Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts

Abstract

Background: CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non-AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time.

Methods: Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years.

Results: At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term-treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group.

Conclusions: ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non-AIDS-related events by alleviating this elevation.

Keywords: CD4/CD8 ratio; CD8 T-cell count; HIV; antiretroviral therapy; primary infection.

© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Figures

Figure 1.

Flow diagram illustrating enrollment of participants with primary human immunodeficiency virus infection. ART, antiretroviral therapy.

Figure 2.

Trajectories of T-cell counts over time in early-treated primary human immunodeficiency virus (HIV) infection and chronic infection with long-term treatment. Values represent medians with interquartile ranges (IQRs); the 5th–95th percentiles of values for the control population are shaded gray. In primary HIV infection, when antiretroviral therapy (ART) was initiated within 6 months of infection, CD8 cell counts were prominently decreased at 24 months compared with the level at ART initiation (B; P = .01) and fell within the upper limit of CD8 counts for normal controls. CD4 cell counts (A; P = .002) and CD4/CD8 ratios (C; P < .001) were significantly increased compared with when treatment started. In patients with chronic infection receiving long-term treatment, CD4 cell counts (D) and CD4/CD8 ratio (F) continued to increase over the 8 years with sustained viral suppression. However, CD8 counts (E) remained stable over time and were higher than those in the early ART group at 24 months of treatment.

Figure 3.

Trajectories of CD4 (A) and CD8 (B) T-cell counts and CD4/CD8 ratios (C) over time in primary human immunodeficiency virus (HIV) infection. Dashed arrows show the median time of antiretroviral therapy (ART) initiation in the early ART (eART) (red) or delayed ART (dART) (blue) group. The 5th–95th percentiles of values in the control population are shaded gray. A, CD4 cell counts in the eART group were higher than in the dART (P = .048) or no-ART (nART) (P = .01) group at 24 months. B, CD8 cell counts in the nART group remained stable; at 24 months, CD8 counts in the eART group were lower than in the nART group (P = .004) though still elevated compared with the control group (P < .001). C, CD4/CD8 ratios in the nART group declined over time; those in the eART group were higher than in the nART group (P < .001) at 24 months.