Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis.

Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long- term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving anti-viral immunity. In particular, treatment with nucleoside analogues was found to increase CD40L (CD154) levels, an inducible molecule expressed on activated-T lymphocytes. The present study investigated potential immunostimulatory effects of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving either ante- and post-natal therapy to reduce transmission rate. To this end, we analysed CD40L expression in unstimulated lymphocytes from peripheral blood samples of uninfected infants vertically exposed to HIV and subjected to ART. The CD45 panleucogating strategy was applied in flow cytometry to analyse the lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found an increased CD154 expression on both CD4- and CD8-lymphocytes in ART-treated infants, compared to the controls. CD154 was apparently functional, since the expression of CD86 on monocytes was enhanced, moreover, the inhibition of CD40/CD40L interaction produced down-modulation of CD86. From these results, we conclude that CD4 and CD8 lymphocytes of HIV-exposed non infected infants, who have been exposed to antiretroviral drugs in foetal and early life, display enhanced CD154 expression and co stimulatory activity.