The PREGART study is evaluating two new first-line antiretroviral treatment regimens in pregnant women living with HIV.

Improving treatment of HIV in pregnant women

New treatment regimens are typically first tested in clinical trials that exclude groups such as pregnant women. Without further trials, pregnant women may therefore not benefit from advances in treatment.

In 2016, almost 750,000 women of reproductive age became HIV-positive, most of them in sub-Saharan Africa. Effective treatment is important not just for the health of mothers but also to prevent mother-to-child transmission of HIV.

The challenge

The PREGART trial is evaluating two possible enhancements to antiretroviral therapy in pregnant women. The first is use of dolutegravir, which has shown greater inhibition of viral replication than other first-line treatments and is less likely to be discontinued by patients. The second is a lowering of the dose of efavirenz, as standard-dose efavirenz may be associated with greater toxicity in pregnancy.

Lack of safety and efficacy data on the use of dolutegravir and low-dose efavirenz in pregnant and breastfeeding women has been identified as a priority evidence gap by WHO. Preliminary observational data from Botswana suggested that dolutegravir might be associated with an increased risk of neural tube defects if used during the first trimester of pregnancy. However, the numbers are small, and it is difficult to draw firm conclusions in advance of the final results. Nevertheless, WHO has updated its recommendation on the use of dolutegravir among pregnant women during the first trimester of pregnancy, and women in the first trimester of pregnancy will not be recruited into the trial.

The PREGART trial will compare triple therapy regimens containing dolutegravir and low-dose efavirenz with standard efavirenz-containing regimens, and with each other. It aims to enroll nearly 2,000 women in Ethiopia and Uganda.

The trial will also undertake pharmacokinetic and pharmacogenetic studies to see how genetic variation affecting the enzymes that metabolise dolutegravir and efavirenz influence the distribution of the drugs in the body. These studies will be important for determining the most appropriate dosing of dolutegravir in women in sub-Saharan Africa.

The project

The PREGART trial will provide key safety and efficacy data on two potentially superior antiretroviral drugs for pregnant and breastfeeding women, and on the appropriate dosing for women living in sub-Saharan Africa.

Impact


crucial in

widening African

children’s access

to antiretrovirals

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

New treatment regimens are typically first tested in clinical trials that exclude groups such as pregnant women. Without further trials, pregnant women may therefore not benefit from advances in treatment.

In 2016, almost 750,000 women of reproductive age became HIV-positive, most of them in sub-Saharan Africa. Effective treatment is important not just for the health of mothers but also to prevent mother-to-child transmission of HIV.

The PREGART trial is evaluating two possible enhancements to antiretroviral therapy in pregnant women. The first is use of dolutegravir, which has shown greater inhibition of viral replication than other first-line treatments and is less likely to be discontinued by patients. The second is a lowering of the dose of efavirenz, as standard-dose efavirenz may be associated with greater toxicity in pregnancy.

Lack of safety and efficacy data on the use of dolutegravir and low-dose efavirenz in pregnant and breastfeeding women has been identified as a priority evidence gap by WHO. Preliminary observational data from Botswana suggested that dolutegravir might be associated with an increased risk of neural tube defects if used during the first trimester of pregnancy. However, the numbers are small, and it is difficult to draw firm conclusions in advance of the final results. Nevertheless, WHO has updated its recommendation on the use of dolutegravir among pregnant women during the first trimester of pregnancy, and women in the first trimester of pregnancy will not be recruited into the trial.

The PREGART trial will compare triple therapy regimens containing dolutegravir and low-dose efavirenz with standard efavirenz-containing regimens, and with each other. It aims to enroll nearly 2,000 women in Ethiopia and Uganda.

The trial will also undertake pharmacokinetic and pharmacogenetic studies to see how genetic variation affecting the enzymes that metabolise dolutegravir and efavirenz influence the distribution of the drugs in the body. These studies will be important for determining the most appropriate dosing of dolutegravir in women in sub-Saharan Africa.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The PREGART trial will provide key safety and efficacy data on two potentially superior antiretroviral drugs for pregnant and breastfeeding women, and on the appropriate dosing for women living in sub-Saharan Africa.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

Projects: CAPRISA 018 study

Project lead: Professor Salim Abdool Karim, Centre for the AIDS Programme of Research in South Africa, South Africa

Countries involvedFrance, The Netherlands, South Africa

Target population(s): Women

Year funded: 2017

EDCTP funding: €9.8 M

Total project funding: €11.4M plus donation of study drugs

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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