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Based on data from West Africa, Elena Losina and colleagues predict that interventions to reduce dropout rates from HIV treatment programs (such as eliminating copayments) will be cost-effective., Background Data from HIV treatment programs in resource-limited settings show extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of antiretroviral therapy (ART) initiation. Our objective was to project the clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV care in West Africa. Methods and Findings We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International model to project the clinical benefits and cost-effectiveness of LTFU-prevention programs from a payer perspective. These programs include components such as eliminating ART co-payments, eliminating charges to patients for opportunistic infection-related drugs, improving personnel training, and providing meals and reimbursing for transportation for participants. The efficacies and costs of these interventions were extensively varied in sensitivity analyses. We used World Health Organization criteria of, Editors' Summary Background Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981. Currently, about 33 million people are infected with the human immunodeficiency virus (HIV), which causes AIDS. Two-thirds of people infected with HIV live in sub-Saharan Africa. HIV infects and destroys immune system cells, thereby weakening the immune system and rendering infected individuals susceptible to infection. There is no cure for HIV/AIDS. Combination antiretroviral therapy (ART), a mixture of antiretroviral drugs that suppress the replication of the virus in the body, is used to treat and prevent HIV infection. ART is expensive but major international efforts by governments, international organizations, and funding bodies have increased ART availability. According to World Health Organization (WHO) estimates, at least 9.7 million people in low- and middle-income countries need ART and as of 2007, 3 million of those people had reliable access to the drugs. Why Was This Study Done? Although ART is an effective treatment for HIV, a large number of individuals who initiate ART do not receive long-term follow-up care. These patients are generally sicker and have a worse long-term outcome than those who receive follow-up care. Loss to follow up (LTFU) is a significant problem that can undermine the benefits of expanding ART availability. Strategies to improve follow up concentrate on bringing lost patients back into the health care system, but such patients often die before they can be contacted. Prevention of LTFU might be a better strategy to improve HIV care after ART initiation, but there is little information available on which specific interventions might best accomplish this goal. What Did the Researchers Do and Find? Given the lack of reported data on the actual costs and effectiveness of LTFU prevention, the researchers used a model to estimate the clinical impact and cost-effectiveness of several possible strategies to prevent LTFU in HIV-infected persons receiving ART in Côte d'Ivoire, West Africa. The researchers used the previously developed Cost-Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model and combined it with data from a program of ART delivery in Abidjan, Côte d'Ivoire. They then projected the clinical benefits and the cost required to attain a given level of benefit (cost-effectiveness ratio) of different LTFU-prevention strategies from the perspective of the payer (the organization that pays all the medical costs to provide care). Several interventions were considered, including reducing costs to patients (eliminating patient co-payments and paying for transportation) and increasing services to patients at their visits (improving staff training in HIV care, and providing meals at clinic times). LTFU was predicted to cause a 54.3%–58.3% reduction in the estimated life expectancy beyond age 37; patients continuing HIV care were predicted to live a further 144.7 months whie those lost to follow up by 1 year after ART initiation were predicted to live only for a further 73.9–80.7 months. LTFU-prevention strategies in the Côte d'Ivoire were deemed to be cost-effective if they cost less than $2,823 (which is 3× gross domestic product per capita) per year of life saved. The efficacy and cost of the different LTFU-prevention strategies varied in the analyses; stopping ART co-payment alone would be cost-effective at a cost of $22/person/year if it reduced LTFU rates by 12%, while including all the LTFU-prevention strategies described would be cost-effective at $77/person/year if they reduced LTFU-rates by 41%. What Do These Findings Mean? The findings suggest that moderately effective strategies for preventing LTFU in resource-limited settings would improve survival, provide good value for money, and should be used to improve HIV treatment programs. Although modeling is valuable to explore the costs and effectiveness of LTFU-prevention strategies it cannot replace the need for more reported data to shed light on problems leading to LTFU and the prevention strategies required to combat it. Also, Côte d'Ivoire might not be representative of all West African countries or resource-limited settings. A similar analysis using data from other ART programs in different countries would be useful to provide better understanding of the impact of LTFU in HIV treatment programs. Finally, the research highlights the cost of second-line ART (a new antiretroviral drug combination for patients in whom first-line treatment fails) as a crucial issue. It is estimated that 5% of all people receiving ART in low- and middle-income countries receive second-line ART and these numbers are expected to increase. Second-line ART had major effects on cost-effectiveness, and a reduction in the cost of this treatment is critical in order to guarantee continued access to HIV treatment. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000173. This study is further discussed in a PLoS Medicine Perspective by Gregory Bisson and Jeffrey Stringer WHO provides information on disease prevention, treatment, and HIV/AIDS programs and projects The UN Millennium Development Goals project site contains information on worldwide efforts to halt the spread of HIV/AIDS aidsmap, a nonprofit, nongovernmental organization, provides information on HIV and supporting those living with HIV