Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course antiretroviral treatment for prevention of maternal-infant transmission

T-helper cell responses to HIV have been associated with protection against maternal-infant HIV transmission in the absence of antiretroviral treatmen t, but the effects of antiretroviral treatment, now widely used for prevent ion, on development of these cell-mediated responses is unknown. We tested whether development of T-helper cell responses to HIV and other antigens wo uld be affected by exposure to short-course regimens of zidovudine-lamivudi ne (ZDV-3TC) given to prevent maternal-infant HIV transmission. Cord blood samples were collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in which they were treated with regimens of ZDV-3TC and fr om 29 infants whose HIV-infected mothers were not treated with any antiretr oviral drugs. T-helper cell reactivity to HIV envelope peptides and other a ntigens was measured in vitro using a sensitive culture supernatant titrati on assay based on IL-2-dependent proliferation. Infants in the clinical tri al were followed to 18 months to determine their HIV infection status, and venous blood samples were re-tested at 4.5 and 9 months for T-cell reactivi ty to HIV. HIV-stimulated T-helper cell reactivity in cord blood was detect ed 10-fold less frequently among those exposed to antiretroviral prophylaxi s (2.4%) than among those unexposed (24.1%) (P = 0.007). Reductions in HIV- stimulated responses in cord blood occurred despite detectable HIV RNA (mea n 3.38 standard deviation 0.76 log(10) copies per ml) at delivery among tre ated women and occurred independent of treatment duration. Our results sugg est that short-course antiretroviral treatment given to prevent maternal-in fant HIV transmission may attenuate HIV-stimulated T-cell memory responses in the neonate.