Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability
In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes.
In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART.
At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable.
In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions.
- World Health Organization: Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Progress report 2010 2010. Accessed September 15, 2012, at http://whqlibdoc.who.int/publications/2010/9789241500395_eng.pdf
- Matovu JK, Makumbi FE: Expanding access to voluntary HIV counselling and testing in sub-Saharan Africa: alternative approaches for improving uptake, 2001–2007. Trop Med Int Health 2007, 12:1315–1322. CrossRef
- Muhamadi L, Xavier N, Mbona TN, Wabwire-Mangen F, Anna-Mia E, Stefan P, George P: Inadequate pre-antiretroviral care, stock-out of antiretroviral drugs and stigma: Policy challenges/bottlenecks to the new WHO recommendations for earlier initiation of antiretroviral therapy (CD < 350 cells/muL) in eastern Uganda. Health Policy 2010, 97:187–194. CrossRef
- Posse M, Meheus F, van Asten H, van der Ven A, Baltussen R: Barriers to access to antiretroviral treatment in developing countries: a review. Trop Med Int Health 2008, 13:904–913. CrossRef
- Wasswa H: Ugandan hospitals ration AIDS treatment as antiretrovirals start to run out. BMJ 2010, 341:c3900. CrossRef
- World Health Organization: Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2010 revision 2010. Accessed September 15, 2012, at http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf
- Kates J, Boortz K, Lief E, Avila C, Gobet B: Financing the response to AIDS in low- and middle-income countries: International assistance from the G8, European Commission and other donor governments in 2009. 2010. Accessed September 15, 2012, at http://www.kff.org/hivaids/upload/7347-052.pdf
- Anglaret X, Chene G, Attia A, Touré S, Lafont S, Combe P, Manlan K, N’Dri-Yoman T, Salamon R: Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d’Ivoire: a randomised trial Cotrimo-CI Study Group. Lancet 1999, 353:1463–1468. CrossRef
- Minga A, Danel C, Abo Y, Dohoun L, Bonard D, Coulibaly A, Duvignac J, Dabis F, Salamon R, Anglaret X: Progression to WHO criteria for antiretroviral therapy in a 7-year cohort of adult HIV-1 seroconverters in Abidjan, Côte d’Ivoire. Bull World Health Organ 2007, 85:116–123. CrossRef
- Seyler C, Messou E, Gabillard D, Inwoley A, Alioum A, Anglaret X: Morbidity before and after HAART initiation in Sub-Saharan African HIV-infected adults: a recurrent event analysis. AIDS Res Hum Retroviruses 2007, 23:1338–1347. CrossRef
- Goldie SJ, Yazdanpanah Y, Losina E, Weinstein MC, Anglaret X, Walensky RP, Hsu HE, Kimmel A, Holmes C, Kaplan JE, Freedberg KA: Cost-effectiveness of HIV treatment in resource-poor settings–the case of Côte d’Ivoire. N Engl J Med 2006, 355:1141–1153. CrossRef
- Walensky RP, Weinstein MC, Yazdanpanah Y, Losina E, Mercincavage LM, Touré S, Divi N, Anglaret X, Goldie SJ, Freedberg KA: HIV drug resistance surveillance for prioritizing treatment in resource-limited settings. AIDS 2007, 21:973–982. CrossRef
- Kimmel AD, Weinstein MC, Anglaret X, Goldie SJ, Losina E, Yazdanpanah Y, Messou E, Cotich KL, Walensky RP, Freedberg KA: Laboratory monitoring to guide switching antiretroviral therapy in resource-limited settings: clinical benefits and cost-effectiveness. J Acquir Immune Defic Syndr 2010, 54:258–268. CrossRef
- Losina E, Touré H, Uhler LM, Anglaret X, Paltiel AD, Balestre E, Walensky RP, Messou E, Weinstein MC, Dabis F, Freedberg KA: Cost-effectiveness of preventing loss to follow-up in HIV treatment programs: a Côte d’Ivoire appraisal. PLoS Med 2009, 6:e1000173. CrossRef
- Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Saah AJ, Detels R, et al.: Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997, 126:946–954.
- Grabar S, Le Moing V, Goujard C, Leport C, Kazatchkine MD, Costagliola D, Weiss L: Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 2000, 133:401–410.
- Losina E, Yazdanpanah Y, Deuffic-Burban S, Wang B, Wolf LL, Messou E, Gabillard D, Seyler C, Freedberg KA, Anglaret X: The independent effect of highly active antiretroviral therapy on severe opportunistic disease incidence and mortality in HIV-infected adults in Côte d’Ivoire. Antivir Ther 2007, 12:543–551.
- Touré S, Kouadio B, Seyler C, Traore M, Dakoury-Dogbo N, Duvignac J, Diakite N, Karcher S, Grundmann C, Marlink R, et al.: Rapid scaling-up of antiretroviral therapy in 10,000 adults in Côte d’Ivoire: 2-year outcomes and determinants. AIDS 2008, 22:873–882. CrossRef
- Seyler C, Anglaret X, Dakoury-Dogbo N, Messou E, Touré S, Danel C, Diakite N, Daudie A, Inwoley A, Maurice C, et al.: Medium-term survival, morbidity and immunovirological evolution in HIV-infected adults receiving antiretroviral therapy, Abidjan, Côte d’Ivoire. Antivir Ther 2003, 8:385–393.
