Effective HIV Suppression Restores Lung Mucosal CD4+ Viral Immunity

Viral suppression is key in restoring mucosal CD4+ viral immunity and resolving CD8+ alveolitis in patients with HIV, actively smoking and at risk for developing COPD.

Successful viral suppression can restore lung mucosal human immunodeficiency virus (HIV)-specific CD4+ T-cell immunity and correct CD8+ alveolitis in patients living with HIV, who actively smoke, restoring the CD4:CD8 balance, according to a study published online in the Journal of Infectious Diseases.1

Iulia Popescu, PhD, of the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh School of Medicine in Pennsylvania and colleagues used flow cytometry to measure T-cell mediated immunity in patients who were both active smokers and HIV-infected (n=12) before and after antiretroviral therapy (ART). Patients were recruited from the Johns Hopkins HIV Care Clinic, who had bronchoscopy results before and after receiving ART available for data analysis. In addition, patients had no history of taking antibiotics or steroids for respiratory disease or had been previously diagnosed with pneumonia within 6 weeks of study enrollment.

Following ART, 9 out of 12 patients experienced increased ratios of CD4:CD8 and CD4+ frequencies, a reduction in CD8+ numbers, and clearing of CD8+ alveolitis.

Researchers said that “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 chronic obstructive pulmonary disease (COPD).”

HIV-associated COPD features include CD4+ depletion and dysfunction in the lungs and CD8+ alveolitis. Smoking and poor viral suppression are contributing factors. This is the first time researchers have assessed these changes in active smokers with HIV who are at increased risk for developing COPD.

“Viral suppression reduced Fas-receptor [also known as apoptosis antigen 1] and programmed death-1 expression in lung CD4+ T-cells…HIV suppression rescued peripheral, but not lung, CD4+ HIV-specific proliferation CD4+ HIV-specific proliferation resulting in augmented effector multifunction,” Dr Popescu and colleagues reported.

Researchers noted several limitations to their study. First, they acknowledged the small size of the sample and said that clinical relevance of the results is not yet clear because results could be due to improved viremia control.

Dr Popescu and colleagues also said they were unable to distinguish inflammation caused by smoking because all patients were active smokers during the study. They added that more studies are needed to examine smoking’s pro-inflammatory effects.

Despite these limitations, researchers said that the immunologic results show how essential viral suppression is in patients with HIV who are at risk for HIV-associated COPD. Information illustrated by the study “strongly support[s] that initiation of ART restores the lung and mucosal environment to a more physiologic CD4:CD8 balance despite ongoing smoking in patients.”

Researchers concluded the study by saying that better understanding of “underlying pulmonary immune mechanisms in patients at risk for developing HIV-associated COPD, may lead to a more comprehensive strategy and uncover novel targets to prevent this important complication of chronic HIV-infection.”

The study was funded by the National Institutes of Health, and researchers reported no conflicts of interest.

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  1. Popescu I, Drummond MB, Gama L, et al. HIV suppression restores lung mucosal CD4+ T-Cell viral immunity and resolves CD8+ alveolitis in patients at risk for HIV-associated COPDJ Infect Dis. 2016; doi:10.1093/infdis/jiw422.