Objectives:

To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals.

Design:

A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV-positive males aged 45 years or less and age-matched and elderly (≥ 65 years) HIV-uninfected individuals.

Methods:

Age-related changes to monocyte phenotype and function were measured in whole blood assays ex vivo on both CD14++ CD16−(CD14+) and CD14 variable CD16+(CD16+) subsets. Plasma markers relevant to innate immune activation were measured by ELISA.

Results:

Monocytes from young viremic HIV-positive males resemble those from elderly controls, and show increased expression of CD11b (P< 0.0001 on CD14+ and CD16+ subsets) and decreased expression of CD62L and CD115 (P= 0.04 and 0.001, respectively, on CD14+ monocytes) when compared with young uninfected controls. These changes were also present in young virologically suppressed HIV-positive males. Innate immune activation markers neopterin, soluble CD163 and CXCL10 were elevated in both young viremic (P< 0.0001 for all) and virologically suppressed (P= 0.0005, 0.003 and 0.002, respectively) HIV-positive males with levels in suppressed individuals resembling those observed in elderly controls. Like the elderly, CD14+ monocytes from young HIV-positive males exhibited impaired phagocytic function (P= 0.007) and telomere-shortening (P= 0.03) as compared with young uninfected controls.

Conclusion:

HIV infection induces changes to monocyte phenotype and function in young HIV-positive males that mimic those observed in elderly uninfected individuals, suggesting HIV may accelerate age-related changes to monocytes. Importantly, these defects persist in virologically suppressed HIV-positive individuals.