A joint project of four universities, PHASES seeks ethical solutions to advance research at the intersection of women’s reproduction and HIV prevention, treatment, and management.

 

Project Description

Despite tremendous advances in the science to prevent, treat, and manage HIV since the emergence of the epidemic, we still know very little about how to best address the needs of a key population affected by HIV: pregnant women. An estimated 16.1 million women are living with HIV worldwide, with millions more at risk of becoming infected. Many of these women are of reproductive age, posing important medical questions about how best to prevent HIV in pregnant women and manage HIV and concurrent medical conditions during pregnancy. We know that pregnancy can substantially alter drug metabolism, with implications for appropriate dosage and toxicity profiles of existing therapies. Yet in spite of the critical need to assess optimal treatment and prevention options – for both the mother and developing child – there is surprisingly little evidence on how necessary therapies will work during pregnancy.

Ethical and legal concerns of including pregnant women in studies have led to widespread exclusion of this population from medical research. But without the systematic generation of evidence, these women and their health care providers must face difficult clinical decisions in the absence of adequate information on safety and efficacy of new antivirals, preventive agents, and drugs to treat co-infections and other associated diseases.

The categorical exclusion of pregnant women from research is unacceptable. A new paradigm must be forged to safely and responsibly include pregnant women in research so that all pregnant women and their developing children will ultimately benefit from interventions critical to their health and wellbeing.


Project Aims

This project aims to develop immediate, ethically acceptable strategies to conducting research on HIV treatment and prevention during pregnancy. PHASES will focus on three specific areas of HIV research in urgent need of an evidence base applicable to pregnant women:

PREVENTION

Pregnant women are up to two-times more likely to acquire HIV than other women, and infection during pregnancy has been demonstrated to increase the odds 15-fold of maternal- to-child transmission. Yet many prevention trials, including the groundbreaking CAPRISA 004 microbicide study, exclude pregnant women.

TREATMENT OF CO-INFECTION

Studies have reported that HIV-infected pregnant women have active Tuberculosis (TB) at about 10 times the rate of HIV-uninfected pregnant women, and in South African teaching hospitals TB accounted for 15% of maternal mortality. However, many current TB regimens are not recommended during the first trimester of pregnancy (or for women with childbearing potential), and the emergence of drug-resistant TB presents further challenges. While a new class of antituberculosis drugs is revolutionizing the treatment of drug-resistant TB, pregnant women have been excluded from trials and there are no data to guide dosing or treatment decisions, even though drug-resistant TB associated with HIV is a major cause of perinatal morbidity and mortality.

MANAGEMENT OF HIV

Studies of optimal dosing strategies for new antivirals in pregnant women have lagged behind the use of these new drugs in the clinical setting, meaning that pregnant women are being prescribed medication solely based on studies in non-pregnant individuals. This can lead to sub-optimal or insufficient dosing with unknown associated toxicity.


Project Objectives

  • Identify scientific priorities for research addressing pregnancy and HIV prevention, treatment, and management
  • Characterize the perceived barriers to including pregnant women and women who may become pregnant in HIV-related research
  • Explore potential novel study designs that will minimize ethical and legal concerns of HIV research with pregnant women and women who may become pregnant
  • Develop a conceptual ethical framework for HIV research in pregnancy that is responsive to the priority areas and current barriers

Areas and Populations of Research Interest

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Project Activities

In order to seek ethically and scientifically responsible solutions for enhancing society’s knowledge base to effectively prevent HIV and manage HIV treatment during pregnancy, we will engage leading HIV investigators, bioethicists, and legal and regulatory experts to develop an action- guiding ethical framework to navigate the complexities of including pregnant women in research.

To gather information on the most pressing research priorities, identify the major obstacles to conducting HIV research with pregnant women and women who may become pregnant, and strategize potential solutions within the currently regulatory framework, we will conduct a series of engagement meetings with:

  • Centers for AIDS Research (CFAR) investigators
  • Legal and regulatory experts
  • Experts in clinical research ethics and feminist bioethics

Following these engagement sessions, we will develop and vet:

  1. A robust conceptual framework for ethically permissible HIV research with pregnant women and women who may become pregnant
  2. A set of practical, workable, consensus recommendations responsive to the priorities and current barriers
  3. The framework and recommendations will provide useful guidance to investigators, ethics review committees, and policy makers, and enable investigators and the larger research enterprise to address critical questions related to HIV and the optimal care for women who are or may become pregnant.  In turn, health providers worldwide will be able to make evidence-informed clinical decisions to best promote the health of these patients.

 

The first phase of this project is made possible by a grant from the National Institute of Allergy and Infectious Diseases (NIAID).