WASHINGTON, D.C. CD4 counts and viral load may be factors in perinatal transmission of HIV, according to John Sullivan, who spoke here at the Fourth Annual Conference on Retroviruses and Opportunistic Infections.
More than 90% of children with HIV acquired the virus from their mothers. The transmission of the virus most often takes place in utero or during the intrapartum period, said Sullivan.
Sullivan's presentation focused on the understanding of vertical HIV transmission and the early virological and immunological pathogenic events. In particular, he discussed studies done as part of the Pediatric AIDS Clinical Trials Group (ACTG).
In 1990, Sullivan and several other investigators began taking samples of cord blood within the first two days of a baby's life. These samples demonstrated that there were infants who were born with cord blood, positive by culture or by P24 antigen, and that these samples could be used to isolate HIV. These samples also showed that some infants who appeared to be HIV negative in the first 48 hours of life subsequently became culture positive after the first few days following the birth.
It was through these studies that Sullivan and his colleagues came to the conclusion that HIV was being transmitted to infants in utero and during intrapartum. The model for this discovery was hepatitis B transmission. Thus, the working definition for in utero transmission was individuals who were culture positive within the first 48 hours of life, and, the working definition for intrapartum was individuals who were culture negative at birth and for the first few days, but became culture positive.
There are several ways that HIV is transmitted to infants in utero and during the intrapartum period. Infants in utero are exposed to the virus through maternal blood. However, transmission of the virus during the intrapartum period occurs when the infant is exposed to infected maternal vaginal secretions. Sullivan discussed the Eve Study, done by Emory University in Atlanta, which looked at RNA in vaginal secretions. The study found several hundred to hundreds of thousands of copies of RNA in vaginal secretions, he said, adding that this shows that vaginal secretions could be a source for viral infection during the intrapartum period.
Ruth Ruprecht and her colleagues illustrated that HIV can also be transmitted to infants through the mucosa. In that study, Ruprecht dropped HIV on the mucosa of infant monkeys or fed the virus to the monkeys orally, and they quickly became infected.
The mucosa is a likely port of entry in terms of intrapartum transmission, said Sullivan, vice chairman of research at the University of Massachusetts Medical School's department of pediatrics.
But what do maternal factors determine if the virus will be transmitted to the infant? There is evidence that suggests maternal CD4 counts and viral loads may be factors, he said.
ACTG 076 showed that women who received a placebo rather than an antiretroviral drug during the study and had CD4 T cell counts of 200 cells/mm≥ to 349 cells/mm≥ experienced a transmission rate of 40.6%. Those women in the placebo group who had CD4 counts greater than 500 cells/mm≥ had a transmission rate of 21%.
The Women & Infants Transmission Study demonstrated that women who have CD4 percentages less than 20% have an approximate one in three transmission rate, Sullivan said. Women who have 35% or more CD4 T cells have a transmission rate of less than 5%.
"Similarly, if one looks at viral load, there are a number of studies now that have demonstrated that while there is not a threshold, there is a strong relationship between the viral load and the transmission rate," Sullivan said. In the O76 protocol, women in the placebo group who had greater than 15,700 RNA copies/mL had transmission rates of 42%. Those women in the placebo group who had less than 1,700 copies/ mL had transmission rates of 7%.
In determining when transmission will take place, in utero or during the intrapartum period, Sullivan mentioned a study conducted in France by Christine Rouzioux and her colleagues which estimated that 65% of infants are infected in the intrapartum period. A number of U.S. studies resulted in similar numbers, with 60% to 70% of infants being infected intrapartum and 20% to 30% acquiring the virus in utero.
Another study conducted by investigators in Durban, South Africa, shows that the transmission pattern between mothers and infants is similar in the developing world, Sullivan said. Seventy-nine percent of the infants in the study were infected in the intrapartum period or through breastfeeding.
Sullivan also referred to a study done by David Katzenstein and colleagues in Zimbabwe, which suggested that 70% of the infants they studied were infected with HIV in utero. However, Sullivan questioned this study because there were a number of samples missing from it. He said if one added up all the potential samples that could have been looked at, then the study might have shown a transmission rate of 50% in utero and 50% intrapartum.
"I do think it's going to be of continued importance, especially as we begin to plan interventions in the developing world, to understand better the relationship between in utero and intrapartum transmission in different parts of the world," Sullivan said.
In stressing the importance of the link between mother and infant when transmitting HIV, Sullivan referred to a talk Peter Piot gave at the conference. In his talk, Piot said there were 8,500 new HIV infections occurring each day worldwide, which by 2000 will be an accumulated 30 million to 49 million new infections. Fifty percent of these new infections will be in women age 14 to 24 years. Of these, 6 million will be pregnant women, resulting in up to 10 million infected children, Sullivan said.
To decrease the number of infected children, physicians must recognize the two periods during which transmission can occur and intervene immediately with the available antiretroviral therapies. When these therapies are used, the factors leading to transmission, low maternal CD4 cell counts and high maternal viral loads, can reduce the chances of transmission.
For more information:
- Sullivan J. Perinatal transmission and early virus replication events in babies. Presented at the Fourth Annual Conference on Retroviruses and Opportunistic Infections. Jan. 22-26. Washington, D.C.
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