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

Billions of dollars are invested annually in pharmaceutical research and development to identify medications that are as effective as existing drugs but with fewer side effects. Currently, there are over 30 antiretroviral drugs in development to help treat and prevent human immunodeficiency virus (HIV) infection. Most of these drugs seek to improve clinical outcomes by reducing toxicity and thereby improving patient adherence and retention. However, the clinical benefits of less toxic regimens (e.g., improved adherence and retention) are rarely measured in real-world non-trial settings. 

In a new journal article published in the American Journal of Epidemiology, Jacob Bor and coauthors aim to fill this gap in the medical literature by presenting results from a study assessing the impact of a less toxic HIV treatment in Zambia and South Africa. Both countries adjusted their HIV treatment guidelines in 2007 and 2010, respectively, to recommend the drug tenofovir for first-line antiretroviral treatment (ART). The researchers compare patients presenting just before and after the guideline changes and estimate retention in care and other treatment outcomes at 24 months.

Main findings:

• The proportion of HIV patients initiating tenofovir increased strongly with the guideline changes in both countries: from 7.7 percent of patients to 89 percent in South Africa and from seven percent to 49 percent in Zambia.
• The change in guidelines resulted in a decrease in the proportion of patients switching to other antiretroviral drugs during the first 24 months on ART, from 19 percent to four percent in South Africa and seven percent to 4.7 percent in Zambia.
• In South Africa, the guideline change decreased patient attrition by 4.3 percent and in Zambia patient attrition decreased by 15 percent.
• The guideline change had no statistically significant impact on the number of deaths or patients’ immunological responses in either country.

The findings demonstrate that the guideline change of establishing tenofovir as the standard of care for first-line ART had mixed results in the countries studied. On the one hand, it improved retention in care in Zambia, providing strong evidence that side effects lead patients to stop therapy and that use of drugs without these side effects reduces attrition. On the other hand, South Africa’s experience—a very large shift toward tenofovir with little impact on patient attrition—points to the complications of scaling up these innovations and the importance of context in generalizing findings to other settings. 

Taken as a whole, the results indicate that innovations designed to reduce side effects may improve clinical effectiveness in addition to patient quality of life in some populations. Understanding these benefits and how they vary is critical to maximizing the population impact of investments in these new drugs.