BETHESDA, Md. A pregnant woman can transmit HIV to her infant even if she has little or no detectable HIV in her blood and a relatively intact immune system, according to a new report by researchers supported by the National Institutes of Health (NIH).
However, zidovudine (Retrovir, Glaxo Wellcome) reduced the risk of perinatal transmission, regardless of a womans viral load or CD4 T cell count. Therefore, researchers urged caregivers to offer zidovudine (ZDV) to all pregnant HIV-infected women, regardless of their stage of disease.
"HIV transmission to the infant is most likely to occur when a woman has large quantities of virus in her bloodstream, but there appears to be no absolute threshold of maternal viral load below which HIV is not transmitted from mother to infant, nor a safe maternal CD4 T cell level above which transmission never occurs," said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID).
Rhoda S. Sperling, MD, associate professor of obstetrics, gynecology and reproductive science at Mount Sinai School of Medicine in New York, and her colleagues found that the reduction in perinatal transmission after ZDV could only partially be explained by the drugs effect of reducing HIV in a mothers bloodstream.
"The benefits of ZDV in reducing perinatal transmission appear to be due in part to mechanisms other than decreasing the amount of HIV in a womans plasma," said Sperling. "Even when antiretroviral drugs with a greater impact on reducing viral load are indicated for the health of a pregnant HIV-infected woman, she and her physician should strongly consider incorporating ZDV into her treatment regimen and should continue ZDV during delivery and to the newborn, according to the ACTG 076 protocol," she said in a press release from NIH.
"Further research is needed into the mechanisms whereby ZDV reduces perinatal HIV transmission, as well as into the risk factors for transmission at all levels of maternal viral load," she added. The study was published in the New England Journal of Medicine.
A related editorial by Catherine M. Wilfert, MD, of Duke University Medical Center appears in the same issue. Sperling and Wilfert are investigators within the Pediatric AIDS Clinical Trials Group, a network of clinical trials sites sponsored by NIAID and the National Institute of Child Health and Human Development (NICHD).
The article is the second publication from a randomized, double-blind clinical trial known as ACTG 076. The study enrolled 477 pregnant women with HIV between April 1991 and December 1993, and assessed the safety and efficacy of ZDV in reducing maternal-infant transmission. Women enrolled in the study had CD4 T cell counts greater than 200 cells/mm≥ at study entry. They received ZDV beginning in the second or third trimester and during labor and delivery; their newborns received the drug for the first six weeks of life.
The first publication from ACTG 076 analyzed data from 363 mother-infant pairs in which at least one culture of the infants blood had been performed and demonstrated that the ZDV regimen reduced mother-to-infant transmission by approximately two-thirds, with minimal short-term toxic effects (The New England Journal of Medicine, 11/03/94).
The current analysis of ACTG 076 data included 402 mother-infant pairs in which the HIV status of the infant was definitively known at 18 months of age. Among the mother-infant pairs, 198 received ZDV during the study and 204 received placebo. Fifteen infants in the ZDV group (7.6%) had HIV; 46 infants (22.6%) in the placebo group had HIV.
The investigators tested stored samples of maternal blood collected when women entered the study and when they delivered their infants. For their analyses, the researchers used the branched DNA assay and a reverse transcription PCR assay, which were not available at the start of ACTG 076. These assays measure the viral load or the amount of HIV RNA in a persons bloodstream.
In both the ZDV and placebo groups, perinatal transmission occurred within a wide range of viral loads, including instances when women had undetectable levels of HIV as well as when women had viral loads greater than 100,000 RNA copies/mL of blood.
In the placebo group, a high maternal viral load at study or at delivery, or a positive blood culture, was associated with an increased risk of transmission. Among the women with the highest viral loads, the rate of transmission was more than 40%. Transmission was also more likely when a woman not receiving ZDV had a low CD4 cell count. However, even among 119 untreated mothers with CD4 T cell counts above 500/mm≥, the transmission rate was 21%.
ZDV reduced median maternal HIV RNA levels 1.7-fold between study entry and delivery. This modest change, however, could not account for the substantially reduced transmission rate in the ZDV group, a benefit that was observed regardless of maternal viral load and CD4 counts.
New data indicate that perinatal prevention efforts also have dramatically reduced AIDS cases in children. On Nov. 21, 1996, the CDC released information that documents a substantial reduction in perinatally acquired AIDS cases. These new data confirm what earlier research had indicated that routine and universal counseling and voluntary testing, combined with ZDV therapy is highly effective in preventing the perinatal transmission of HIV.
By late 1995, more than 1.5 million children worldwide had been infected with HIV. More than 90% of children with HIV infections contracted the virus from their HIV-infected mothers. In the United States, 7,472 cases of AIDS among children younger than 13 years had been reported to the CDC as of Sept. 30, 1996. HIV infection ranks seventh among leading causes of death for children ages 1 to 14 years. In many cities in the eastern United States, HIV disease is the leading cause of death among children ages 2 to 5.
For more information:
- Sperling RS, Shapiro DE, Coombs RW, et. al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med. 1995;335:1621-29.
- Wilfert CM. Beginning to make progress against HIV. N Engl J Med. 1996;335:1678-80.
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