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.
Objectives
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.
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A trial simulator to calculate the probability of success and transmission rates.
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An adaptive trial design with the possibility of early trial interruption in case of success.
Results
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.
Impact
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 – https://pubmed.ncbi.nlm.nih.gov/32205720/