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Tuesday, January 14, 2003: TOPIC V: HORMONAL INFLUENCE ON CHANGES IN GENITAL TRACT VIROLOGICAL/IMMUNOLOGICAL PARAMETERS AND IMPLICATIONS FOR TRANSMISSION

Effect of Pregnancy

Watts, D Heather

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: March 2005 - Volume 38 - Issue - p S36-S38
doi: 10.1097/01.qai.0000167041.35311.be

Introduction

Pregnancy is associated with relative immunosuppression, as evidenced by tolerance of the fetus and increased mortality rates from viral infections such as influenza and varicella among pregnant women. The majority of HIV-1 infections among women occur during the reproductive years, and pregnancy occurs frequently among HIV-1-infected women. It is thus important to understand the potential interaction of the physiological changes of pregnancy and HIV-1 infection, and the impact on maternal health.

Plasma HIV-1-RNA Levels

Plasma HIV-1-RNA levels do not appear to increase more rapidly during pregnancy, but may rebound during the immediate postpartum period. An early study comparing the slope of HIV-RNA levels during pregnancy and during the first and second year postpartum, did not detect a difference between any of the time periods1. A report from the Ariel Project2 noted a change in the HIV-1-RNA level of −2 copies/ml a day during pregnancy compared with an increase of 6 copies/ml a day (P < 0.0001) during the first 6 months postpartum. Among women enrolled into the PACTG 185 trial comparing the efficacy of HIVIG with IgG in preventing the perinatal transmission of HIV-1 among women with CD4 lymphocyte counts below 500 cells/μl receiving nucleoside reverse transcriptase inhibitor therapy, HIV-1-RNA levels were stable during pregnancy but increased significantly, by approximately 0.5 log10 copies/ml, during the first 12 weeks postpartum, even among women on stable antiretroviral regimens3. These data suggest that HIV-1-RNA levels increase in the early postpartum period, but a lack of prepregnancy data preclude the assessment of a possible decrease in early pregnancy. In addition, further study is needed to evaluate early postpartum changes among women on stable HAART regimens and to elucidate the pathogenesis of these changes.

Genital HIV-1 RNA Levels

Many studies have evaluated the genital tract HIV-1 during pregnancy, with HIV-1 being detected in culture among 38–41%, by DNA PCR in 32–67%, and by RNA PCR in 21–45%4–10. In cross-sectional studies comparing the rates of detection of genital HIV-1 between pregnant and non-pregnant women, the three largest studies4,11,12 found an adjusted OR of detection of genital tract HIV-1 by culture or DNA PCR during pregnancy of 2.6–4.6. Two smaller studies5,6, one evaluating for HIV-1 RNA and one for DNA, did not find increased detection during pregnancy. The detection of HIV-1 by culture or DNA in the genital tract during pregnancy has been consistently associated with an increased risk of perinatal transmission9,10,13,14, whereas cell-free but not cell-associated RNA detection increased the risk of transmission in one study, but not another, although DNA detection was associated with increased transmission in both of the studies9,14. Therefore, although it is unclear whether pregnancy increases the detection of HIV-1 in the genital tract, the detection of HIV-1 by culture or DNA PCR is associated with an increase in the risk of transmission. A reduction in genital tract HIV-1 levels may account for a portion of the efficacy of antiretroviral therapy in the reduction of perinatal transmission, but further longitudinal study of genital tract detection of HIV-1 during pregnancy is needed.

Immunological Changes in Pregnancy

Pregnancy in HIV-uninfected women is associated with a relative switch from a T helper type 1 to a T helper type 2 immune response. Normal pregnancy is associated with CD8 activation, especially in the third trimester. Relative immune changes among pregnant HIV-uninfected women and HIV-infected women compared with HIV-uninfected, non-pregnant women are summarized in Table 115–18. The immune-activating effects of HIV-1 infection appear to outweigh the changes seen in normal pregnancy. These observations are consistent with epidemiological studies from developed countries that have found no increased risk of disease progression among women compared with those without an intervening pregnancy1,19,20. Studies from developing countries have been limited and difficult to interpret. More data regarding immune function in pregnancy are needed.

TABLE 1
TABLE 1:
Changes in Immune Parameters Among HIV-uninfected and HIV-infected Pregnant Women Compared with HIV-uninfected, Non-pregnant Women

Conclusion

HIV-1-RNA levels appear to be stable during pregnancy but may increase in the early postpartum period. Further study is required to determine whether this previously described increase continues to occur among women on HAART regimens, and if so, why. HIV-1 detection in the genital tract may be more frequent among pregnant women, and is clearly associated with an increased risk of transmission of HIV-1 to the infant. Whereas immunological changes occur during pregnancy that may impact HIV-1 replication, these changes appear to be outweighed by the changes seen related to HIV-1 infection, and pregnancy has not been shown to accelerate HIV-1 disease progression in the majority of studies to date. Much additional work remains to be done to understand normal genital tract physiology and immune response, factors affecting HIV-1 detection in the genital tract, and the immunological changes during pregnancy among both HIV-infected and uninfected women.

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