PREGART

The challenge

Pregnant women are particularly badly affected by HIV infections. Pregnant women living with HIV have an eightfold higher risk of adverse pregnancy-related outcomes compared with women without HIV infections. In areas where HIV is common, HIV accounts for 12% of maternal deaths during pregnancy and soon after birth.

Because of concerns about the effects of drugs on the developing fetus, pregnant women are typically excluded from pivotal trials of new pharmaceutical interventions. This can delay the use of effective new treatments in such women. In addition, although pregnancy has a profound physiological impact on women, when drugs are recommended for use in pregnant women, it is usually based primarily on data from men and non-pregnant women.

For HIV treatment, WHO recommends dolutegravir-based regimens or low-dose efavirenz-based regimens. However, there are limited data from pregnant women on the efficacy and safety of low-dose efavirenz, or possible impacts on the health and development of  their babies.

The project

Funded through the EDCTP2 programme, the PREGART project has been carrying out a clinical trial comparing treatment outcomes for pregnant women living with HIV given either dolutegravir-based regimens or low-dose efavirenz-based regimens. The trial was due to recruit more than 1000 women at sites in Ethiopia and Uganda. 

However, the trial was badly disrupted by the COVID-19 pandemic, by insecurity in areas of Ethiopia where recruitment was taking place, and by an Ebola outbreak in Uganda. Funding from the Global Health EDCTP3 programme will enable the project to complete recruitment and follow-up of participants during pregnancy and for 12 months after birth to assess potential impacts on maternal health and infant development.

The project is comparing key aspects of HIV control, including maternal viral load at delivery, cases of maternal-to-child transmission of HIV, and adverse pregnancy outcomes. The 12-month follow-up will reveal whether either treatment has any significant impact on infant health and development. 

The project team is also monitoring bloodstream levels of the drugs to determine whether doses achieve therapeutic levels and to explore associations between drug levels and efficacy and safety signals. 

Impact

The PREGART study is providing key evidence on safe and effective HIV treatment for pregnant women. It will:

• Generate high-quality and directly comparable evidence of efficacy and safety for two possible antiretroviral treatments for pregnant women living with HIV in sub-Saharan Africa.
• Provide safety data on both pregnancy outcomes and early infant development. 

By ensuring the trial will be completed as originally planned, the new funding will enable the PREGART study to provide both global and national policymakers with critical information to inform the choice of antiretroviral treatment for pregnant women living with HIV in sub-Saharan Africa.