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 evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 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 months AZT at entry), four AIDS or death events occurred in thymopentin and 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 changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.
Goldstein
G
G
Immunobiology Research Institute, Annandale, New Jersey.
Conant
M A
MA
Beall
G
G
Grossman
H A
HA
Galpin
J E
JE
Blick
G
G
Calabrese
L H
LH
Hirsch
R L
RL
Fisher
A
A
Stampone
P
P
D000328:Adult; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000187:drug effects / Q000235:genetics; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010419:Pentamidine / Q000627:therapeutic use; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models; D016305:Thymopentin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use*
D016655:HIV Core Protein p24; D015215:Zidovudine; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D016305:Thymopentin