Paper # 517|
ART Initiation during Acute/Early HIV Infection Compared to Later ART Initiation Is Associated with Improved Immunologic and Virologic Parameters during Suppressive ART
Vivek Jain*1,2, W Hartogensis1,2, P Bacchetti2, P Hunt1,2, L Epling1,2, E Sinclair1,2, T-H Lee3, M Busch3, F Hecht1,2, and S Deeks1,2
1San Francisco Gen Hosp, CA, US; 2Univ of California, San Francisco, US; and 3Blood Systems Res Inst, San Francisco, CA, US
Background: CD4+ and CD8+ T
cell activation levels often remain elevated in individuals on ART initiated
during chronic infection. This persistent inflammatory state has been
associated with blunted CD4+ T cell recovery and early mortality
during suppressive ART. The relationship of timing of ART initiation with
on-ART levels of inflammation and with the size of the persistent viral
reservoir is incompletely understood.
Methods: Individuals with acute/early HIV infection
(<6 months) who started ART early (<6 months after estimated date of HIV
infection) vs later (≥2 years) and who maintained ≥2 years of
subsequent virologic suppression were identified in the UCSF Options Project.
We assessed T cell activation by mulitparameter flow cytometry to detect expression
of CD38, HLA-DR, CCR5, PD-1, CD45RA, and CCR7 on CD8+ and CD4+
T cells. We compared T cell activation during ART between early and later
treated groups. At-risk uninfected persons served as additional controls.
Results: In unadjusted analyses, the later ART group
had a higher frequency of activated CD8+ T cells on-ART (n = 32,
mean 28.8%) compared to the early ART group (n = 34, mean 22.1%, p = 0.009).
Similarly, later ART had a higher frequency of activated CD4+ T
cells than early ART (7.5% vs 5.2%, p = 0.06). Although early ART
participants had better on-ART CD8+ T cell activation levels, these
levels remained elevated compared to HIV– controls (p = 0.02
and 0.01 for early ART vs HIV–, and late ART vs HIV–,
respectively). The persistent T cell activation associated with deferred ART
was observed in central memory T cell subsets. Deferred therapy was associated
with a 4.8-fold higher level of proviral DNA (p = 0.0045) and 3.2 S/Co
units higher cell-associated RNA (p = 0.035). The size of the reservoir
during ART was associated with the % activated (CD38, HLA-DR, CCR5, PD1) CD4+
and CD8+ T cells.
Conclusions: In recently HIV-infected individuals,
delaying ART was associated with higher CD4+ and CD8+ T
cell activation levels and larger HIV cellular reservoirs during virologic
suppression. This may be partially mediated by the extent of CD4+ T
cell depletion and/or cumulative exposure to viremia prior to ART initiation.
These results, while observational, suggest that ART initiation in the first 6
months of infection may be associated with lower on-therapy T cell activation
levels and smaller HIV reservoirs compared with later ART initiation.