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Immune activation in HIV-1 patients experiencing transiently detectable viremia during antiretroviral treatment
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle WA
Babafemi Taiwo1, Peter Hunt2, Rajesh Gandhi3, Andrew Ellingson4, Matthew McKenna4, Jeffrey Jacobson5 , Barbara Gripshover6, and Ronald Bosch4
1Northwestern University, Chicago, IL; 2University of California, San Francisco; 3Harvard Medical School, Boston, MA; 4Harvard Sch. of Public Health, Boston, 5Drexel University College of Medicine, Philadelphia, PA; 6Case Western Reserve University, Cleveland, Ohio
CONCLUSIONS
Viral blips during suppressive ART are not associated with increased CD8+ T cell activation, suggesting that transient low-level viremia is unlikely to worsen heightened level of CD8+ T cell activation.
Higher CD8+ T cell activation during virologically suppressive (VL < 50 copies/ml) ART is associated with development of a subsequent viral
blip, but the effect appears to be of limited magnitude.
UPDATED ABSTRACT
Background: Transiently detectable viremia (viral blip) is common during otherwise suppressive antiretroviral therapy (ART), but the immunologic predictors and consequences are incompletely characterized. We examined whether viral blips are associated with increases in immune activation and whether the level of immune activation during viral suppression is predictive of subsequent viral blip.
Methods: An observational study was conducted on patients with CD8+ T cell activation (% CD38+/HLA-DR+) data in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) and ALLRT parent protocols. CD8+ T cell activation was determined from fresh blood specimens. Viral blip was defined as isolated increases in plasma HIV-1 RNA (vRNA) to levels between 50 and 400 c/mL during ART followed by resuppression to <50 copies/mL. CD8+ T cell activation at the viral blip timepoint was compared to levels at the prior and subsequent vRNA <50 c/mL (Roche Amplicor) timepoints using generalized estimating equations regression models. Separately, using a matched case- control design and analysis by conditional logistic regression, CD8+ T cell activation at a vRNA<50 c/mL timepoint was compared between subjects who subsequently experienced viral blips (cases) and those who maintained vRNA<50 c/mL (controls), matched by parent study, sex, age (±5 years), duration of vRNA suppression (±6 months) and duration of ART (±6 months).
Results: Among 116 subjects with viral blips and concurrently measured immune activation (85% male; median HIV RNA at blip 93 c/mL; median CD4 count prior to blip=489 cells/mm3; median CD8+ T cell activation prior to blip=23%), viral blips were not significantly associated with changes in CD8+ T cell activation
(95% CI: -0.5, 2.2 percentage-points; p=0.21). Separate analyses examined CD8+ T cell activation at the time of viral suppression (<50 c/mL) in 123 subjects with subsequent viral blips (89% male; median CD4 count=547 cells/mm3; median CD8 activation=20%) and 629 matched controls. CD8+ T cell activation was significantly associated with subsequent development of a viral blip (odds ratio=1.19 per 10 percentage points higher CD8+ T cell activation; 95% CI: 1.01, 1.41; p=0.034).
Conclusions: Viral blips during suppressive ART are not associated with increased CD8 cell activation. This finding suggests that transient low-level viremia is unlikely to worsen the heightened level of CD8 cell activation found in HIV+ patients on suppressive ART. Higher CD8+ T cell activation during viral suppression is associated with a subsequent viral blip.
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