354 Treatment, Immunological Changes, and Pregnancy Outcome S. Fiore*1, M.-L. Newell1, D. Trabattoni2, V. Savasi2, C. Tibaldi3, C. Lanzani2, V. Conserva2, E. Ferrazzi2, M. Clerici2 1Univ Coll of London, UK; 2Univ of Milan, Italy; and 3Univ of Turin, Italy
Background: It has been shown that type 2 cytokines increase and type 1 cytokines decrease during normal pregnancy, and that weak type 2 cytokine production may adversely affect pregnancy outcome. Progression of HIV infection is also suggested to be associated with a type 1-to–type 2 shift, and antiretroviral therapy (ART) might reverse this immunological impairment. ART treated HIV-infected women are at increased risk of premature delivery. We investigated cytokine production in HIV-infected pregnant women and the association with ART and pregnancy outcome.
Methods: Mitogen- and gp160 (env)-stimulated IL-2 (Type 1), IL-10 (Type 2) and TNF alfa production was determined in 30 women 3 times during pregnancy by ELISA assays; mitogen- and env-stimulated intracellular cytokine concentration was studied in CD4+ or CD8+ cells by FACS; cytokine-specific mRNA was quantified by PCR; and mitogen- and env-stimulated CTL were analyzed using IFN-g Elispot assays. Results were related to anti-retroviral therapy, maternal CD4 count, RNA viral load and delivery details.
Results: Twenty-nine (29)/30 women were on ART before pregnancy (none received monotherapy). Twenty-four (24) women on combination ART stopped treatment before the 14th week of pregnancy. Eleven (11) women were treated with PI-including ART. One (1) woman with AIDS died at 27 weeks gestation (GA); 9 had pregnancy complications including: premature rupture of membranes (2), premature labour before 37 GA (2), severe IUG (2), intrauterine fetal death (1), and HELLP syndrome (2). All these 9 women were treated with PI-including ART. ENV-stimulated IL 2 production was significantly increased (p = 0.03) in the 9 women showing pregnancy complications. TNF alfa was reduced and HIV specific IL-10 was greatly diminished in these women, suggesting a degree of ART-associated functional immune reconstitution which was not seen in uncomplicated pregnancies.
Conclusions: HIV disease and pregnancy may similarly impact on the immune environment, both stimulating a Type 2 response. Favourable immunomodulation induced by ART provides significant benefit in terms of HIV disease, but may be counterproductive in terms of successful pregnancy outcome.
