Charles John Palenik, MS, PhD, MBA
Pediatric cases of AIDS involve children younger than 13 years of age. The cumulative number of cases reported in the United States through 2002 was 9,300. The number diagnosed annually has decreased markedly from 952 cases in 1994 to 92 children in 2002. Because of improving testing methodology, the immune status of infants born to HIV-positive mothers can now be determined very soon after birth.
HIV can be present in the blood of infected women. There is potential for the virus to enter the bloodstream of a developing fetus. The placenta separates the two bloodstreams, which, when intact, prevents exchange of cells, but not required nutrients. However, during the third trimester, small defects and tears can develop in the placenta. The result is that cells from the mother's blood can enter the fetus. During birth, the neonate often comes into intimate contact with or even swallows the mother's cervical-vaginal secretions or blood commonly associated with delivery. Multiple studies indicate that mother-to-child transmission of HIV occurs in 25 percent of cases.
In industrialized countries, three common measures are used to decrease infection of fetuses or the newborn. The three interventions include 1) highly active anti-retroviral therapy (HAART, combination therapies), 2) cesarean-section birth, and 3) formula feeding instead of breast milk. The combined effect causes viral replication in the mothers to diminish significantly, reducing mother-to-child transmission from 25 percent to 1 to 2 percent. In developing nations, HAART and complex anti-retroviral regimens are unavailable, and the avoidance of breastfeeding is not a realistic option. However, a combination of short-term and single-drug doses could prove preventive.
Administration of zidovudine (AZT, a nucleoside reverse transcriptase inhibitor) during weeks 32 through 36 of pregnancy is often paired with a single dose of nevirapine (non-nucleoside reverse transcriptase inhibitors, or NNRTI) to create a regimen that reduces the risk of peripartum transmission (Coovadia H. Anti-retroviral agents — how best to protect infants from HIV and save their mothers from AIDS. N Eng J Med 351:289-292, 2004). However, if breastfeeding occurs, the risk of transmission by 18 to 24 months remains as high as 15 to 25 percent.
Zidovudine is chemically similar to thymidine, a building block of DNA. HIV reverse transcriptase enzymes use thiamine to build proviral DNA that is incorporated into the host cell's genome. Incorporation of zidovudine instead of thymidine inactivates growing DNA molecules. Nevirapine binds to viral reverse transcriptase enzymes, preventing them from functioning. Thus, nevirapine prevents HIV from entering the nucleus of healthy T-cells and taking charge of cellular metabolism. Both drugs prevent cells from being infected and producing new virus. The effect is that the relative amount of the virus in the body decreases.
A single dose of nevirapine is added to a course of zidovudine — beginning at 28 weeks of pregnancy in women that do not breastfeed. It can achieve results equivalent (1.1 percent transmission rate) to the best results from any other drug regimen. A single dose of nevirapine is frequently given to newborns shortly after birth. A course of zidovudine alone can only reduce mother-to-child transmission of HIV to 6.5 percent.
Use of anti-retroviral agents in the prevention of mother-to-child transmission is not without concern. Drugs used could become less efficacious in subsequent pregnancies and in subsequent clinical management of infection in mothers and infants, despite prophylaxis. The possibility of resistant mutants forming also is a concern, especially with the use of nevirapine.
Nevirapine passes readily from the mother's bloodstream, through the placenta, and into the fetus. This can protect against infection. However, there are risks to the mother and to the developing fetus. Nevirapine can cause other medications to be less effective and increase their side effects. The most common side effect of nevirapine is a skin rash that can be serious. Hepatotoxicity has been noted in HIV-positive people. Women with low T-cell counts (250 per cubic millimeter) are at increased risk for liver problems, especially during the first six weeks of treatment.
Of the estimated 700,000 children who were infected in 2003, about 315,000 were infected through breastfeeding. Improving access to anti-retroviral agents in developing countries could prevent some cases of mother-to-child transmission of HIV.
Dr. Charles John Palenik is an assistant director of Infection Control Research and Services at the Indiana University School of Dentistry. Dr. Palenik has authored numerous articles, book chapters, and monographs, and is the co-author of the popular Infection Control and Management of Hazardous Materials for the Dental Team. He serves on the Executive Board of OSAP, dentistry's resource for infection control and safety. Questions about this article or any infection-control issue may be directed to [email protected].
