ANTIRETROVIRAL THERAPY REVERSES HIV-ASSOCIATED ABNORMALITIES IN LYMPHOCYTE APOPTOSIS

The objective of this study was to assess the role of anti-retroviral therapy (ART) on the susceptibility of peripheral blood lymphocytes (P BL) from HIV-1-infected individuals to activation-induced apoptosis an d in comparison with changes in CD4 lymphocyte counts. Eleven symptoma tic HIV+ patients were studied. Ex vivo apoptosis was measured in phyt ohaemagglutinin (PHA)-stimulated PBL and CD4 subsets by how cytometry, at baseline and after 1 month (4-6 weeks) and 2/3 months of ART. Six patients had extended studies of the effects of therapy to a maximum o f 21 months. Lymphocyte apoptosis was significantly elevated in HIV+ p atients at baseline (median 22% compared with 75% in HIV- risk-matched controls; P<0.05). This decreased to control levels on ART (74% at 4- 6 weeks, P < 0.01, and 62% at 8-12 weeks, P < 0.05, compared with base line). Similar changes occurred in the CD4(+) subpopulation. The decre ase in apoptosis was maintained for several months, but the effect was rapidly lost if ART was discontinued. CD4 counts showed a reciprocal relationship to changes in apoptosis. The association of changes in ap optosis with those in CD4 counts suggests a link between programmed ce ll death and lymphocyte depletion. Apoptosis reduced in some individua ls without any reduction in viral load, suggesting apoptosis may be in fluenced by factors in addition to the overall extent of HIV replicati on.