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Update on Mother-to-Child Transmission

Fall 1998

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

In an ongoing effort to drive the rate of mother-to-child transmission of HIV (vertical transmission) to ever lower levels, numerous strategies are being explored. At the World AIDS Conference in Geneva this summer, several very encouraging reports on the effectiveness of Caesarean sections (C-sections) were presented. In addition, several small studies assessed the benefits and safety of combination therapy during pregnancy and had mixed outcomes. In the developing world, the transmission of HIV to infants through breast-feeding continues to be a major problem.

Elective C-sections

A three-part course of AZT treatment (administered before birth orally, during labor with an IV infusion, and to the newborn orally) has been proven to reduce the rate of vertical transmission by two thirds, from 25% to 8%. However, the role that the mode of delivery plays has been less clear. Since a large proportion of vertical transmission occurs at or near delivery, any intervention at this time might prove beneficial. Elective (non-emergency) C-section prior to the time the mother's water breaks can prevent the infant from being exposed to maternal blood and secretions. Up until now, studies attempting to demonstrate the effectiveness of such C-sections in reducing vertical transmission have been inconclusive. Presentations at Geneva revealed the most convincing data as yet on enhanced reduction in vertical transmission in women who were both on antiretroviral treatment and chose elective C-sections.

Several European studies provided important information. A large French group reported that among 902 women treated with AZT, elective C-section resulted in a rate of vertical transmission of only 0.8% compared to 6.6% for normal vaginal delivery. A Swiss group reported that there were no cases of vertical transmission among 45 women who completed the full three-part AZT treatment and had elective C-section. A German study of 80 women who had elective C-section performed in addition to AZT treatment found that the rate of transmission was 2.5% as opposed to 7% for vaginal deliveries. In Italy, a five-year international trial of pregnant HIV-positive women with similar antiretroviral regimens found that of the 133 children delivered by C-section, 3% contracted HIV compared to 10.3% of 132 infants delivered vaginally.

The largest survey by far was conducted by the NIH-funded International Perinatal Group, which performed an analysis of data from five European and ten North American prospective studies on a total of 8,533 mother-child pairs. After adjusting for receipt of antiretroviral therapy, maternal disease progression and birth weight, risk of vertical transmission was reduced by over 50% with elective C-section compared to other modes of delivery. In women who received antiretroviral therapy, the rate of transmission was 2% with elective C-section and 7.3% with other modes of delivery.

The enhanced protection of an elective C-section must be weighed against the risk of postoperative complications and each woman's situation should be considered individually. Obviously, not all women will have access to or be able to afford a C-section, especially in the developing world.

Combination Therapy

Beyond AZT, there is not much information from clinical trials to help an HIV-positive pregnant woman make treatment decisions. While using combination therapy may be best for her own health, she will also be concerned about the safety of her infant. Ongoing studies are assessing the effect of combination therapy on pregnancy outcomes.

San Francisco General Hospital reported that choice of treatment among pregnant HIV-positive women has shifted from monotherapy to dual to triple combination therapy over the past three years. Among women in the clinic, combination therapy has been well tolerated. No maternal or fetal complications have been observed. Of the 60 infants born since 1995, 43 are uninfected and 17 are less than six months old but have so far tested negative.

The Los Angeles County-University of Southern California Medical Center presented the results of a case review of 14 HIV-positive pregnant women who received triple combination therapy including nevirapine, AZT and another nucleoside analog. The regimens have been well-tolerated in the women. Eight participants have delivered and seven of the newborns have tested negative for HIV. Test results for the one remaining baby are pending. All infants were born without abnormalities.

Concerns were raised by a Swiss study of 37 HIV-positive pregnant women. Forty-three percent received a protease inhibitor-containing regimen. While the mothers experienced no unexpected or life-threatening adverse events, of the 30 infants born to date, 33% were premature. There were three serious adverse events among the newborns: two infants experienced non-life-threatening cerebral hemorrhages and one had a rare birth defect that caused a malformation in the bile tract. The rate of vertical transmission was low with one HIV-positive infant identified.

The sample size of this study was small, some of the women were IV drug users (which contributes to premature births), and there was no control group. Also there was no adjustment for the CD4 count and disease stage of the mother, which may be important risk factors for problems at birth. Since women on combination therapy treatment are more likely to have lower CD4 counts and more advanced disease, the increase in premature births may be because the women are sicker, not because of therapy. Nonetheless, the results of the Swiss study underline the potential risks to the newborn of combination therapy. Four NIH-sponsored ACTG trials on protease inhibitor use in pregnant HIV-positive women recently were put on temporary hold after it was determined that out of 11 infants born thus far, four were delivered prematurely. It is not clear if the premature births in these trials are due to antiretroviral therapy, the severity of maternal HIV disease or other risk factors. Ongoing reviews are evaluating how these factors may contribute to premature births. The trials will probably reopen with revised entry criteria to exclude women at high risk for premature delivery. In the meantime, NIH officials recommend that pregnant women on combination therapy continue their regimens as prescribed by their physicians.

The Breast-Feeding Dilemma

In industrialized countries, it is not recommended that HIV-positive women breast-feed their infants, as this is a known route of vertical transmission. However, breast feeding continues in many parts of the developing world due to lack of affordable and safe infant formulas. Breast-feeding can provide protection against diarrhea, respiratory disease and malnutrition. Mothers who do not nurse their infants may be stigmatized in their communities. Unfortunately, the number of infants infected by breast milk worldwide is estimated at a staggering 273,000 each year, according to the CDC.

Recent data from Africa, presented in Geneva, indicate that the risk of vertical transmission from breast milk increases with the duration of time. It is the norm for women in developing countries to nurse for an average of two years. One possible way to balance the risks and benefits of breast feeding is to wean the infants at four or six months, thereby reducing the risk. Another option is to provide breast milk alternatives. The Joint United Nations Programme on AIDS (UNAIDS) is launching projects in developing countries to provide a short course treatment of AZT to pregnant HIV-positive women to reduce the risk of prenatal transmission. The projects will also provide counseling and formula, if possible, to women who opt to bottle-feed to reduce the risk of transmission after birth.

Jill Cadman is the associate editor of GMHC's Treatment Issues, and also serves on the CRIA board of directors.

Back to CRIA Update Fall 98 Contents Page

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by AIDS Community Research Initiative of America. It is a part of the publication CRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.
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HIV/AIDS Resource Center for Women
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