Given the positive results of the TP1-AZT Multicenter Study (TAMS), a second stage of the study was undertaken. The goal of this second study was to confirm the therapeutic efficacy and clinical and immunologic effects of the combination of low-dose zidovudine (AZT) and thymostimulin (TP1) in a larger number of patients infected with human immunodeficiency virus (HIV) belonging to Centers for Disease Control and Prevention (CDC) group 2 (patients with asymptomatic HIV infection) and group 3 (patients with persistent generalized lymphadenopathy). A total of 248 HIV-positive patients were divided into two groups. Group A consisted of 123 CDC group 2 patients and group B consisted of 125 CDC group 3 patients. Each group was divided into two subgroups according to pharmacologic therapy. Subgroups A1 (n = 62) and B1 (n = 61) were treated with AZT (500 mg/d); subgroups A2 (n = 61) and B2 (n = 64) were treated with AZT (500 mg/d) + TP1 (70 mg/d intramuscularly for 1 week and then 70 mg intramuscularly three times per week). Clinical evaluations and routine hematochemical tests were checked every 15 days during the first month, every month during the following 2 months, and then every 3 months up to the end of the follow-up period (17 ± 3 months). In group A, a significant increase in T cells, subset CD4+, was observed in the group treated with AZT + TP1: this difference was statistically significant compared with both the pretreatment values (+7.6%, P <0.001) and the AZT-treated group (+13.5%, P <0.001). At the end of the follow-up period, a significant difference in the white blood cell (WBC) count between groups A1 and A2 was noted (+15% in group A2 [P <0.001 vs baseline values], and -28% in group A1 [P <0.001 vs baseline values and P <0.001 vs group A2]). Oral candidiasis was the only opportunistic infection observed in the group A patients. None of the patients in the two group A subgroups progressed to acquired immunodeficiency syndrome (AIDS). In group B, a significant increase in T cells, subset CD4+, was observed in patients treated with AZT + TP1; the difference was statistically significant compared with both the pretreatment values (+9.3%, P <0.001) and the AZT-treated group (+13.7%, P <0.001). In the AZT-treated group, a significant myelodepression was observed. At the end of the follow-up period, a difference was noted between groups B1 and B2 in blood cell counts, with a significant increase seen in the AZT + TP1-treated group (red blood cells, +8.1%, P <0.001; WBC, +15%, P <0.001; and platelets, +30%, P <0.001). Opportunistic infections were observed in 14 (22.9%) patients in group B1 and 9 (14.1%) patients in group B2 (relative risk ratio, 0.64; 95% confidence interval, 0.27-0.82; P <0.001). Progression to AIDS was observed in five (8.2%) patients in group B1 and two (3.1%) patients in group B2 (relative risk ratio, 0.40; 95% confidence interval, 0.22-0.70; P <0.05). These results suggest that the combination of AZT and TP1 may be useful in the early stages of HIV infection, particularly in HIV-positive patients with levels of CD4+ T cells ≥400/mm3 and 3. AZT + TP1 significantly improved cell-mediated immunity parameters and decreased the incidence of opportunistic infections. In the more advanced stages of HIV infection, AZT + TP1 may have a positive effect on immunologic and hematologic parameters and reduce the myelodepressive effect of long-term treatment with AZT.
ASJC Scopus subject areas
- Pharmacology (medical)