Pregnant Women and HIV

Pharmacokinetics and Safety of Stavudine in HIV-Infected Women and Their Infants

Study Question(s): Is stavudine (d4T) a safe medication for HIV-infected women and their infants?

Study Participants: 14 HIV-infected women and their newborn infants. Women were zidovudine (ZDV)-intolerant or refusing.

Study Methods: Women were enrolled in the study at 17-36 weeks gestation. Women were split into two groups that both received d4T and lamivudine (3TC) beginning at study enrollment and continuing to the start of active labor. However, at the start of active labor, women in group 1 (n=4) received an IV loading dose of d4T, while women in group 2 (n=10) received an oral dose of d4T that was then repeated every 12 hours. Both groups received 3TC during labor. All infants received 3TC and ZDV for the first 6 weeks of life. At weeks 1 and 6, infants received a single oral dose of d4T. Blood was obtained from the mothers at the start of the treatment and during labor for pharmacokinetic evaluation. Blood was also taken from the infants upon delivery.

Study Findings: None of the women had severe or life-threatening drug-related toxicities during the study. Likewise, no infants exhibited toxicities that warranted discontinuing the study or drug use. No infants were HIV-infected. The d4T pharmacokinetics during the antenatal period were not significantly different from the d4T pharmacokinetics during labor. Similarly, umbilical cord and maternal plasma concentrations were not significantly different from one another. Furthermore, the oral clearance of d4T in infants was significantly greater at week 6 than it was at week 1.

Limitations: This study could not show the effect of d4T on HIV viral load reduction, because 10 of the 14 women in the study were already receiving d4T when they entered the study. Additionally, as a phase 1/2 study, this study was not able to address the efficacy of d4T for preventing perinatal HIV transmission.

Lessons Learned: The major finding in this study is that d4T, in combination with 3TC, was well-tolerated by pregnant women. Therefore, d4T can be seen as a potential alternative to ZDV when ZDV is refused due to potential toxicity.

Source: Wade, NA., Unadkat, JD., Huang, S., Shapiro, DE., Mathias, A., Yasin, S., Ciupak, G., Watts, DH., Delke, I., Rathore, M., Hitti, J., Frenkel, L., Samelson, R., Smith, ME., Mofenson, L., and Burchett, SK. Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332. Journal of Infectious Diseases. 2004 December; 15;190(12). 2167-74.

HIV Infection and Zidovudine in Childbearing Women

Study Question(s): Have New Jersey's policy and programs been successful in reducing mother-to-child transmission of HIV infection over the past decade? Has there been a decrease in HIV infection rates among childbearing women and an increase in zidovudine use to prevent perinatal HIV transmission?

Study Participants: A total of 372,305 women were included in this study. Participants were all women who gave birth from July through September between 1990 and 2002 in New Jersey.

Study Methods: Rates of HIV infection in women and use of ZDV to prevent mother-to-child transmission of HIV infection were assessed using data from anonymous HIV screening of all babies born during the study time period. HIV antibody testing was performed on excess blood from heel stick papers obtained during screening for inborn errors of metabolism. Beginning in 1994, specimens that were found to be HIV positive were tested for the presence of ZDV.

Study Findings: Overall, there was a 55% decrease in the percentage of childbearing women who tested positive for HIV from 1990 to 2002. HIV infection rates decreased among childbearing women in all age groups under age 35, but increased in women 35-39 years of age. These women (35-39 years) had the lowest rates of HIV infection at baseline and now have higher rates (0.33) than younger women. Rates of HIV infection among childbearing women were highest among black non-Hispanic women, followed by Hispanic women and white non-Hispanic women -and decreased in all groups. Although the decline was greatest among black non-Hispanic women, disparities in infection rates persist. Lastly, the use of ZDV in HIV-positive childbearing women increased substantially from 13.3% in 1994 to 88.5% in 2002.

Limitations: Decreases in HIV prevalence among women of childbearing age may be related to the decisions of HIV-infected women not to become pregnant or carry to term. Because this is an anonymous unlinked survey, the study cannot explain the increase in HIV rates among older women or reasons why HIV positive women did not receive/take ZDV during pregnancy.

Lessons Learned: Decreased HIV prevalence among childbearing women coupled with increased use of zidovudine marks success for New Jersey's prevention policy. Perinatal infection rates have decreased from 21% to 1993 to less than 2% in 2002. In addition to policy for mandatory HIV counseling and testing, much of this change can be attributed to widespread prevention and education programs directed to the public and healthcare providers, including education about the use of ZDV. Despite substantial success, clinicians, healthcare providers, and educators must continue to target prevention efforts to populations of childbearing women at the greatest risk of HIV infection.

Source: Sia, J., Paul, S., Martin, RM., & Cross, H. HIV infection and zidovudine use in childbearing women. Pediatrics. 2004 December; 114(6). 707-12.

Expanded Practice Recommendations for Prenatal and Perinatal HIV Testing

This article provides a list of recommendations made by the Committee on Obstetric Practice concerning prenatal and perinatal HIV testing in order to reduce the rates of perinatal HIV transmission.

Background: Although serious advances have been made in decreasing vertical transmission of HIV, about 300 infants with perinatally acquired HIV infection were born in the United States in the last year. This figure represents a rate of vertical transmission that is down to 2%. However, in an effort to lower the rate of vertical transmission even more, the American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice has developed the following recommendations.

Recommendations:

	Follow an opt-out prenatal HIV testing approach wherever possible
	Repeat offer of HIV testing in third trimester to women at especially high risk for HIV infection
	Use conventional HIV testing for women who are candidates for third-trimester testing
	Use rapid HIV testing in labor for women with undocumented HIV status
	If rapid HIV test result is positive, initiate antiretroviral prophylaxis without waiting for the results of the confirmatory test

Source: ACOG Committee on Obstetric Practice. ACOG committee opinion number 304, November 2004. Prenatal and perinatal human immunodeficiency virus testing: expanded recommendations. Obstetrics and Gynecology. 2004 November; 104(5 Pt 1). 1119-24.