Short course AZT prevented MTCT of HIV only for women with low viral load

In 1998, several years after a complicated AZT-based regimen to prevent mother to child transmission of HIV was proven in the United States, a simplified AZT regimen was demonstrated to be effective for use in resource-limited settings in Thailand. At that time, an ongoing placebo-controlled trial in Cote d’Ivoire, West Africa (RETRO-CI), of AZT administered during the final few days of pregnancy and then throughout labor and delivery was halted and all enrolled women given the drug. Per the protocol, women and their infants had follow-up visits at 1 and 3 months, then every three months until the child was two years old. Blood samples were collected from the infants at each visit and HIV status established by HIV-1 DNA PCR. The mother’s baseline viral load and CD4 count were determined at enrollment. No treatment was provided after birth to either mother or child, and participants breast-fed their children. The main efficacy results of this study were reported in 1999.

In the December 1 issue of the Journal of Acquired Immune Deficiency Syndromes, Denise Jamieson and colleagues from the U.S. Centers for Disease Control (CDC) and from Projet RETRO-CI in Abidjan, report on an analysis of the maternal risk factors associated with transmitting HIV to children in the study by the 1-month and the 24-month visit. In particular, this analysis looked at the efficacy of the treatment versus placebo as stratified by maternal viral load. Among 250 infants in this analysis (AZT = 126; placebo = 124), 42 had become HIV DNA positive within the first month with an additional 20 found positive at week 24. Overall, at month one, 15 infants of treated mothers (11.9%) and 27 infants of untreated mothers (21.9%) were HIV positive. By 24 months, infections in the AZT group had doubled to 22.1%, while those in the placebo group had increased to 29.2%

But when analysed by viral load, the benefit of treatment was not as clear. No mother with undetectable (

The main benefit of AZT in this population was seen in women with viral load between 10,000 and 50,000 copies/mL. Only 4 of 32 (12.5%) women who received AZT versus 13 of 41 (32%) of placebo recipients had infants who were infected within the first month. At 24 months the proportions infected were 21% and 41%, respectively. The treatment effect was also seen among women with CD4 counts above 350 cells/mm3 at month one. Other, non-treatment, factors associated with perinatal HIV transmission in this study were obstetric events that caused bleeding, young age, prior stillbirth and advanced HIV disease. The study is not able to report on risk factors for transmission that may have occurred after the first month.

The authors note that in other trials of AZT to prevent mother to child transmission of HIV, including the original PACTG 076 study in the U.S., the intervention was reported as efficacious across all viral load strata. The finding of benefit only in women with viral load below 50,000 copies/mL also contrasts with results from the HIVNET 012 study of nevirapine in a breast-fed population, which found the greatest effect in women with low CD4 counts and higher viral load. The authors anticipate that reports from ongoing trials in breast-feeding populations will provide additional, clarifying data.