Use of rosuvastatin in HIV-associated chronic obstructive pulmonary disease

Abstract

Objectives Chronic obstructive pulmonary disease (COPD) is more prevalent in HIV-infected individuals and is associated with persistent inflammation. Therapies unique to HIV are lacking. We performed a pilot study of the HMG Co-A reductase inhibitor rosuvastatin to determine effects on lung function. Design Randomized, placebo-controlled, triple-blinded trial. Methods HIV-infected individuals with abnormal lung function were recruited from an ongoing lung function study. Participants were randomized to 24 weeks of placebo (n=11) or rosuvastatin (n=11) using an adaptive randomization based on change in peripheral C-reactive protein levels at 30 days of treatment. Forced expiratory volume in one second (FEV1) and diffusing capacity for carbon monoxide (DLco) %-predicted were compared to baseline at 24 weeks in the two groups using Wilcoxon rank-sum. %-predicted change at 24 weeks in pulmonary function variables was compared between groups using simulated randomization tests. Results The placebo group experienced a significant decline in FEV1%-predicted (p=0.027), and no change in DLco%-predicted over 24 weeks. In contrast, FEV1%-predicted remained stable in the rosuvastatin group, and DLco%-predicted increased significantly (p=0.027). There was no significant difference in absolute change in either measure between placebo and rosuvastatin groups. Conclusion In a pilot study, use of rosuvastatin for 24 weeks appeared to slow worsening of airflow obstruction and to improve DLco in HIV-infected individuals with abnormal lung function, although comparison of absolute changes between the groups did not reach significance. This study is the first to test a therapy for COPD in an HIV-infected population, and large-scale clinical trials are needed.

Lung Function, Coronary Artery Disease, and Mortality in HIV

“…For example, statins are known to reduce endothelial dysfunction and CAD in HIV (51,52). In a recent pilot study, we found that statin therapy also improves lung function, including DL CO , in individuals with HIV infection and also decreases circulating endothelin-1 concentrations (53). Therefore, it is plausible that statins may be an effective multisystem therapy in HIV that can simultaneously reduce pulmonary disease and CAD by targeting the shared underlying mechanism of endothelial dysfunction.…”

Pulmonary disease in HIV-infected adults in the era of antiretroviral therapy

“…Few studies have examined lung function trajectory among persons with HIV, and decline of spirometry measures of lung function has been performed only over relatively short-term follow-up periods [54, 94, 97, 98] . Lung function normally declines with increasing age, but whether lung function declines more rapidly among persons with HIV than those without has not been proven.…”

“…HIV has been shown to be an independent risk factor for DL CO impairment in cohorts including HIV-infected and uninfected participants in both the pre- and post-ART eras [30, 66] . Interestingly, while in many cases DL CO impairment is seen in association with abnormal spirometry or radiographic emphysema [30, 66, 99, 100] (and therefore likely to represent lung disease), significant DL CO impairment is also found with normal spirometry, suggesting another pathophysiology driving gas exchange impairment in these participants [30, 48, 66, 97] (Figure 2). Certain cohorts have found diffusing impairment to correlate with abnormal echocardiogram findings, with increased tricuspid regurgitant velocity (TRV) suggesting elevated pulmonary artery pressures or cardiopulmonary dysfunction as a contributor [36, 100] , but a significant portion of HIV-infected individuals have neither COPD nor cardiac dysfunction to explain their DLco impairment.…”

Significant chronic airway abnormalities in never‐smoking HIV‐infected patients

“…It may be premature to consider treatment interventions for CHPD in PLWH. However, it is worth noting that a study in the setting of a cardiovascular screening programme, although not conclusive because it was a pilot with a small sample size, has suggested benefits of using rosuvastatin for 24 weeks to slow the worsening of airflow obstruction and improve DLCO in HIV‐infected individuals . A recent study conducted in patients with atherosclerosis from the general population also suggested that anti‐inflammatory therapy targeting the interleukin‐1β innate immunity pathway could reduce lung cancer incidence and mortality , suggesting that therapeutic interventions will be available for high‐risk patients in the near future.…”