INDUCTION OF SPECIFIC T-CELL RESPONSES IN HIV-INFECTION

Objectives: To induce recovery of HIV-1-specific immune responses by c ombining immunization with antiviral chemotherapy. Design: Forty HIV-i nfected patients entered a double-blind study with recombinant gp160 i n combination with zidovudine or placebo. The pretreatment observation period was around 2 years and the treatment period 5 years. Eighty ma tched HIV-infected patients served as controls. Methods: Immune status was monitored by proliferation assays with HIV-specific antigens, mit ogens and recall antigens. Viral load, CD4 cell counts, apoptosis, T-c ell clonal analysis and CC-chemokine receptor (CCR)-5 status were dete rmined. Results: All immunized patients showed a strong and HIV-specif ic T-cell proliferative response. This response was related to the imm unizations, and was not enhanced by the zidovudine monochemotherapy gi ven during the first 6 months of the immunizations. The treatments did not significantly alter viral load. Potent antiviral combination ther apy given to non-immunized individuals reduced their viral load but di d not influence HIV-specific immune responses. There was a trend for a n increased frequency of non-progression in the immunized group compar ed with controls. These individuals had both wild-type and mutant CCR- 5 genes. Conclusion: The results clearly show that restoration of HIV- specific T-cell immunity occurs after immunization with the HIV gp160 antigen and is not influenced by the addition of antiviral monochemoth erapy. Even intensive chemotherapy alone did not restore HIV-specific immunity and immunization alone did not influence viral load. This sug gests that combinations of intensive chemotherapy with specific HIV im munization would result both in viral load reduction and improved immu ne responses to HIV.