Comparative Safety of Antiretroviral Drugs to Treat HIV During Pregnancy

Abstract

Each year, nearly 1.5 million women with HIV become pregnant, and require antiretroviral treatment to reduce risk of perinatal transmission of the virus and improve their own health. The safety of currently approved antiretroviral medications for the fetus is largely unknown; recommendations about preferred regimens during pregnancy are often based on a small body of clinical safety data, expert opinion, and programmatic considerations, including regimen harmonization across sub-populations.

Therefore, there is a public health need to identify the specific antiretroviral drugs and combinations of drugs that are safest for use during pregnancy. Across the papers that comprise this Dissertation, we apply different epidemiological methods to observational data sources in order to provide information on clinically-motivated questions.

In Chapter II, we used descriptive statistics to explore how substance use, one important risk factor for adverse infant birth outcomes, changed over time among pregnant women with HIV in the US. We found that substance use in this population dramatically decreased from 1990 to 2012, and that substance use had correlations with treatment, which means it may act as an important confounder in subsequent antiretroviral safety studies.

In Chapter III, we further investigated the relationship between specific antiretroviral regimens and adverse birth outcomes, providing information on safety questions raised by a recent clinical trial. Pooling data from two prospective cohorts, we compared three antiretroviral regimens and concluded that the use of tenofovir with protease inhibitors not including lopinavir/ritonavir do not increase adverse birth outcomes.

In Chapter IV, we examined the relationship between first trimester use of the antiretroviral zidovudine and congenital malformations. We summarized results of published studies using a systematic review and meta-analysis, and used Bayesian methods to incorporate this information with new data from Medicaid. We concluded that there appears to be a link between first trimester zidovudine use and increased risk of male genital malformations.

We hope that the research undertaken in this Dissertation will substantially contribute to the growing body of antiretroviral safety information available to women with HIV and their clinicians, ultimately allowing them to make more well-informed treatment decisions.