Combined antiviral therapy reduces HIV-1 plasma load and improves CD4 counts but does not interfere with ongoing lymphocyte apoptosis.
The progression of HIV-1 disease appears associated with an unregulated Fas-mediated apoptosis of lymphocytes that involves the activation of ICE protease and ceramide generation and antiviral therapy may not be fully effective in the absence of a relevant impact on apoptosis. Six drug-naive HIV-1-infected symptomless patients with advanced immunodeficiency were treated with combined AZT and ddl for 4 months; plasma HIV-1 RNA levels, the counts of CD4 cells, CD4 and CD8 apoptotic lymphocytes, Fas-positive cells and ICE-positive cells, and intracellular ceramide levels were 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 lymphocytes, 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 treatment on plasma viral load and CD4 counts and the lack of any effect on the process of lymphocyte apoptosis. We suggest to use the measurement of apoptotic lymphocytes as a surrogate marker to predict, in combination with viral load and CD4 counts, a large proportion of the clinical effect of antiviral therapy.
Moretti
S
S
Department of Experimental Medicine, University of L'Aquila, Italy.
Alesse
E
E
Marcellini
S
S
Di Marzio
L
L
Zazzeroni
F
F
Parroni
R
R
Famularo
G
G
Boschini
A
A
Cifone
M G
MG
De Simone
C
C
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D020170:Caspase 1 / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology; D015215:Zidovudine / Q000627:therapeutic use; D019014:fas Receptor / Q000096:biosynthesis / Q000097:blood
D019380:Anti-HIV Agents; D002518:Ceramides; D019014:fas Receptor; D015215:Zidovudine; D020170:Caspase 1; D016049:Didanosine