Lung CD4(+) depletion/dysfunction, CD8(+) alveolitis, smoking, and poor HIV control are features of HIV-associated COPD, but these changes have not been evaluated in smokers at-risk for COPD. We evaluated the impact of viral suppression following initiation of antiretroviral therapy (ART) on HIV-specific immunity and lung CD4:CD8 balance.
Using flow cytometry, we assessed lung/blood T-cell immunity in 12 actively- smoking HIV+ patients pre- and post-ART following viral suppression.
HIV suppression resulted in enhanced lung/systemic HIV-specific CD4(+) immunity without significant changes in CD8(+) responses. We observed an increase in lung CD4:CD8 ratios and CD4(+) frequencies, decreased CD8(+) numbers, and resolution of CD8(+) alveolitis post -: ART, in 9/12 individuals. Viral suppression reduced Fas-receptor and programmed death-1 expression in lung CD4(+) T-cells, correlating with enhanced effector function and reduced susceptibility to apoptosis. HIV suppression rescued peripheral, but not lung, CD4(+) HIV-specific proliferation resulting in augmented effector multifunction.
Together, our results demonstrate that HIV suppression restores lung mucosal HIV-specific CD4(+) T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8(+) alveolitis in active smokers. Peripheral expansion and redistribution of CD4(+) T-cells, and increased resistance to apoptosis are two mechanisms contributing to immunologic improvement following viral suppression in patients at risk for HIV-associated COPD.