Changes in lung function among treated HIV-positive and HIV-negative individuals: analysis of the prospective AGEhIV cohort study

Background: The AGE _hIV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGE _hIV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGE _hIV cohort accounting for smoking behaviour and other risk factors. Methods: We obtained pre-bronchodilator spirometry measurements in AGE _hIV cohort participants during biennial visits over a median of 5·9 years (IQR 5·7–6·0). Adjusted declines in forced expiratory volume in 1 s (FEV ₁), FVC, and FEV ₁/FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV ₁ and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acid-binding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582. Findings: 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (<40 copies per mL) during 1627 (95%) study visits, and 159 (32%) HIV-positive and 183 (38%) HIV-negative participants had never smoked. Adjusted declines in FEV ₁ were 10·0 mL per year faster in HIV-positive non-smokers (95% CI 4·2 to 15·7, p=0·00066) compared with HIV-negative non-smokers, and 11·1 mL per year faster in HIV-positive smokers (95% CI 0·7 to 21·4, p=0·036) compared with HIV-negative smokers. In comparison, smoking was associated with a 16·4 mL per year steeper decline in FEV ₁ among HIV-positive participants (95% CI 8·0 to 24·7, p=0·00012), and 15·3 mL per year steeper decline among HIV-negative participants (95% CI 6·7–24·0, p=0·00052) compared with not smoking. Adjusted yearly declines in FEV ₁ and FVC, but not FEV ₁/FVC, were significantly greater in HIV-positive than HIV-negative participants overall (additional decline in HIV-positive participants, FEV ₁ 10·5 mL per year [95% CI 4·7 to 16·3], p=0·00040; FVC 11·5 mL per year [2·8 to 20·3], p=0·0096; FEV ₁/FVC 0·07% per year [–0·05 to 0·19], p=0·26), with a similar observation for never-smokers (FEV ₁ 6·0 mL per year [–1·8 to 13·7], p=0·13; FVC 9·1 mL per year [–3·0 to 21·1], p=0·14; FEV ₁/FVC ratio 0·00% per year [–0·18 to −0·18], p=0·97). Higher CRP concentrations during follow-up were associated with accelerated declines in FEV ₁ and FVC among HIV-positive participants but not among HIV-negative participants. Interpretation: Treated HIV infection was associated with faster declines in both FEV ₁ and FVC, but not in the FEV ₁/FVC ratio. These changes were independent of smoking and might have been driven by ongoing interstitial or small airway damage, potentially related to increased inflammation. Funding: ZonMW, Aidsfonds, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, Merck.