Antigen-specific beta-chemokine production and CD8 T-cell noncytotoxic antiviral activity in HIV-2-infected individuals.

Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8+ T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8+ T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1Bal) and beta-chemokine-insensitive X4 virus (HIV-1IIIB) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8+ T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8+ T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.

DNA immunization with HIV early genes in HIV type 1-infected patients on highly active antiretroviral therapy.

The aim of this study was to evaluate the immunological responses induced by DNA plasmids containing HIV regulatory genes administered in combination in HIV-1-infected patients with pretreatment with highly active antiretroviral treatment (HAART). The study is a double-blind, randomized, and placebo-controlled study, including 15 asymptomatic HIV-1-infected patients on stable HAART for at least 6 months and with plasma HIV RNA levels below 50 copies/ml. Ten patients received a combination of rev, tat, and nef intramuscularly (im) at weeks 0, 4, and 16 at increasing doses giving totals of 300 (100 x 3), 900 (300 x 3), and 1800 (600 x 3) micrograms DNA. Five patients received saline in the same amounts im. Antigen-specific cytotoxic T lymphocyte (CTL) levels were preserved or increased and new T lymphocyte proliferative responses were induced in the group immunized with the HIV DNA genes. No increase in antibody levels was noted. Despite a 10-fold higher vaccine dose, patients on HAART did not respond better to vaccination compared to non-HAART patients included in a previous study where the genes were administered separately. Combining the regulatory genes rev, tat, and nef in increasing doses may reduce the anticipated augmentation of HIV-specific T cell proliferative and CTL responses. Viral suppression did not seem to further improve the initial vaccine responses of patients with comparable CD4 levels.

Better preserved immune responses after immunization with rgp 160 in HIV-1 infected patients treated with highly active antiretroviral therapy than in untreated patients with similar CD4 levels during at 2 years' follow-up.

OBJECTIVE: To study the impact of effective highly active antiretroviral therapy (HAART) on the preservation of long-term CD4 memory cells induced by vaccines in HIV-1-infected patients. METHODS: Thirty HIV-1-positive patients on HAART with undetectable viral load were randomized into three groups: 10 received HIV-1 rgp160 vaccine, 10 received tetanus vaccine and 10 patients were not immunized. As controls, 10 HIV-negative volunteers were immunized with tetanus vaccine. The results were compared with an rgp160 vaccine study performed before the era of HAART on patients with comparable CD4 levels. All patients were monitored for 2 years for T-cell proliferative responses, T-cell subset levels, serum IgG and viral load. RESULTS: After 1 year all patients immunized with rgp160 had strong T-cell responses to the rgp160 antigen. After 2 years this response was preserved in the HAART-treated group, but not in the rgp160 immunized non-HAART group, despite comparable CD4 levels. Recall effects of the CD4-specific responses towards other antigens were seen in the rgp160-immunized HAART group. CONCLUSION: Immunization with rpg 160 leads to positive effects on HIV-specific T-cell proliferative responses in patients both with and without HAART. Immune responses after immunization is better preserved in HAART-treated patients who have low viral amounts than in individuals with high viral load and no HAART despite comparable CD4 levels during 2 years' follow-up. Interruption of HAART with return of a high viral load might thus have negative effects on T-cell functions in the long term, even if CD4 levels are kept at clinically acceptable levels.