PHASE-I II STUDY OF PENTOXIFYLLINE WITH ZIDOVUDINE ON HIV-1 GROWTH INAIDS PATIENTS/

Tumor necrosis factor-alpha (TNFalpha), a potential regulator of HIV-1 replication, is involved in the progression of AIDS and associated di sorders such as muscle wasting, fever and gastrointestinal problems. H IV-seropositive patients were assigned to receive zidovudine (ZDV; 100 mg 4-5 times/d) alone (n = 14), pentoxifylline (PTX; 400 mg every 8 h ), a drug known to block TNFalpha release (n = 7), or PTX and ZDV (n = 11) for 12 weeks in a prospective, open-label study. Weekly complianc e checks and biweekly blood and 24-h urine samples were obtained for i mmunological assessments. Baseline TNFalpha levels were elevated in al l study patients, independent of disease stage. There were no apprecia ble differences in immunologic variables (CD4 counts, total and unboun d p24 antigen, TNFalpha, beta2-microglobulin, and urinary neopterin le vels) between groups. The mean HIV-1 viral load, as measured by a quan titative polymerase chain reaction technique, was 1.9-fold above basel ine values after 12 weeks of ZDV and PTX compared with 8- to 9-fold gr eater levels in patients given either agent alone (p < 0.05). TNFalpha levels correlated with viral load (r = 0.67; p < 0.0001) in patients given the combined drug regimen. Virological evidence of lack of progr ession in AIDS patients suggests the beneficial use of ZDV and PTX in delaying progressive HIV-1 disease compared with each drug alone.