Well thought out procedures to ensure adherence to nevirapine treatment around the time of birth may lead to substantial improvements in the protection that nevirapine can provide from mother to child HIV transmission, according to a US/South African team working at St Mary's Hospital, run by the Catholic Church in the heart of KwaZulu Natal. A presentation by Krista Dong at last week's South African AIDS Conference in Durban examined what factors had caused the clinic to record a transmission rate of around 3%, compared with the 10-15% transmission rate normally seen when nevirapine is used to prevent mother to child transmission.
A clinical study aimed to enrol sufficient mothers into the programme so that 60 babies with HIV could be randomised to receive different patterns of early ARV treatment. ARV treatment would also be provided to their mothers, if needed. In a district where 30% of pregnant women were HIV-positive, it was not expected to take long.
However, the team found that after 54 full-term births, just one child was HIV-positive. There was at least one more HIV positive baby among the pre-term and underweight babies, whose mothers' viral load tended to be higher and CD4 counts lower (another two were not tested). The pre-term baby was PCR positive on day 1, presumably due to intrauterine transmission. Two HIV positive babies out of 60 or one out of 54 give transmission rates of 2 to 3%.
The researchers believe that the detailed planning and training that takes place with mothers to ensure adherence and tackle stigma probably explains why transmission rates are so low.
Expectant mothers who joined the programme received four three-hour training sessions at weekly intervals. The four modules were as follows:
- Module 1 - discussion of stigma and disclosure, positive living including nutritional support.
- Module 2 - HIV/AIDS, CD4/VL testing, OIs, OI prophylaxis (women received their own VL and CD4 results from blood samples taken the week before).
- Module 3 - MTCT, NVP infant feeding, labour and delivery ward tour. To make sure they would have access to the NVP dose, they played games about where the NVP was kept; the ward tour was to demystify and familiarise women with the whole place. Infant feeding was about exclusive breast feeding, which was the only option recommended by the hospital.
- Module 4 - details of the proposed study, adherence to ARVs, making a treatment plan (when and how she would deliver), treatment options for mums.
When the woman goes into labour, she is trained to record the time she takes her NVP and give this to the staff on admission to hospital. (If the birth happens rapidly, i.e less than 1-2 hours after maternal dosing, the baby will be treated straight away rather than after 72 hours, since insufficient time will have elapsed for a therapeutic dose to have crossed the placenta.) Admission lasts 4-6 hours after a vaginal delivery, longer for a caesarean. When it is known that women are positive, obstetric procedures such as the use of scalp electrodes on the baby are avoided, along with anything else that could increase blood-exposure.
Babies were tested using PCR at one day, 7 days and 28 days after birth, with results given to the mother three days later.
The superior performance of NVP in HIVNET 012 has been attributed by many to the fact that adherence to the NVP regimen was simpler than adherence to the short-course AZT alternative regimen. However, the trial has been criticised by the South African Medicines Control Council for failing to show that women actually took the antiretrovirals they were supposed to take. This report suggests that in HIVNET 012, even the adherence to the NVP arm of the trial may have been suboptimal and that HIVNET 012 may have underestimated the potential efficacy of the drug to prevent mother to child transmission.
This also suggests that simple adherence measures - including involvement of a male partner - can further improve the performance of MTCT prevention programmes even where these are limited to two-dose nevirapine regimens.
Dong K et al. Prevention of mother-to-child transmission of HIV-1 via intensive pre-natal training and closely monitored use of single dose Nevirapine. South African AIDS Conference, Durban, abstract T3-S8-A49, 2003.