Pregnant Women and HIV

Post-Partum Complications in HIV-infected Women

Study Question: Does the method of delivery affect the occurrence of clinical events in the immediate post-partum period of HIV-infected pregnant women?

Study Participants: This multi-national, European study was comprised of two matched pair investigations. In one, HIV-infected women who delivered vaginally were matched with uninfected women who also delivered vaginally. In the other, HIV-infected women who delivered through caesarean section (CS) were matched with uninfected women who delivered through CS. The study participants included 500 women who delivered vaginally (250 matched pairs) and 316 women who delivered through CS (158 matched pairs). Women admitted for medical induction of labor or emergency CS were excluded from the sample.

Study Methods: Prospective data about maternal post-partum complications were collected from HIV-infected women who delivered between 1992 and 2002 to analyze the relationship between HIV-status, method of delivery, and maternal post-partum complications.

Study Findings: Irrespective of HIV infection, overall prevalence of post-partum complications was five-fold higher in the CS delivery group than in the vaginal delivery group. No major complications were observed after vaginal delivery in either the infected or uninfected women. Post-partum fever was the only minor complication for which HIV-infected women were at significantly higher risk when compared with uninfected women. Only 3% of HIV-infected women delivering vaginally received prophylactic antibiotics.

Five major complications occurred in the HIV-infected women who delivered through CS and one major complication occurred in an uninfected woman who delivered through CS. Statistical analysis revealed that HIV-infected women who delivered through CS were at significantly increased risk for minor complications and non-significantly increased risk for major complications. Anemia, not requiring blood transfusions was the most prevalent minor complication associated with CS overall, and was more frequent among HIV-infected women.

Study Limitations: Because deliveries occurred over a ten-year period, dramatic changes occurred in the standard management of HIV infection and pregnancy over the duration of the study. These changes make it difficult to uncover any relationships between particular HIV-therapies and post-partum complications.

Lessons Learned: Elective CS for HIV-infected women does not appear to increase risk of serious maternal morbidity. In addition, vaginal delivery creates similar risk of post-partum complications in HIV-positive women. In HIV-positive women who deliver vaginally, prophylactic antibiotics are likely to reduce the risk of fever, the most common post-partum complication. HIV-infected women should be informed about the risks of post-partum complications in both vaginal and CS deliveries and be involved in decisions about how they would like to deliver.

Source: European HIV in Obstetrics Group. Higher Rates of post-partum complications in HIV-infected than in uninfected women irrespective of mode of delivery. AIDS, 2004 April: 18(6): 933-38.

HIV Seroprevalence Study Among Childbearing Women

Study Question: What are the trends in prevalence of HIV infection among childbearing women in New York State?

Study Participants: Childbearing women who lived in and gave birth in New York from 1988 to 2000. 3.43 million newborns were tested for HIV antibodies during the 13-year period.

Study Methods: Mother's HIV status was determined by HIV antibody screening of newborns. Because of cross-placental transfer of antibodies, the newborn's blood specimen tests for the mother's antibody status. The annual HIV prevalence among childbearing women was calculated by dividing the total number of HIV positive specimens by the total number of positive and negative specimens each year.

Study Findings: Trends show a steady decline in HIV prevalence among childbearing women in New York. New York City had a decline of 49% between 1988/1989 and 1998/2000, and the rest of the state showed a 24% decline. In New York City, the decrease was seen in all boroughs and most racial/ethnic subgroups. However, the decrease was not uniform in all subgroups, with African American women in the Bronx showing the smallest decline. Outside of NYC, prevalence declined 24% with most of that occurring in the mid-Hudson and NYC vicinity.

Limitations: The unlinked data limits the ability to link information so it is not possible to find duplicates or women who deliver more than once. Regions of high sero-prevalence cannot be identified more specifically than by zip code.

Lessons Learned: This study reports on the only statewide, population-based HIV prevalence data for childbearing women currently available in the U.S. Significant declines in HIV prevalence occurred among most, but not all subgroups of women. The data from this study have been used extensively in targeting resources and evaluating programs and policies directed at this population.

Source: Pulver, W.P., Glebatis, D., Wade, N., Birkhead, G.S., & Smith, P. 2004. Trends from an HIV Seroprevalence Study Among Childbearing Women in New York State from 1988 to 2000. 2004. Archives of Pediatric & Adolescent Medicine. 158, 442 - 448.

Risk of Birth Defects Associated with Nelfinavir Exposure During Pregnancy

Study Question: What does the data from the Antiretroviral Pregnancy Registry show about the risk of birth defects from a pregnant woman taking nelfinavir?

Study Participants: Records of all pregnant women exposed to nelfinavir, alone or in combination with other ARVs who were included in the database of the Antiretroviral Pregnancy Registry were analyzed. The Antiretroviral Pregnancy registry is a voluntary registry of pregnant women exposed to ARVs during pregnancy.

Study Methods: Records of all women exposed to nelfinavir were analyzed. The prevalence of birth defect was compared with the Centers for Disease Control and Prevention's (CDC) population-based surveillance system.

