HIV Infection in Infants and Children: Tranmission

TRANSMISSION
Almost all HIV-infected children acquire the virus from their mothers before or during birth or through breastfeeding. In the United States, approximately 25 percent of pregnant HIV-infected women not receiving AZT therapy have passed on the virus to their babies. The rate is significantly higher in developing countries.

Prior to 1985 when screening of the nation's blood supply for HIV began, some children as well as adults were infected through transfusions with blood or blood products contaminated with HIV. A small number of children also have been infected through sexual or physical abuse by HIV-infected adults.

PREGNANCY AND BIRTH
Most MTCT, estimated to cause more than 90 percent of infections worldwide in infants and children, probably occurs late in pregnancy or during birth. Although the precise mechanisms are unknown, scientists think HIV may be transmitted when maternal blood enters the fetal circulation or by mucosal exposure to virus during labor and delivery. The role of the placenta in maternal-fetal transmission is unclear and the focus of ongoing research.

The risk of MTCT is significantly increased if the mother has advanced HIV disease, increased levels of HIV in her bloodstream, or fewer numbers of the immune system cells-CD4+ T cells-that are the main targets of HIV.

Other factors that may increase the risk are maternal drug use, severe inflammation of fetal membranes, or a prolonged period between membrane rupture and delivery. A study sponsored by NIAID and others found that HIV-infected women who gave birth more than 4 hours after the rupture of the fetal membranes were nearly twice as likely to transmit HIV to their infants, as compared to women who delivered within 4 hours of membrane rupture.

BREASTFEEDING
HIV also may be transmitted from a nursing mother to her infant. Studies have suggested that breastfeeding introduces an additional risk of HIV transmission of approximately 10 to 14 percent among women with chronic HIV infection. In developing countries, an estimated one-third to one-half of all HIV infections are transmitted through breastfeeding.

WHO recommends that all HIV-infected women be advised about both the risks and benefits of breastfeeding for their infants so they can make informed decisions. In countries where safe alternatives to breastfeeding are readily available and economically feasible, this alternative should be encouraged. In general, in developing countries where safe alternatives to breastfeeding are not readily available, the benefits of breastfeeding in terms of decreased illness and death due to other infectious diseases greatly outweigh the potential risk of HIV transmission.

PREVENTING MOTHER-TO-CHILD TRANSMISSION
In 1994, a landmark study conducted by the PACTG demonstrated that AZT, given to HIV-infected women who had very little or no prior antiretroviral therapy and CD4+ T-cell counts above 200/mm3, reduced the risk of MTCT by two-thirds, from 25 percent to 8 percent. In the study, AZT therapy was initiated in the second or third trimester and continued during labor, and infants were treated for 6 weeks following birth. AZT produced no serious side effects in mothers or infants. Long-term follow up of the infants and mothers is ongoing.

A few years later, another PACTG study found that the risk of transmitting HIV from an HIV-positive mother to her newborn infant could be reduced to 1.5 percent in those women who received antiretroviral treatment and appropriate medical and obstetrical care during pregnancy.

Combination therapies have been shown to be beneficial in treating HIV-infected adults, and current guidelines have been designed accordingly. In HIV-infected pregnant women, the safety and pharmacology of these potent drug combinations need to be better understood, and NIAID is conducting studies in this area.

The AZT regimen is not available in much of the world because of its high cost and logistical requirements. The cost of a short-course AZT regimen is substantially lower, but is still prohibitive in many countries. International agencies are studying whether there may be innovative ways to provide AZT at lower cost, for example, through reductions in drug prices to developing countries or partnerships with industry. As a result, NIAID continues to evaluate other strategies that may be simpler and less costly to prevent MTCT in various settings. In September 1999, one such study demonstrated that short-course therapy with nevirapine lowered the risk of HIV-1 transmission during the first 14 to16 weeks of life by nearly 50 percent compared to AZT in a breastfeeding population. As a follow up, NIAID released a final report on additional data showing that the results of nevirapine were sustained after 18 months. These findings have significant implications because this simple, inexpensive regimen offers a potential cost-effective alternative for decreasing MTCT in developing countries.

In addition, in April 1999 the International Perinatal HIV Group reported that elective caesarian section delivery can help reduce vertical transmission of HIV, though it is not without risk to certain women. When AZT treatment is combined with elective caesarian delivery, a transmission rate of 2 percent has been reported.

Because a significant amount of MTCT occurs around the time of birth, and the risk of maternal-fetal transmission depends, in part, on the amount of HIV in the mother's blood, it may be possible to reduce transmission using drug therapy only around the time of birth. NIAID has planned other studies that will assess the effectiveness of this approach as well as the role of new antiretrovirals, microbicides and other innovative strategies in reducing the risk of MTCT of HIV.