- El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, et al.: CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006, 355:2283–2296. CrossRef
- Lopez AD: World Health Organization: World mortality in 2000: life tables for 191 countries. World Health Organization, Geneva; 2002.
- Messou E, Kouakou M, Gabillard D, Gouessé P, Koné M, Tchehy T, Losina E, Freedberg KA, Anzian A, Toure S, Anglaret X: Medication possession ratio: predicting and decreasing loss to follow-up in antiretroviral treatment programs in Côte d’Ivoire. J Acquir Immune Defic Syndr 2011,57(Suppl 1):S34-S39. CrossRef
- Stover J, Johnson P, Zaba B, Zwahlen M, Dabis F, Ekpini RE: The Spectrum projection package: improvements in estimating mortality, ART needs, PMTCT impact and uncertainty bounds. Sex Transm Infect 2008,84(Suppl 1):i24-i30. CrossRef
- UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance: Epidemiological fact sheets on HIV and AIDS. core data on epidemiology and response. Côte d’Ivoire; 2008. update. 2008. Accessed September 15, 2012, at http://apps.who.int/globalatlas/predefinedReports/EFS2008/full/EFS2008_CI.pdf
- World Health Organization: Antiretroviral therapy for HIV infection in adults and adolescents in resource-limited settings: towards universal access. Recommendations for a public health approach. 2006 revision 2006. Accessed September 15, 2012, at http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf
- Boulle A, Bock P, Osler M, Cohen K, Channing L, Hilderbrand K, Mothibi E, Zweigenthal V, Slingers N, Cloete K, Abdullah F: Antiretroviral therapy and early mortality in South Africa. Bull World Health Organ 2008, 86:678–687. CrossRef
- Ajose O, Mookerjee S, Mills EJ, Boulle A, Ford N: Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. AIDS 2012, 26:929–938. CrossRef
- Kantor R, Diero L, Delong A, Kamle L, Muyonga S, Mambo F, Walumbe E, Emonyi W, Chan P, Carter EJ, et al.: Misclassification of first-line antiretroviral treatment failure based on immunological monitoring of HIV infection in resource-limited settings. Clin Infect Dis 2009, 49:454–462. CrossRef
- Goddard M, Hauck K, Smith PC: Priority setting in health - a political economy perspective. Health Econ Policy Law 2006, 1:79–90. CrossRef
- McCaughey D, Bruning NS: Rationality versus reality: the challenges of evidence-based decision making for health policy makers. Implement Sci 2010, 5:39. CrossRef
- Robinson R: Limits to rationality: economics, economists and priority setting. Health Policy 1999, 49:13–26. CrossRef
- Mechanic D: Muddling through elegantly: finding the proper balance in rationing. Health Aff (Millwood) 1997, 16:83–92. CrossRef
- Mechanic D: Managed care and the imperative for a new professional ethic. Health Aff (Millwood) 2000, 19:100–111. CrossRef
- Ham C, Coulter A: Explicit and implicit rationing: taking responsibility and avoiding blame for health care choices. J Health Serv Res Policy 2001, 6:163–169. CrossRef
- Fox MP, Rosen S: Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review. Trop Med Int Health 2010,15(Suppl 1):1–15. CrossRef
- Laurent C, Diakhate N, Gueye NF, Toure MA, Sow PS, Faye MA, Gueye M, Laniece I, Toure Kane C, Liegeois F, et al.: The Senegalese government’s highly active antiretroviral therapy initiative: an 18-month follow-up study. AIDS 2002, 16:1363–1370. CrossRef
- Laurent C, Kouanfack C, Koulla-Shiro S, Nkoue N, Bourgeois A, Calmy A, Lactuock B, Nzeusseu V, Mougnutou R, Peytavin G, et al.: Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial. Lancet 2004, 364:29–34. CrossRef
- Hammond R, Harry TC: Efficacy of antiretroviral therapy in Africa: effect on immunological and virological outcome measures – a meta-analysis. Int J STD AIDS 2008, 19:291–296. CrossRef
- Moszynski P: Global Fund suspends new projects until 2014 because of lack of funding. BMJ 2011, 343:d7755. CrossRef
- UNAIDS/WHO: AIDS epidemic update. 2009. Accessed September 15, 2009, at http://data.unaids.org/pub/Report/2009/JC1700_Epi_Update_2009_en.pdf
- Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, et al.: Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011, 365:493–505. CrossRef
- Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, McIntyre J, Lingappa JR, Celum C: Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010, 375:2092–2098. CrossRef
- Keiser O, Anastos K, Schechter M, Balestre E, Myer L, Boulle A, Bangsberg D, Toure H, Braitstein P, Sprinz E, et al.: Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America. Trop Med Int Health 2008, 13:870–879. CrossRef
- Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Cost Effectiveness and Resource Allocation
- Online Date
- September 2012
- Online ISSN
- BioMed Central
- Additional Links
- Antiretroviral therapy
- Population health
- Limited resources
- Author Affiliations
- 1. Department of Healthcare Policy and Research, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA
- 2. Weill Cornell Medical College, New York, USA
- 3. Harvard School of Public Health, Boston, USA
- 5. INSERM Unité 897, Centre de Recherche “Epidémiologie et Biostatistique” and Université Victor Segalen Bordeaux 2, Bordeaux, France
- 6. Programme PAC-CI, Abidjan, Côte d’Ivoire
- 7. Massachusetts General Hospital, Boston, USA
- 4. Harvard Medical School, Boston, USA