Combined antiviral therapy reduces HIV-1 plasma load and improves CD4 counts but does not interfere with ongoing lymphocyte apoptosis

The progression of HIV-1disease appears associated with an unregulated Fas- mediated apoptosis of lymphocytes that involves the activation of-ICE prote ase and ceramide generation and antiviral therapy may not be fully effectiv e in the absence of a relevant impact on apoptosis. Six drug-naive HIV-l-infected symptomless patients with advanced immunodefi ciency were treated with combined AZT and ddl for 4 months; plasma,HIV-l RN A levels, the counts of CD4 cells, CD4 and CD8 apoptotic lymphocytes, Fas-p ositive cells and ICE-positive cells, and:intracellular ceramide levels wer e measured at base-line:and after 7, 45 and 120 days of treatment. There was a prompt reduction in plasma viremia and a secondary increase in CD4 counts, but the treatment had no impact on apoptotic CD4 and CD8 lympho cytes, Fas-positive-cells and ICE-positive cells, and on the intracellular levels of ceramide. A discrepancy exists between the positive impact of combined AZT and ddl tr eatment on plasma viral load and CD4 counts and the lack of any effect on t he process of lymphocyte apoptosis. We suggest to use the measurement of ap optotic lymphocytes as a surrogate marker to predict, in combination with v iral load and CD4 counts, a large proportion of the clinical effect of anti viral therapy.