Pregnancy was associated with a significantly reduced risk of HIV disease progression in a cohort of HIV-infected American women on highly active antiretroviral therapy (HAART), according to the findings of a study published in the October 1st edition of the Journal of Infectious Diseases.
During the pre-HAART era, studies conducted in developed and developing countries on the effect of pregnancy on HIV disease progression provided contradictory results. Some studies have suggested that becoming pregnant accelerates the progression of HIV disease.
It is not clear whether the reported differences between developed and developing countries might be a reflection of the differences in the biology and epidemiology of HIV/AIDS transmission and standards of healthcare.
In developing countries, pregnant women are at an increased risk of infection with a legion of other co-endemic diseases such as malaria and gastrointestinal nematode infections which have a clinical impact on HIV/AIDS progression.
During the HAART era, there has been a significant reduction in HIV-related disease and deaths possibly due to HAART-mediated viral suppression and immunologic recovery in patients. An increasing number of HIV/AIDS patients in developing countries now have access to HAART as a result of national and international initiatives.
The relationship between pregnancy and HIV disease progression in HIV-infected women on HAART remains unknown in both developed and developing countries. A team of US investigators addressed this issue in a cohort of American women in Nashville, Tennessee.
The study site was Vanderbilt University Medical Center where the women received obstetrical care before March 1999 and at the Comprehensive Care Center where they received prenatal care after March 1999.
Study participants were all HIV-infected women who received HIV care on more than one outpatient clinic visit between January 1997 and December 2004, who had either a CD4 cell count and or HIV-1 RNA load at baseline, and who met the study criteria.
HIV disease progression was defined as the occurrence of an AIDS-defining event based on 1993 CDC criteria or death.
Of 759 women who met the inclusion criteria, 139 (18%) had had a pregnancy, and 540 (71%) had received HAART. There were 174 pregnancies during the study period. Pregnant women were more likely than non-pregnant women to receive HAART. There was no difference in HAART duration by pregnancy status.
Eleven pregnant (8%) and 149 non-pregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4 lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression, pregnancy was associated with a decreased risk of disease progression.
In a matched-pair analysis of 81 pregnant women matched to 81 non-pregnant women according to age, baseline CD4 lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01–0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19–1.00]; P=.05) the pregnancy event.
When the end-point was either an AIDS-defining event alone or death alone, the event rate was significantly lower in pregnant women (P = 0.003 and P
Age did not have any impact on the advantage provided by pregnancy in terms of the lower risk of disease progression. However, women who had more than one pregnancy tended to have a lower risk of disease progression by comparison with women with one pregnancy (P = 0.08).
Finally, the difference in disease progression between non-pregnant and pregnant women was most remarkable in women with CD4 cell counts between 201 and 350 cells/mm3 (P = 0.01). This was confirmed by another statistical model.
After controlling for the effect of confounding variables inherent in the experimental design including the possibility that healthier women were more likely to get pregnant, pregnancy was consistently associated with a lower risk of disease progression.
These are exciting results for clinical investigators and good news for HIV-infected women who get pregnant and are on anti-HIV therapy. However, there is need for additional studies to unravel the mechanisms underlying the possible protective effect of pregnancy against disease progression. Studies which focus on the interaction between anti-HIV therapy and immunity during pregnancy might provide useful insights for future interventions in HIV-infected pregnant women during the HAART era.
Tai JH et al. Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy. J. Infect Dis 196: 1044-1052, 2007.