Study Findings: From 1997 when nelfinavir was added to the registry through July 2002, the registry had monitored 915 live births exposed to nelfinavir. 21 birth defects were reported for a prevalence of 2.3%. Nine birth defects were reported among the 301 live births exposed during the first trimester for a prevalence of 3%. This rate is not significantly different from the CDC's system which had a prevalence of 3.1%. All cases involved combination therapy with exposure to other ARVs. No pattern was found among the birth defects that might suggest a common etiology.

Limitations: The sample size is small and could detect a doubling of the risk of birth defects, but not an increase in rate of specific defects. The data is collected prospectively. Retrospective reports of birth defects are not included so an underreporting is possible. Reporting is from obstetricians so that defects that are found later by pediatricians may not be reported.

Lessons Learned: Because ARV therapy is recommended for all HIV-infected pregnant women to reduce viral load and decrease the risk of perinatal transmission, information on the effects of ARV exposure during pregnancy is critical. The results of this study suggest that the overall prevalence of birth defects among infants exposed to nelfinavir is not significantly different from the CDC's birth defect surveillance system.

Source: Covington, DL, Conner, S.D., Doi, P.A. Swinson, J., and Daniels, E. 2004. Risk of Birth Defects Associated with Nelfinavir Exposure During Pregnancy. Obstetrics & Gynecology. 103, 1181 - 1189.

Resistance Testing in Pregnancy

Study Question: Can the use of genotypic resistance testing (GT) during pregnancy be a helpful indicator for choice in ARV prophylaxis to reduce perinatal transmission of HIV?

Study Participants: 50 HIV-infected pregnant women, with a mean age of 30 years. 25 (50%) were Black, 15 (30%) were Hispanic, and 10 (20%) were African immigrants.

Study Methods: The study entailed chart review of 50 consecutive HIV-infected pregnant women who received antenatal care between July 2000 and July 2002. Data used from the medical records included demographics, CD4 count and HIV viral load, prior and current antiretroviral exposure, and results of the GT.

Study Findings: 45 of 50 women had GT results. 11 women had no mutations identified, and 34 women had either a major or minor mutation in reverse transcriptase and/or protease genes. In total, 11 women (24%) had a major resistance mutation to one of the three antiretroviral classes. Six women (13%) had a major NRTI mutation, 8 women (18%) had a major NNRTI mutation, and two women (4%) had a major PI mutation. Three patients had both major NRTI and NNRTI mutations, and two patients had both major NRTI and PI mutations. All patients with major mutations indicated resistance to zidovudine, lamivudine, and/or nevirapine, the drugs most frequently used as ARV prophylaxis to reduce mother-to-child transmission of HIV.

Eleven (48%) of 23 ART experienced patients had a major mutation identified, while 0 (0%) of 22 ART naïve patients had a mutation identified; this result was highly significant (p < 0.001). There was also a significant difference (p < 0.003) between patients who were on ART at the time of testing and had major mutations (6 of 9 women, or 67%), and patients with major mutations who were not on ART at the time of GT (5 of 36 women, or 14%).

Limitations: The authors expressed concern that only 24% of women included in the study were taking ART at the time of GT. Within the population of ART-experienced patients, detection of genotypic mutation might have been hindered due to varying lengths of time since ART discontinuation. The authors emphasize that interpretation of resistance results is dependent on each patient's history of ART use.

Lessons Learned: Genotypic resistance testing can be an important indicator in determining optimal ARV prophylaxis regimens during pregnancy, especially among patients with current or prior ART use. 48% of patients with ART exposure demonstrated resistance to at least one of the three drugs used to reduce perinatal transmission, which suggests that GT should be performed routinely on HIV-infected pregnant women who have prior antiretroviral drug use.

Source: Shah, S.S., Crane, M., Monaghan, K., McGowan, J.P. Genotypic resistance testing in HIV-infected pregnant women in an urban setting. International Journal of STD & AIDS, 2004 Jun; 15: 384-387.

Pre-and Postpartum Antiretroviral Choices among HIV-Infected Pregnant Women

Study Question: What choices do pregnant women with HIV make about ARV therapy during pregnancy and the postpartum period?

Study Participants: A random sample of 57/174 pregnant women enrolled in an outpatient HIV clinic between January 1, 200 and December 31, 2002.

Study Methods: A retrospective chart review gathered data on demographics, CD4+ cell count, HIV RNA level, ARV experience, and ARV choices during pregnancy and post-partum.

Study Findings: Fifty-three percent of the women were ARV-experienced and 32% were on HAART at the time of pregnancy diagnosis. 46% were ARV naïve. Of the 35 women who started ARV regimens during pregnancy, 40% were placed on HAAART and 60% on zidovudine monotherapy. Seven of 9 women who did not meet the criteria for ARV treatment for nonpregnant adults chose to remain on their HAART regimens postpartum.

Limitations: This sample may differ from other pregnant populations because most women had relatively high CD4+ counts and low HIV RNA levels. The small sample size from a limited geographic region may not be representative of pregnant women with HIV infection.

Lessons Learned: Women who initiate HAART during pregnancy should be considered a unique population when studying long-term ARV risks and benefits. Larger studies with wider geographic variation are needed to determine if the findings of this study are consistent across diverse populations.

Source: Ejedepang-Koge, I, Theall, K and Clark, R. Pre-and Post-Partum Antiretroviral Choices Amolng HIV-Infected Pregnant Women, JAIDS 35 (4) 1 April 2004: 428-429.