Send to

Choose Destination
Am J Epidemiol. 2018 Sep 1;187(9):1990-2001. doi: 10.1093/aje/kwy093.

Medication Side Effects and Retention in HIV Treatment: A Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia.

Author information

Department of Global Health, School of Public Health, Boston University, Boston, Massachusetts.
Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts.
Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Division of Infectious Diseases, Department of Medicine, Tygerberg Academic Hospital, University of Stellenbosch, Cape Town, South Africa.
Kheth'Impilo AIDS Free Living, Cape Town, South Africa.
The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Africa Health Research Institute, Durban, South Africa.
School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.
Research Department of Infection and Population Health, University College London, London, United Kingdom.
Institute of Public Health, School of Medicine, Heidelberg University, Heidelberg, Germany.
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa.
Division of Public Health Medicine, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
Center for Infectious Disease Research in Zambia, Lusaka, Zambia.


Tenofovir is less toxic than other nucleoside reverse-transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of human immunodeficiency virus (HIV)-infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir for first-line ART. We applied regression discontinuity in a prospective cohort study of 52,294 HIV-infected adults initiating first-line ART within 12 months (±12 months) of each guideline change. We compared outcomes in patients presenting just before and after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24 months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentages of patients initiating tenofovir in South Africa (risk difference (RD) = 81 percentage points, 95% confidence interval (CI): 73, 89) and Zambia (RD = 42 percentage points, 95% CI: 38, 45). With the guideline change, the percentage of single-drug substitutions decreased substantially in South Africa (RD = -15 percentage points, 95% CI: -18, -12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD = -1.8% (95% CI: -3.5, -0.1); complier relative risk = 0.74) but not in South Africa (RD = -0.9% (95% CI: -5.9, 4.1); complier relative risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts.

[Available on 2019-09-01]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center