Postnatal transmission of HIV to breastfed infants following short course ZDV regimen

Postnatal transmission of HIV-1 is of great concern among populations where breastfeeding is common practice. It is also speculated that risk of postnatal transmission could be greater following a maternal intervention due to rebound in maternal viral load after antiretroviral discontinuation.

ANRS 049a DITRAME (Abidjan, Côte d’Ivoire and Bobo-Dioulasso, Burkina-Faso) and RETROCI (Abidjan) in order to assess the postnatal transmission risk in a breastfeeding population after a maternal short course zidovudine (ZDV, AZT) regimen.

HIV-positive pregnant women were randomised at 36-38 weeks’ gestation between September 1995 and February 1998, to receive 250 mg or 300 mg oral zidovudine or placebo: one tablet twice daily until the start of labour. DITRAME participants then received a single oral zidovudine dose of 500 or 600mg, and RETROCI participants 300mg every three hours until delivery. DITRAME participants only then received a seven-day post partum maternal treatment of 500 or 600mg per day. There was no infant drug component in this study.

Postnatal transmission was defined as a child with a negative HIV-1 PCR at age 30 days who later became infected as defined by a positive HIV-1 PCR, or if aged 15 months, a positive HIV serology.

Of the 479 infants eligible for analysis, at 24 weeks 23/254 in the zidovudine arm (9.8%) and 19/225 (9.1%) in the placebo arm had become infected by postnatal transmission. The investigators reported the culmulative risks of postnatal transmission to be similar in both arms, at ages six, 12 and 24 months the risks were 3.4%, 9.2% and 9.8% vs 3.4%, 6.8% and 9.1% in the zidovudine and placebo groups respectively.

They reported the culmulative risk to be much higher among mothers with lower CD4 counts, ie less than 500 cells/mm3 than among those with higher than 500 cells/mm3 CD4. Among the women with lower CD4 cell count, they found 24 month postnatal transmission risks of 21.8% and 16.1% in the zidovudine and placebo arms respectively. This represented 86% and 68% of the cases in the respective arms.

Multivariate analysis evaluating intervention, maternal CD4 cell count and maternal viral load, revealed that at 24 months the zidovudine effect was not significant (hazard ratio zidovudine to placebo, 1.15; CI, 0.57-2.31). Maternal CD4 cell count of less than 500 cells/mm3 at study entry however, tripled the hazard for postnatal transmission compared to women with greater than 500 CD4 cells/mm3 (HR, 3.14; CI, 1.31-7.49). Women with higher plasma viral load at study entry also increased the hazard (HR, 2.65 for 1 log increase; CI, 1.75-4.00).

This study is the first to report that postnatal transmission risk is associated with maternal CD4 and viral load. The investigators raise the important issue that because postnatal transmission risk is substantially higher in women with a low CD4 count and that these women also have a higher risk of opportunistic infection and death “…maternal HAART would be specially beneficial for these women, both for themselves and also to reduce postnatal transmission”.

They conclude “…comprehensive and tailored approaches are especially needed for women with advanced HIV disease in order to fulfill the recently agreed United Nations target of reducing MTCT by 20% by the year 2005”.

Leroy V; John M. Karon JM; Alioum, A et al for the West Africa PMTCT Study Group. Postnatal transmission of HIV-1 after a maternal short-course zidovudine peripartum regimen in West Africa. AIDS 2003,17: 1493 – 1501.