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After 2 years on antiretroviral therapy, survival in South African patients meets rates from North America

PLOS

Provided that therapy is started promptly, South Africans with HIV have chances of remaining alive beyond 2 years on antiretroviral therapy (ART) that are comparable to those of North American patients, according to new research in PLOS Medicine by Andrew Boulle of the University of Cape Town and colleagues.

The researchers compared survival data from 4 cohorts in South Africa (30,467 adults), 6 in North America (7,160 adults), and 9 in Europe (29,727 adults) in which individuals were followed for up to 4 years after starting ART. After correcting for under-ascertainment of mortality in patients who were lost to cohort follow up in South Africa through linkage to a population register, the researchers found that South African cohorts had higher mortality (9.7%, 95% confidence interval [CI]: 9.2%, 0.1%) than North American (4.6%, 95% CI: 4.0%, 0.1%) or European (2.0%, 95% CI: 1.8%𔃀.2%) cohorts after one year on treatment, possibly because the immune systems of South African patients had sustained more HIV-induced damage, as evidenced by lower CD4 T-cell counts, by the time patients started treatment.

However, between 2 and 4 years on ART, mortality rates in North America were comparable to or higher than those for South Africa. After statistical adjustment for differences in baseline characteristics such as gender and stage of HIV disease, the researchers estimated mortality rate ratios to be 0.46 (95% confidence interval [CI] 0.37.58) comparing Europe to South Africa, and 1.62 (95% CI 1.27.05) comparing North America to South Africa between 24 and 48 months on ART.

The authors note that factors affecting survival on ART differ between settings: "for example [hepatitis C] infection may impact later mortality in the North America cohorts in this study," while in South Africa "those accessing care may have been exceptionally motivated citizens, especially in the early years of the programs when treatment availability was more limited."

In an accompanying Perspective, Agnes Binagwaho of the Ministry of Health of Rwanda and colleagues, who were not involved in the research, discuss the implications of the study's results for people with HIV in both high- and low-income countries. The Perspective authors point out that "disparities of access and outcome that are both regional and intensely local in nature warrant a substantial increase in attention in each of the settings studied."

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Research Article

Funding of the International epidemiological Databases to Evaluate AIDS, Southern Africa (IeDEA-SA) collaboration was provided by the US National Institute of Allergy and Infectious Diseases (NIAID), grant no. 5U01AI069924-05. The ART Cohort Collaboration is funded by UK Medical Research Council grants and the Department for International Development (DFID), grants G0700820 and MR/J002380/1. Sources of funding of individual cohorts include the Agence Nationale de Recherche sur le SIDA et les he´patites virales (ANRS); the Institut National de la Sante´ et de la Recherche Me´dicale (INSERM); the French, Italian, and Spanish Ministries of Health; the Swiss National Science Foundation (grant 33CS30_134277); the Ministry of Science and Innovation and the Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006); the Stichting HIV Monitoring; the European Commission (EuroCoord grant 260694); the British Columbia and Alberta Governments; the National Institutes of Health (NIH): UW Center for AIDS Research (CFAR) (NIH grant P30 AI027757), UAB CFAR (NIH grant P30-AI027767), The Vanderbilt-Meharry CFAR (NIH grant P30 AI54999), National Institute on Alcohol Abuse and Alcoholism (U10-AA13566, U24-AA020794); the US Department of Veterans Affairs; the Michael Smith Foundation for Health Research; the Canadian Institutes of Health Research; the VHA Office of Research and Development; and unrestricted grants from Abbott, Gilead, Tibotec-Upjohn, ViiV Healthcare, MSD, GlaxoSmithKline, Pfizer, Bristol Myers Squibb, Roche, and Boehringer-Ingelheim. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests

MSS is the local principal investigator on studies sponsored by Abbvie, Gilead, BMS, Merck, BI, ViiV, and Jannsen, where funding goes directly to the institution but not to MSS. PR, through his institution, has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceutica N.V., Merck&Co, Bristol-Myers Squibb, and ViiV Healthcare, and travel support through his institution from Gilead Sciences and Janssen Pharmaceutica N.V. In addition, PR has served on a scientific advisory board for Gilead Sciences and serves on a data safety monitoring committee for Janssen Pharmaceutica N.V., for which his institution has received remuneration. KE has received honoraria from Abbott for educational lectures. JS has received research grants from the UK Medical Research Council. JS has received payment from Gilead Sciences, Inc for educational presentations.

Citation

Boulle A, Schomaker M, May MT, Hogg RS, Shepherd BE, et al. (2014) Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies. PLoS Med 11(9): e1001718.doi:10.1371/journal.pmed.1001718

Contact

Andrew Boulle
School of Public Health and Family Medicine
University of Cape Town
South Africa
+27 21 4066715
andrew.boulle@uct.ac.za

Jonathan Sterne
School of Social and Community Medicine
University of Bristol
United Kingdom
+44 117 928 7382
Jonathan.Sterne@bristol.ac.uk

Perspective Article

CMW's contributions to this work were supported by a UICC Fellowship funded by the Center for Global Health at the US National Cancer Institute. The funders had no role in the decision to publish or in the preparation of the manuscript.

Competing Interests

AB is a member of the Editorial Board of PLOS Medicine and served as Academic Editor for the linked article by Boulle and colleagues. All other co-authors declare that no competing interests exist.

Citation

Binagwaho A, Nutt CT, Mugwaneza P, Wagner CM, Nsanzimana S (2014) Convergence of Mortality Rates among Patients on Antiretroviral Therapy in South Africa and North America. PLoS Med 11(9): e1001719.doi:10.1371/journal.pmed.1001719

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