The past decade has seen tremendous progress in the delivery of treatment of HIV-infected individuals worldwide. Better antiretroviral therapy (ART), improved laboratory monitoring, and evidence of ART as prevention have led to the possibility of beginning to reverse the AIDS pandemic. At the same time, limited resources worldwide have tempered the ability of the international community to optimally utilize these proven interventions. In 2004 and in 2008, NIAID awarded our research group funding to develop and expand the Cost-Effectiveness of Preventing AIDS Complications International (CEPAC-I) Model, a computer simulation of the natural history, clinical management, outcomes, and cost-effectiveness of HIV treatment in 3 resource- limited settings: South Africa, C?te d'lvoire, and India. In the last 5-year cycle of the project, this collaboration produced more than 105 original papers in peer-reviewed journals. In this continuation, we propose to further expand the CEPAC-I Model to reflect important developments in HIV/AIDS, and to address several of the most pressing questions in HIV care. We have three specific aims:
Specific Aim 1 : To examine the optimal packages of HIV care - ART initiation, monitoring strategies including use of point-of-care tests, and regimen sequencing - given varying resource constraints in South Africa, C?te d'Ivoire, India, and Brazil. We will create a new web-based 'metamodel'structure to allow clinical policy makers in other countries to access the capabilities of the CEPAC-I Model.
Specific Aim 2 : To define the benchmarks of clinical efficacy and cost by which new technologies - including long-acting ART and strategies for HIV eradication - may become viable and cost-effective options. We will perform analyses to establish performance requirements for new HIV treatments in resource-limited settings to be cost-effective. Novel modeling methods will incorporate patient heterogeneity as well as expanded probabilistic sensitivity analysis.
Specific Aim 3 : To project clinical outcomes, cost, and cost-effectiveness of detection and treatment for major co-morbidities in people with HIV, including hepatitis B and C viruses, TB, and hypertension. We will assess the cost-effectiveness of merging HIV care with screening and treatment for other common diseases in people with HIV. With new approaches to costing and budget impact analysis, we will assess the affordability of broadening HIV treatment programs. The assembled internationally-recognized, multidisciplinary research team has a lengthy record of disseminating findings to inform HIV care and guidelines, both in the US and internationally. To expand the project scope, we have added investigators from Brazil, the most HIV-affected country in Latin America. By leveraging the team's progress over the past 9 years and accomplishing the aims above, the proposed studies will answer many critical HIV clinical and policy questions facing the global HIV community.

Public Health Relevance

With extraordinary progress in delivering HIV treatment and care in resource-limited settings over the past decade, there is now unprecedented opportunity to further improve outcomes and reverse the trajectory of the HIV/AIDS pandemic. The CEPAC-International Model provides a detailed and sophisticated modeling environment which is uniquely able to address the role of clinical interventions in HIV in the context of their broader public health implications and economic impact. This methodology allows investigation of problems from multiple directions in four countries representing different regions of the world and provides clear insight into proven as well as evolving approaches to HIV care.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS Clinical Studies and Epidemiology Study Section (ACE)
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Huebner, Robin E
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Massachusetts General Hospital
United States
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Luz, Paula M; Osher, Benjamin; Grinsztejn, Beatriz et al. (2018) The cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men and transgender women at high risk of HIV infection in Brazil. J Int AIDS Soc 21:e25096
Neilan, Anne M; Cohn, Jennifer E; Lemaire, Jean-Francois et al. (2018) HIV Testing After a First Positive Rapid Diagnostic Test: A Role for Nucleic Acid Testing? Open Forum Infect Dis 5:ofy170
Freedberg, Kenneth A; Kumarasamy, Nagalingeswaran; Borre, Ethan D et al. (2018) Clinical Benefits and Cost-Effectiveness of Laboratory Monitoring Strategies to Guide Antiretroviral Treatment Switching in India. AIDS Res Hum Retroviruses 34:486-497
Mallampati, Divya; MacLean, Rachel L; Shapiro, Roger et al. (2018) Optimal breastfeeding durations for HIV-exposed infants: the impact of maternal ART use, infant mortality and replacement feeding risk. J Int AIDS Soc 21:e25107
Zheng, Amy; Kumarasamy, Nagalingeswaran; Huang, Mingshu et al. (2018) The cost-effectiveness and budgetary impact of a dolutegravir-based regimen as first-line treatment of HIV infection in India. J Int AIDS Soc 21:e25085
Ahonkhai, Aimalohi A; Banigbe, Bolanle; Adeola, Juliet et al. (2018) High Medication Possession Ratios Associated With Greater Risk of Virologic Failure Among Youth Compared With Adults in a Nigerian Cohort. J Acquir Immune Defic Syndr 78:322-328
Kubiak, R W; Herbeck, J T; Coleman, S M et al. (2018) Urinary LAM grade, culture positivity, and mortality among HIV-infected South African out-patients. Int J Tuberc Lung Dis 22:1366-1373
Hermans, Sabine; Caldwell, Judy; Kaplan, Richard et al. (2017) The impact of the roll-out of rapid molecular diagnostic testing for tuberculosis on empirical treatment in Cape Town, South Africa. Bull World Health Organ 95:554-563
O'Laughlin, K N; Kasozi, J; Rabideau, D J et al. (2017) The cascade of HIV care among refugees and nationals in Nakivale Refugee Settlement in Uganda. HIV Med 18:513-518
Paltiel, A David; Zheng, Amy; Weinstein, Milton C et al. (2017) Setting Performance Standards for a Cost-Effective Human Immunodeficiency Virus Cure Strategy in South Africa. Open Forum Infect Dis 4:ofx081

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