Clinical Development optimization

Adaptive trial design with historical control to optimize prevention of mother-to-child HIV transmission

A Bayesiann adaptive trial with a historical control was designed to accelerate and de-risk trial and to optimize prevention of mother-to-child HIV transmission.

Especially in low to middle income countries, pregnant HIV-infected women are not properly treated by anti-retroviral therapies, or not even diagnosed. This increases dramatically the risk of intrapartum and perinatal transmission. However recruiting women at high-risk remains a challenge.


Design a parsimonious adaptive single arm study to eradicate HIV transmission in high risk infected pregnant women

To recruit enough HIV-positive pregnant women to conduct a study.

Adaptive design with historical control arm to accelerate trial.

To demonstrate that adequate prevention is effective.

Methods & solution

A Bayesian adaptative trial design with a model-based meta-analysis

The study consisted in a Bayesian meta-analysis and transmission modeling based on historical standard of care data from the same population.

A trial simulator to calculate the probability of success and transmission rates.

An adaptive trial design with the possibility of early trial interruption in case of success.


A successful trial with sample size and trial duration divided by 5 vs. an alternative with standard randomized trial

This method resulted in a 5-fold reduction in total sample size and trial duration compared with a standard randomized trial.

No HIV transmission was observed among the 88 mother-infant pairs receiving antiretroviral intensification.

The success of the trial and registration led the WHO to change its guidelines for preventing HIV transmission.


An effective transmission prevention

  • Prevention of intrapartum HIV transmission in HIV-positive pregnant women receiving antiretroviral therapy has proven to be effective.
  • Based on this demonstration, WHO updated HIV prevention guidelines which led close to eradication of HIV transmissions in SouthEast Asia.WHO is also launching a similar platform trial in Africa.

Reference: Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery –