HIV-infected women with large quantities of HIV RNA in their bloodstream are more likely to transmit the virus to their babies than women with a lower viral load, according to several recent studies.
However, most of these studies have not demonstrated a well-defined threshold of maternal viral load above which HIV transmission is highly likely or below which it is unlikely.
Therefore, many experts believe that HIV-infected pregnant women, regardless of their virus levels, should strongly consider taking AZT to prevent transmission of HIV to their newborns. A previously reported NIAID-sponsored study (ACTG 076) demonstrated that a specific regimen of AZT treatment given to an HIV-infected woman during pregnancy and to her baby after birth can reduce maternal transmission of HIV by two-thirds (see The New England Journal of Medicine, Nov. 2, 1994).
Researchers have subsequently shown that this AZT regimen has reduced perinatal transmission in populations in which it has been used.
New Data Presented at Retroviruses Conference
At the 3rd Conference on Retroviruses and Opportunistic Infections in Washington, D.C., Sandra K. Burchett, M.D., of Children's Hospital in Boston presented data from the NIAID-supported Women and Infants Transmission Study (WITS) (abstract LB3). Dr. Burchett and her colleagues analyzed plasma samples from 115 HIV-infected women throughout pregnancy and found that very low viral loads were generally associated with lack of transmission, but that transmission occurred in women with all ranges of viral load.
In a separate report (abstract LB1), Rhoda S. Sperling, M.D., of Mount Sinai Medical Center in New York City, co-chair of ACTG 076, presented new information from a follow-up analysis of that study. In findings akin to those from the WITS study, Dr. Sperling reported that in the absence of any treatment, the risk of HIV transmission from mother to infant is higher for women with high levels of HIV RNA, but that transmission occurred even at low levels of RNA. The investigators found that AZT reduces the risk of transmission for women with both high and low levels of HIV, but that not all of the effects of AZT on HIV transmission can be attributed to a decrease in viral load.
In a related talk (abstract 30), Nathan Shaffer, M.D., of the Centers for Disease Control and Prevention reported finding an association between high maternal viral load and an increased risk of perinatal transmission in analyses of 146 HIV-infected pregnant women in Thailand. Among these women, who had access to good medical care, did not breast-feed, and did not receive AZT, the investigators observed an increasing risk of transmission with higher levels of maternal RNA, but no minimum threshold below which transmission did not occur. Dr. Shaffer and colleagues also found that HIV-infected children born to women with high viral loads had a much higher risk of early death than HIV-infected children born to women with low viral loads.
A fourth presentation (abstract LB2) by Richard A. Koup, M.D., of Aaron Diamond AIDS Research Center in New York City included data from an Ariel Project study of 151 HIV-infected pregnant women. Dr. Koup and his colleagues found an increasing risk of transmission with high virus load but also found no minimum maternal viral threshold for transmission of HIV from mother to child.
A recent publication (JAMA, Feb. 28, 1996) by Yvonne Bryson, M.D., and Ruth Dickover, Ph.D., of UCLA Medical Center and their colleagues suggests that specific low levels of virus at delivery are associated with a low risk of transmission, and therefore represent a goal for assessing potential therapies for reducing perinatal transmission. Conversely, the authors defined a high viral load above which transmission was more likely, particularly in women who transmitted the virus to their infants prior to birth.
However, the authors were cautious in defining the clinical utility of measurements of viral load at this time and advise against using any specific copy number as a threshold for altering clinical care. In the future, monitoring levels of virus during pregnancy may identify women who may benefit from additional treatment if they have high or rising virus loads despite AZT therapy.
"Further definition of the risk factors associated with transmission at both high and low viral loads, such as the timing of transmission or occurrence of obstetrical complications (especially at delivery) will be important for improved strategies for interruption of transmission," says Dr. Bryson.
--Laurie K. Doepel