S. Moretti et al., Combined antiviral therapy reduces HIV-1 plasma load and improves CD4 counts but does not interfere with ongoing lymphocyte apoptosis, IMMUNOPH IM, 21(4), 1999, pp. 645-665
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.