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The cost effectiveness of antiretroviral treatment strategies in resource-limited settings
Global Health Sciences Literature Digest
Published July 13, 2007
Journal Article

Bishai D, Colchero A, Durack DT. The cost effectiveness of antiretroviral treatment strategies in resource-limited settings. AIDS 2007 Jun;21(10):1333-40


To assess the cost-effectiveness of antiretroviral therapy (ART), comparing a reference strategy of no treatment to ART with four types of disease-monitoring strategies, with and without access to second-line treatment regimens.

Study Design

A computer-based discrete event simulation of HIV disease was developed for a cohort of 10,000 virtual patients. The course of each individual patient's disease status, reflected by CD4 cell counts, viral load, WHO stage (I-IV), and likelihood of death, was updated every six months as a succession of draws from an array of state-contingent statistical distributions. The model was calibrated to reflect the evolution of disease before and after ART initiation, using parameters from clinical studies. The different monitoring strategies included the following: a. syndromic management without laboratory tests ("ART ONLY"); b. syndromic management plus total lymphocyte counts every six months (TLC); c. syndromic management plus CD4 cell count assessment every six months (CD4); d. syndromic management plus CD4 cell count every six months and viral load assessment four weeks after the initiation of treatment, then every six months thereafter (VL). Cost estimates included $1 per TLC test, $5 ($1-$50 in sensitivity analyses) per CD4 test, $25 ($1-$25) per VL test, first-line ART $200 ($100 to $1,000) per year, second-line ART $900 ($400 to $1,400) per year, $150 per year for stage IV hospital costs, and $325 for switching to second-line ART.


The model was created using cost estimates from sub-Saharan African countries.


The study included 10,000 simulated patients. Starting at time 0, all patients began to visit the clinic every six months for ten years, or until death. It was assumed that all clinicians in a health system would be fully adherent to assigned guidelines, and that all patients were naive to previous ART. Patients were assumed to be as adherent to their treatment as were the cohorts that generated the clinical outcome parameters on which the model was based.


The ART ONLY strategy refers to an ART program in which clinicians had access only to HIV serology, hemoglobin, and the WHO clinical stage determined by history and physical examination. In the TLC strategy, clinicians had HIV serology and clinical staging, plus total lymphocyte count assays every six months. In the CD4 strategy, clinicians had access to all of the above, as well as CD4 cell counts every six months. Finally, in the VL strategy, clinicians had access to all of the above, plus viral load assays every six months (as well as four weeks after treatment initiation), to assess virological failure. In each strategy except VL, clinicians were kept blinded to one or more pieces of information known to the modeler. Treatment-switching decisions were based on laboratory monitoring.

Primary Outcomes

Outcomes were assessed over a ten-year horizon as life-years, quality-adjusted life-years (QALYs), and costs from the societal perspective discounted at 3%. External effects of patients' health behavior or health condition on outsiders were not considered.


The theoretical maximum number of discounted QALYs that 10,000 people in perfect health could accrue in 10 years is 87,861. Without treatment for HIV/AIDS, the model of natural history predicted that a population infected on average 7.5 years ago would experience 22,676 QALYs at a cost of $1.3 million, and 9,271 of the 10,000 would die during the subsequent decade. With ART, the number of deaths could be reduced to 2,311-2,714 in the same population, depending on the clinical strategy, and the population could more than double their QALY expectancy to between 45,717 and 47,637 discounted QALYs. The use of ART ONLY with no second line therapy (the least costly option) generates 45,736 discounted QALYs and 2,714 deaths, with discounted costs of $15.8 million over the decade. The median incremental cost-effectiveness ratio (ICER) for introducing ART ONLY (compared with no ART) is $628 without second-line treatment and $684 with second-line treatment. Without second-line treatment available, an average of 900 additional QALYs could be gained by adopting the CD4 cell count testing, at an additional cost of $221,000 or a median ICER of $238. With second line treatment, the CD4 strategy yields 1,380 additional QALYs, at an additional cost of $7.9 million and median ICER of $8,636. Any decision to advance to a TLC strategy would be dominated by the CD4 strategy without second-line therapy, and the median ICER with second-line treatment is $1,117. The median ICER value for a VL strategy is $16,139 when second-line treatment is unavailable and $14,670 with second-line ART available. Using mean values for the CD4 algorithm to assess the cost of second-line treatment independently of the choice of laboratory monitoring, an additional QALY would cost $19,147.


The authors conclude that, in the absence of second-line ART, the CD4 strategy is a more cost-effective laboratory strategy for managing HIV infection than either TLC or VL. In the presence of costly second-line treatments, CD4 cell count and viral load tests would enhance the appropriate selection of cases for second-line treatment, resulting in higher utilization of second-line treatment, more lives saved, and substantially higher costs unless the cost of second-line treatment falls dramatically.

Quality Rating

There is no formal rating system for cost-effectiveness studies such as this one; however, all cost-effectiveness studies are limited by the model assumptions and the accuracy of the data inputs. This study was limited because the model failed to consider the overall effects of ART on transmission and the quality of preventative counseling, laboratory monitoring, and consistency of patient adherence. It does include extensive sensitivity analysis to address variations in data inputs.

In Context

The estimated cost-effectiveness of first-line treatment with no monitoring in this study, $626-630/QALY gained, is close to a prior estimate of $547 per disability-adjusted life-year averted, despite the use of different methodologiesi. Another recent study estimated a cost of $620 per life-year gained obtained from ART plus opportunistic infection (OI) prophylaxis without CD4 cell count testing, compared with OI prophylaxis alone in a model calibrated to data from a cohort in Côte d'Ivoire.ii The model in this study predicted a cost of $380 per discounted life-year gained, comparing ART only with no second-line treatment with no ART. The differences may be explained by poorer effectiveness of first-line treatment in the Ivorian model, lack of OI prophylaxis in this model, and different assumptions about the efficiency with which failing patients are detected and switched to second-line treatment.

Programmatic Implications

This study indicates the cost-effectiveness of CD4 cell count testing in managing HIV infection in resource-limited settings. In the absence of second-line treatments, investments in CD4 testing capability can offset their costs by restraining the use of therapy in patients who do not need it. In the presence of costly second-line treatments, CD4 cell count and VL tests can enhance the appropriate selection of cases for second-line treatment, resulting in higher utilization of second-line treatment, more lives saved, and substantially higher costs unless the cost of second-line treatment falls dramatically. The data presented in this study should be useful to payers and policymakers in choosing among the potential treatment strategies. Additionally, this study highlights the impact of high prices of second-line ART and VL testing on lives saved. Great cost reductions for first-line ART and CD4 testing have been achieved in recent years through the use of generic formulations, country-specific pricing, and other negotiations. Similar reductions in the costs of second-line ART and VL testing will be critical for expansion of treatment in resource-limited settings, especially as the prevalence of resistance to first-line therapy rises.


  1. Hogan DR, Baltussen R, Hayashi C, Lauer JA, Salomon JA. Cost effectiveness analysis of strategies to combat HIV/AIDS in developing countries. BMJ 2005 Dec 17;331(7530):1431-7.
  2. Goldie SJ, Yazdanpanah Y, Losina E, Weinstein MC, Anglaret X, Walensky RP, et al. Cost-effectiveness of HIV treatment in resource-poor settings--the case of Côte d'Ivoire. N Engl J Med 2006 Sep 14;355(11):1141-53.