Reduction in CD8+ cell noncytotoxic anti-HIV activity in individuals receiving highly active antiretroviral therapy during primary infection

Abstract

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.

Figure 1

Effect of HAART treatment on CD8⁺ cell noncytotoxic anti-HIV activity in primary infection. The percentage of suppression of HIV-1_SF33 replication at a CD8⁺:CD4⁺ cell ratio of 0.5:1 is presented for 21 individuals experiencing the primary stages of HIV infection and receiving highly active antiretroviral therapy for a period of 24 weeks. Week 0 represents the level of CD8⁺ cell suppression before the initiation of HAART, compared with weeks 4, 12, or 24 of treatment. Statistical significance was determined by comparing the actual suppression values of all participants at week 0 with these same measurements at week 24 (P = 0.01). Red line, maintained or enhanced antiviral response; blue line, decreased antiviral response.

Figure 2

CD8⁺ cell noncytotoxic anti-HIV activity in untreated primary infection subjects. The percentage of suppression of HIV-1_SF33 replication at a CD8⁺:CD4⁺ cell ratio of 0.5:1 is presented for five individuals experiencing the primary stages of HIV infection and receiving no therapeutic intervention. Week 0 represents the level of CD8⁺ cell suppression at the time each patient elected not to receive treatment, compared with weeks 4, 12, and 24 of follow-up. No statistical significance was observed when comparing the actual suppression values of all participants at week 0 with these same measurements at week 24 (P = 0.1).