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To induce recovery of HIV-1-specific immune responses by combining immunization with antiviral chemotherapy.Forty HIV-infected patients entered a double-blind study with recombinant gp160 in combination with zidovudine or placebo. The pretreatment observation period was around 2 years and the treatment period 5 years. Eighty matched HIV-infected patients served as controls.Immune status was monitored by proliferation assays with HIV-specific antigens, mitogens and recall antigens. Viral load, CD4 cell counts, apoptosis, T-cell clonal analysis and CC-chemokine receptor (CCR)-5 status were determined.All immunized patients showed a strong and HIV-specific T-cell proliferative response. This response was related to the immunizations, and was not enhanced by the zidovudine monochemotherapy given during the first 6 months of the immunizations. The treatments did not significantly alter viral load. Potent antiviral combination therapy given to non-immunized individuals reduced their viral load but did not influence HIV-specific immune responses. There was a trend for an increased frequency of non-progression in the immunized group compared with controls. These individuals had both wild-type and mutant CCR-5 genes.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 monochemotherapy. Even intensive chemotherapy alone did not restore HIV-specific immunity and immunization alone did not influence viral load. This suggests that combinations of intensive chemotherapy with specific HIV immunization would result both in viral load reduction and improved immune responses to HIV.