophylaxis in adults, however, also have shown that such treatment is cost-effective.

Programmatic Implications

Cotrimoxazole prophylaxis has been shown to reduce morbidity, hospital admissions, and mortality in HIV-infected adults and children in lower-income countries and in the absence of ART.(4,5,6) The WHO recommends cotrimoxazole prophylaxis for all HIV-infected adults and children who are symptomatic or, in the absence of symptoms, who are immunocompromised.(7) In spite of these recommendations, not all lower-income countries have adopted prophylaxis as part of routine HIV health care. The results from this outstanding study, combined with other cost-effectiveness analyses of cotrimoxazole prophylaxis, provide strong support for lower-income countries to prioritize the addition of prophylaxis into their basic medical care services for HIV-infected adults and children.

References

  1. Tengs TO, Lin TH. A meta-analysis of utility estimates for HIV/AIDS. Med Decis Making 2002;22(6):475-81.
  2. Hughes J, Jelsma J, Maclean E, Darder M, Tinise X. The health-related quality of life of people living with HIV/AIDS. Disabil Rehabil 2004;26(6):371-6.
  3. Ofman JJ, Sullivan SD, Neumann PJ, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. J Manag Care Pharm 2003;9(1):53-61.
  4. Chintu C, Bhat GJ, Walker AS, et al. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet 2004;364(9448):1865-71.
  5. Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d'Ivoire: a randomised controlled trial. Lancet 1999;353(9163):1469-75.
  6. Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353(9163):1463-8.
  7. WHO: Guidelines for cotrimoxazole prophylaxis for HIV-related infections among children, adolescents, and adults in resource limited settings, 2006.