Decreased CD8 cell-mediated viral suppression and other immunologic characteristics of women who transmit human immunodeficiency virus to their infants.

CD8 T cell function, lymphocyte surface phenotype, serum markers of immunologic activation, and viral burden were assessed in 75 human immunodeficiency virus (HIV)-infected pregnant women, including 9 who transmitted infection to their infants. Serial studies during and after pregnancy showed no significant differences in levels of cell-surface or serum activation molecules in transmitting compared to nontransmitting mothers, with the exception of a postpartum increase in tumor necrosis factor alpha in transmitting women. The transmitting women had a median plasma viral load of 65,516 RNA copies/mL at delivery versus 5139 in nontransmitting women. During the third trimester, the CD8 cells of 81% of the nontransmitting and 44% of the transmitting mothers suppressed HIV production in vitro by >50%. Women with <50% suppression had a 3.4 times greater risk of transmitting HIV to their infants. CD8 suppression and viral load were interrelated, but when either CD4 percent or AZT use was controlled for, suppression was still significant.

Immunologic activation during pregnancy: serial measurement of lymphocyte phenotype and serum activation molecules in HIV-infected and uninfected women.

Immunologic alterations occur during pregnancy, but the effect of pregnancy on HIV infection is controversial. We characterized some of the immunologic alterations with potential to influence HIV disease in 99 infected and 46 uninfected women during pregnancy and up to 6 months post-partum. Immunophenotyping to quantitate the major lymphocyte subsets and determine expression of activation and adhesion molecules on T cells was performed using 3-color staining and laser flow cytometry. Serum neopterin, beta 2-microglobulin, and tumor necrosis factor-alpha (TNF alpha) were quantitated using commercial immunoassays. HIV + pregnant women were compared to uninfected pregnant subjects and to reference ranges established on healthy, HIV-seronegative non-pregnant female controls. Both CD4 and CD8 T cell subsets were increased in HIV-negative pregnant women compared to non-pregnant controls. In HIV-infected pregnant women, CD4 T cells were low and CD8 cells were elevated compared to HIV-negative pregnant and non-pregnant women. Levels of subsets were stable during pregnancy and postpartum in both groups of women. Evidence of peripheral immune activation was found during the later stages of pregnancy. Increases in HLA-DR and CD38 activation antigens on CD8 cells, serum neopterin and beta-2-microglobulin were seen during pregnancy in HIV-negative women. These correlates of immune activation were increased in HIV-infected pregnant women and increased further during pregnancy, paralleling changes seen in uninfected pregnant women. These immunologic alterations may directly or indirectly enhance viral replication, impacting the long-term course of HIV disease.