ABSTRACT
Early treatment intervention during human immunodeficiency virus (HIV) infection is a strategy aimed to preserve and/or enhance the developing anti-HIV immune responses. We report the effect of highly active antiretroviral therapy (HAART) combined with intermittent subcutaneous doses of Interleukin 2 (IL-2) on CD8(+) cell noncytotoxic anti-HIV responses (CNAR), as well as on viral loads and CD4(+) cell/CD8(+) cell numbers in subjects with primary HIV-1 infection. Twenty-four patients received HAART, 24 received a combination of HAART plus IL-2, and 12 elected no-therapy. In comparison to HAART alone, IL-2 treatment led to significant increases in CD4(+) cell numbers through week 48 of the study. No effect was observed on viral loads or the CD8(+) cell population. The first cycle of IL-2 enhanced CNAR; later cycles showed no substantial effect. This study suggests that HAART combined with IL-2 could provide an immunologic benefit in the treatment of early HIV infection.
Subject(s)
Anti-HIV Agents/therapeutic use , CD8-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV-1/drug effects , Interleukin-2/therapeutic use , Adult , Aged , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/immunology , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV-1/immunology , Humans , Interleukin-2/administration & dosage , Male , Middle Aged , RNA, Viral/blood , Viral LoadABSTRACT
Recent advances in the ability to detect people at the early stages of HIV infection now permit the initiation of antiretroviral treatment before the full complement of antiviral immune responses has evolved. However, the influence of early treatment interventions on the developing anti-HIV immune response is unknown. This study investigates the impact of standard highly active antiretroviral therapy (HAART) during the primary stages of HIV infection on the plasma HIV-1 RNA level, CD4(+) and CD8(+) lymphocyte counts, and the CD8(+) cell anti-HIV response. Individuals treated with HAART within 6 months of infection showed dramatic and rapid reductions in HIV-1 RNA levels along with modest increases in CD4(+) cell number and decreases in CD8(+) cell numbers. A significant reduction in the level of CD8(+) cell noncytotoxic suppression of HIV replication was observed over time in most participants receiving HAART. Importantly, those individuals choosing not to receive therapy maintained low but detectable HIV-1 RNA levels and showed no reduction in their CD8(+) cell antiviral response. These results suggest that either continued antigenic challenge is required to sustain CD8(+) cell-mediated anti-HIV activity, or that HAART has some inhibitory effect on this important immunologic function during the early stages of infection.
