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Cost-effectiveness of routine and low-cost CD4 T-cell count compared with WHO clinical staging of HIV to guide initiation of antiretroviral therapy in resource-limited settings
Global Health Sciences Literature Digest
Published October 18, 2010
Journal Article

Athan E, O'Brien DP, Legood R. Cost-effectiveness of routine and low-cost CD4 T-cell count compared with WHO clinical staging of HIV to guide initiation of antiretroviral therapy in resource-limited settings. AIDS. 2010;24:1887-1895.

In Context

Providing antiretroviral therapy (ART) in resource constrained areas is both feasible and cost-effective. While treatment initiation and monitoring in developed countries is done using CD4 cell counts, in countries lacking access to CD4 testing, the World Health Organization (WHO) clinical staging criteria are used for treatment guidance. Studies have found that clinical staging criteria are not reliable for screening.(1) Newer low-cost CD4 testing has similar sensitivity to conventional flow cytometry.


To compare the direct healthcare costs and benefits of using low cost or routine CD4 cell monitoring versus using WHO clinical staging criteria to guide initiation of ART.


Hypothetical sub-Saharan African area.

Study Design

Cost-effectiveness study using a Markov state transition model


A hypothetical cohort of 10,000 HIV-infected persons followed for 20 years.


Costs, years of life, and quality-adjusted life years (QALY)


The authors applied a Markov state transition probability model to a hypothetical cohort where all subjects began with a CD4 count of more than 350 cells/µl3. The model compares two clinical approaches to managing HIV; initiating all persons at CD4 counts under 200 cells/µl3 and the other in which all persons initiate ART at WHO clinical stages 3 or 4. The model uses costs, survival, and quality of life data obtained from studies of HIV natural history prior to ART that provide the means and 95% confidence intervals for the incubation time to AIDS or death.(2, 3, 4) The sensitivity of WHO criteria was taken from published studies using the CD4 count obtained from flow cytometry as the reference.(5)

In the model patients are assessed annually using the two criteria for initiating ART. The model allows for patients to improve clinically (e.g. CD4 > 350 cells/µl3) and to reenter the model as well as to receive ART but die within 90 days of initiating treatment. Estimates for these outcomes were obtained from published studies in resource-constrained areas.(6) Adverse treatment effects and poor adherence were also included in the models.

The costs and effects of opportunistic illnesses and HIV viral load testing were not included. Health care utilization and costs were obtained from primary data in sub Saharan settings.(6) In the sensitivity analysis the cost and effect of changing to a second-line regimen after 10 years were assessed.

Costs included ART, other healthcare services, monitoring adverse effects of therapy, first- and second-line medications and CD4 testing. In the base analysis future costs and outcomes were discounted 3% per year. The utility values for QALYs were obtained from published studies in South Africa and from EuroQol. The authors used the cost-effectiveness ration recommended by the Commission on macroeconomics and Health for the Cote d'Ivoire and Republic of South Africa. A sensitivity analysis was done to estimate uncertainty.


For the base analysis: the total costs and effects, in terms of life years and QALYs for individuals assessed by WHO clinical staging only for eligibility for ART, over 20 years, and applying a discount factor of 3%, were $8351, 10.32 and 9.08, respectively. With patients assessed by annual routine CD4 cell count testing, the costs, life years and QALYs were $8543, 10.54 and 9.29, respectively. The incremental cost effectiveness ratio was $884 per life year gained and $939 per QALY gained. When the low-cost CD4 cell test was used, the cost was $8368 and the incremental cost effectiveness ratio was $80 per life year gained and $85 per QALY gained.


Using low cost or routine CD4 cell monitoring to guide treatment in sub-Saharan Africa is cost-effective and should be included in HIV treatment programs.

Quality Rating

Based on the Quality of Health Economic Studies (QHES) tool, this was an excellent analysis. Its particular strengths include having an objective outcome with the perspective of the analysis stated clearly, well documented sources for variable estimates, sensitivity analysis for uncertainty, incremental analyses, sufficient follow-up time, appropriate costs, outcomes, and model. Limitations were addressed and conclusions were appropriate.

Programmatic Implications

This is an important study because it demonstrates the value in terms of both cost and benefit of using CD4 cell monitoring in the care of patients in resource constrained areas. Given the poor sensitivity of clinical monitoring and the availability of low cost and point of care CD4 testing as well as expansion of treatment programs in developing countries, CD4 cell counts should be used for determining the time to begin ART, monitor response, and change regimens.


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