An ultra-short AZT regimen is just as effective as the longer AZT regimen used in resource-poor countries to prevent mother to child transmission, according to a Zimbabwean study presented today at the Fourteenth World AIDS Conference in Barcelona.
By implication, the ultra-short course regimen may also be as effective as the single dose nevirapine regimen being implemented or advocated in many resource-poor countries, since the nevirapine regimen was originally tested against the same multiple dose AZT regimen used as the control arm in this study.
The investigators found that the AZT short-course regimen was just as effective as the AZT short course regimen previously validated by a placebo controlled study in Thailand. The Thai regimen used AZT twice daily from week 36 of pregnancy until birth, with AZT dosed three hourly during labour, and no AZT for the infant.
The ultra short course regimen consisted of 300mg of zidovudine (AZT) every three hours during labour for the mother, while the infant received an AZT capsule dissolved in 30cc of water that had been boiled to sterilise it, divided into two hourly doses over the first three days of life.
The study randomised 222 women and infant pairs to receive either the Thai regimen or AZT during delivery, and both investigators and patients were blinded to which regimen they were receiving.
Data were available on the HIV status of 179 infants six weeks after birth The study found an 18.9% transmission rate in the Thai regimen arm versus a 15.7% transmission rate in the ultra short course AZT arm. Infant HIV status was established using viral load testing (Nuclisens, Organon Teknika) on dried blood spots.
At six weeks, 4.1% of infants were lost to follow-up, and at six months the lost to follow-up rate was 6.2%, a rate which compares favourably with other studies of interventions to prevent mother to child transmission carried out in Africa.
Michael Silverman of Health Canada, one of the study investigators, told aidsmap that the study results suggested that it was possible to reduce the price price of treatment to prevent mother to child transmission still further.
“This regimen costs $4 per mother paying full price for AZT, without any price reductions, compared to $6 for nevirapine.”
However, resource-limited countries are currently offered nevirapine free by Boehringer-Ingelheim, so cost may not be the major attraction of this approach to preventing mother to child transmission if such programmes become more widespread. However, where nevirapine is not available free, AZT could be used in the way studied in Zimbabwe, and could be affordable for many families (especially if generic AZT is available).
The effect on the mother’s future treatment options is also likely to make this approach attractive, at least in the short to medium term until triple therapy is available during pregnancy for mothers.
“The regimen reduces the risk of compromising the mother’s future treatment options because the mother is exposed to AZT for such a short period, so there is less risk of resistance”, said Michael Silverman.
“In the Petra study, mothers who developed resistance did so after a week or more of AZT treatment, and in the 012 study women were effectively receiving a week of nevirapine monotherapy from one dose of the drug due to the long half-life of the drug.”
The regimen is also easier to administer, said Michael Silverman, because it can be given when mothers attend the local hospital, does not require intravenous treatment of the child and does not require the use of a paediatric formulation that would be more expensive and require refrigeration. It is also more discreet when administered at home.
The study was conducted at the Salvation Army Howard Hospital in a rural area 80km north of Harare, the capital of Zimbabwe.
Thistle P et al. Superiority of an ultra-short zidovudine regimen in the prevention of perinatal HIV transmission in rural Zimbabwe. Fourteenth International AIDS Conference, Barcelona, abstract MoD3680, 2002.