Findings from the Pediatric AIDS Clinical Trials Group Protocol 076 (PACTG 076) published in 1994 in the New England Journal of Medicine¹ showed that when women and their infants took zidovudine (AZT, Retrovir), this resulted in a significant reduction in perinatal transmission of HIV.

Over the next 2 years, subsequent studies demonstrated, for the first time, a survival benefit for people living with HIV who took combination antiretroviral therapy. Since then, the treatment of HIV-infected pregnant women has been based on the belief that therapies of known benefit to women should not be withheld unless there are known adverse effects on the mother, fetus or infant and these effects outweigh the benefit to the woman. Pregnancy itself does not appear to accelerate HIV progression or increase maternal mortality when appropriate prenatal care occurs and women have access to antiretroviral medication.^2-4 However, there is some data on the effect of HIV and related therapies on pregnancy outcome as it relates to prematurity, low birth weight and still birth, although the results are mixed and more study and follow-up is needed.^5-7

Preeclampsia refers to the onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman.⁸ A fetal death is defined by the World Health Organization as a death prior to birth at any gestational age.⁹ In the HIV-uninfected pregnant woman, much is known about the risk factors and causes of both preeclampsia and fetal death. As HIV-infected women in their reproductive years are living longer, healthier lives due, in large part, to combination antiretroviral therapy, more of these women are considering pregnancy. Studies that show a possible association between HIV and related therapies to preeclampsia and fetal death have been limited.

In this presentation, Suy and colleagues reported on a significant increase in preeclampsia and fetal death in HIV-infected pregnant women on highly active antiretroviral therapy (HAART).

Records on all pregnant women who delivered at the Hospital Clinic in Barcelona, Spain, were reviewed from January 2001 through August 2003 to determine if there was any association between preeclampsia and/or fetal death and a number of factors, including HIV infection and HAART. During this time period, 8,295 women delivered babies of whom 82 (0.9%) were HIV infected.

Overall, the researchers found that 237 (2.9%) of the HIV-uninfected women who had delivered had preeclampsia and 40 (0.5%) had fetal death. Alarmingly, the HIV-infected women had a much higher rate of preeclampsia (11%) and a significantly higher incidence of fetal death (6.1%).

The investigators also did a retrospective review of the labor and delivery records of all HIV-infected pregnant women (472) at the same hospital from November 1985 through August 2003 (inclusive of the above analysis), and observed a startling trend.

The results were correlated to 3 distinct antiretroviral periods: 1985-1994, when none of the women were on antiretrovirals; 1994-1998, when women were on monotherapy or dual-nucleoside therapy; and 1998-2003, the HAART period (see Table).

The increased incidence of preeclampsia and fetal death in HIV-infected women was clearly associated with the HAART period, and the length of time on HAART prior to pregnancy also seemed to be associated with higher risk. The authors also noted that during the same time period, there was no mother-to-child transmission of HIV.

Incidence of Preeclampsia and Fetal Death in HIV-Infected Pregnant Women*

Dates	No. of Women	Preeclampsia Incidence	Fetal Death Incidence	Mother-to-Child Transmission Incidence
1985-1994	258	0	2 (0.8%)	12%
1994-1998	74	0	0	4%
1998-2003	140	9 (6.4%)	6 (4.2%)	0

*(The authors did not include the numbers of transmission, only the percentages.)

As women live longer with HIV, more women will and have elected to become pregnant. As clinicians caring for these women, we need to provide as much support and information as possible for them to make as informed a decision as they can. This involves encouraging women to have "planned" pregnancies with regular prenatal care, beginning early in their pregnancy. All HIV-infected women in their reproductive years should consider taking prenatal vitamins. The use of antiretroviral therapy -- what we know and don?t know -- should be discussed regularly. We can now assure women that with proper prenatal care and treatment of HIV, the risks of perinatal transmission (at least in the United States and other developed countries) is extremely low. This study helps support that fact. Obviously, continued and close follow-up of all HIV-infected pregnant women on HAART should continue, as well as other studies to evaluate the impact of HAART on pregnancy outcomes.

Footnotes

1. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med. November 3, 1994;331(18):1173-1180.

2. Minkoff H. Human immunodeficiency virus infection in pregnancy. Obstet Gynecol. April 1, 2003;101(4)797-810.

3. Minkoff H, Augenbraun M. Antiretroviral therapy for pregnant women. Am J Obstet Gynecol. February 1997;176(2):478-489.

4. Minkoff HL, Henderson C, Mendez H, Gail MH, Holman S, Willoughby A, et al. Pregnancy outcomes among mothers infected with human immunodeficiency virus and uninfected control subjects. Am J Obstet Gynecol. November 1990;163(5, Part 1):1598-1604.

5. Ellis J, Williams H, Graves W, Lindsay MK. Human immunodeficiency virus infection is a risk factor for adverse perinatal outcome. Am J Obstet Gynecol. May 2002;186(5, Part 1):903-906.

6. Brocklehurst P, French R. The association between maternal HIV infection and perinatal outcome: a systematic review of the literature and meta-analysis. Br J Obstet Gynaecol. August 1998;105(8):836-848.

7. Stratton P, Tuomala RE, Abboud R, Rodriguez E, Rich K, Pitt J, et al. Obstetric and newborn outcomes in a cohort of HIV-infected pregnant women: a report of the women and infants transmission study. J Acquir Immune Defic Syndr Hum retrovirol. February 1, 1999;20(2):179-186.

8. Cunningham FG, Lindheimer MD. Hypertension in pregnancy. N Engl J Med. April 2, 1992;326(14):927-932.

9. Procedures for coding cause of fetal death (2003 revision). Available at www.cdc.gov/nchs/about/major/fetaldth/abfetal.htm#Data%20Highlights. No abstract available.