SAFETY AND EFFICACY OF THYMOPENTIN IN ZIDOVUDINE (AZT)-TREATED ASYMPTOMATIC HIV-INFECTED SUBJECTS WITH 200-500 CD4 CELLS MM3 - A DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL/

Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluat ed in a double-blind, randomized, placebo-controlled trial of zidovudi ne (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infec ted subjects with 200-500 CD4 cells/mm(3) at entry. The 352 subjects w ere prestratified by prior AZT use into stratum I (235 subjects, >6 mo nths AZT at entry) and stratum II (117 subjects, less than or equal to 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p 24, serum immune complex dissociated (ICD) p24, and safety variables w ere evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different nt clinic al outcomes, with a statistically significant treatment-by-s tratum interaction. In stratum I(mean, 16 months AZT at entry) two AID S or death events occurred in thymopentin and 10 in placebo recipients {p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (C I), 1.1 to 22.2]}. There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001 ; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 mont hs AZT at entry), four AIDS or death events occurred in thymopentin an d none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79 ). The treatment groups did not differ significantly with respect to c hanges in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experience d placebo-treated subjects had relatively high progression rates to AI DS or death and to ARC, AIDS, or death, and these rates were reduced b y thymopentin treatment. In contrast, placebo-treated subjects with li ttle prior AZT experience had low progression rates; these were not si gnificantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.