Abstract
BACKGROUND: Among patients with human immunodeficiency virus (HIV), pulmonary complications are a common cause of morbidity and mortality. Emerging evidence suggests that respiratory viruses contribute to this disease burden. Although HIV is known to alter other mucosal surfaces including the GI tract and vagina, its effect on the upper respiratory mucosa, the primary target of respiratory viruses, has not been well described. We sought to characterize the effect of HIV on the upper respiratory mucosal immune environment. METHODS: Ten HIV-infected patients and 10 sex-matched uninfected controls were enrolled. Subjects were ages 18–49, nonsmokers, and otherwise healthy. HIV-infected subjects had complete viral load suppression for at least 6 months prior to participation. Subjects provided serum samples and underwent nasal mucosal sampling procedures—epithelial lining fluid (ELF) collection, nasal lavage (NLF) and nasal biopsy. Serum, ELF, and NLF were analyzed using ELISAs targeted at pro-inflammatory cytokines. NLF was analyzed by flow cytometry for nasal-specific immune cells. RESULTS: T-cells in NLF, including both CD8 and CD4 populations, were significantly decreased in HIV-infected compared with uninfected subjects. We also found decreased numbers of neutrophils. Additionally, we identified diminished levels of IL-16 in ELF, a T-cell chemoattractant in HIV-infected subjects; however, all other cytokines and chemokines were similar between the two groups. These findings were in contrast to an earlier study we had done in six HIV-infected men with variable levels of HIV control and age-matched control subjects which also demonstrated decreased levels of other pro-inflammatory cytokines, including IL-Iβ, IL-8, and IL-5 in those with HIV. CONCLUSION: The mechanism underlying the morbidity and mortality of respiratory viruses in HIV-infected patients is unclear. However, we identified that HIV infection does result in relative upper respiratory immune suppression, including in both CD4 and CD8 T-cell populations, despite otherwise excellent systemic control of HIV. We hypothesize that this suppression persists in viral infection leading to an impaired immune response and prolonged respiratory virus replication, contributing to the observed burden of disease in this population. DISCLOSURES: All authors: No reported disclosures.