Reduction in CD8+ cell noncytotoxic anti-HIV activity in individuals receiving highly active antiretroviral therapy during primary infection.
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.
Stranford
S A
SA
Department of Medicine, University of California, San Francisco, CA 94143; Blood Centers of the Pacific, San Francisco, CA 94118, USA.
Ong
J C
JC
Martinez-Marino
B
B
Busch
M
M
Hecht
F M
FM
Kahn
J
J
Levy
J A
JA
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003864:Depression, Chemical; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007111:Immunity, Cellular / Q000187:drug effects*; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use; D016312:Treatment Refusal; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D018119:Stavudine; D019888:Nelfinavir; D006918:Hydroxyurea