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HIV & Aging Clinical Recommendations
According to the Global Initiative for Chronic Obstructive Lung Diseases, COPD is “characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposures to noxious particles or gases” (GSDMP-COPD 2017). The major risk factor for COPD is cigarette smoking, but occupational and environmental exposures also contribute. Prior bacterial pneumonia and Pneumocystis pneumonia are associated with airflow obstruction on pulmonary function testing (Morris 2000), and given their increased incidence in those with HIV, may play an important role in the risk and progression of COPD in HIV-positive persons.
COPD can occur at any CD4 cell count or HIV viral load in HIV-positive persons. However, the risk of COPD was increased in HIV-positive persons with a high viral load (>200,000 copies/ml) after adjusting for antiretroviral therapy (ART) use (Drummond 2012). COPD may progress more rapidly in HIV-positive persons with poorly controlled HIV. Amongst HIV-positive injection drug users, the rate of decline in the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) was accelerated in patients with high HIV viral load (defined as >75,000 copies/ml) and with low CD4 cell count (defined as <100 cells/µl), when compared to patients with better controlled HIV disease and to those without HIV infection (Drummond 2013).
The diagnosis of COPD should be suspected in patients who have chronic cough or sputum production, dyspnea, and/or exposure to risk factors for the disease (GSDMP-COPD 2017). The diagnosis of COPD requires spirometry, preferably with bronchodilator testing to demonstrate persistent airflow limitation; the definition of persistent airflow limitation requires that the ratio of the forced expiratory volume in one second (FEV1) to the forced vital capacity (FVC) be less than 70%; alternatively, an FEV1/FVC that is less than 95% of the lower limit of normal, in association with an FEV1 of less than 80% of predicted can also be used (GSDMP-COPD 2017). Among older patients, using a threshold of the FEV1/FVC of less than 95% of the lower limit of normal results in fewer false-positive diagnoses of COPD (Hankinson 1999). Screening spirometry to detect COPD in asymptomatic populations is generally not recommended (Lin 2008), although studies have not addressed whether screening is beneficial in PLWH. A preliminary study conducted in one center found that HIV-positive outpatients had a high prevalence of symptoms and exposures consistent with COPD, and approximately one quarter of those who completed screening spirometry were diagnosed with COPD (Lambert 2016).
In HIV-positive patients with chronic respiratory symptoms, health care providers should obtain spirometry. Complete pulmonary function testing including measurement of diffusing capacity should also be considered, as PLWH s are more likely to have a decrease in diffusing capacity despite relatively normal spirometry (Gingo 2010). Indeed, HIV-positive persons have an increased risk of a moderately to severely impaired diffusing capacity, defined as <60% predicted normal, compared to uninfected persons after adjusting for smoking and other risk factors (Crothers 2013; Fitzpatrick 2013). A decreased diffusing capacity suggests the presence of emphysema or other disease processes such as pulmonary arterial hypertension or pulmonary fibrosis that interfere with normal gas exchange within the lung.
In the absence of data on the treatment of COPD specifically in the setting of HIV infection, current therapy of COPD in PLWH should follow the management guidelines proposed for the general population (GSDMP-COPD 2017). In the Global Obstructive Lung Disease (GOLD) 2017 guidelines, therapy for COPD is driven by symptoms and history of exacerbations rather than by severity of airflow limitation, which is reflected by the FEV1 % predicted (GSDMP-COPD 2017). Symptoms should be assessed using the COPD Assessment Test (CAT) or the Medical Research Council (MRC) Dyspnea score. In general, therapy is initiated for symptomatic COPD patients with inhaled bronchodilators. For patients who have regular symptoms, monotherapy with a long acting inhaled beta-agonist (LABA) or antimuscarinic (LAMA) is recommended; combination therapy with a LABA plus LAMA should be prescribed if symptoms are persistent (GSDMP-COPD 2017). Inhaled steroids are generally reserved for patients who have exacerbations (GSDMP-COPD 2017). HIV-positive persons may have a greater risk of COPD exacerbation compared to HIV-negative persons, although whether and how to tailor therapy for HIV-positive patients with frequent exacerbations remains uncertain (Depp 2016; Lambert 2015). Thus, roflumilast or azithromycin may be considered for HIV-positive patients who continue to have exacerbations despite use of triple inhaled therapy (LABA, LAMA, ICS) as per COPD guidelines (GSDMP-COPD 2017).
Special consideration should be given to a few key aspects of COPD management for PLWH. As with HIV-negative patients, smoking cessation should be prioritized. Phaseolus also be monitored for potential complications and interactions between COPD medications and antiretroviral therapy. Protease inhibitors, particularly ritonavir, can increase systemic levels of inhaled or intranasal fluticasone. Cushing’s syndrome or adrenal suppression may result when corticosteroids are tapered (Soldatos 2005; St Germain 2007). The use of high-dose inhaled corticosteroids also requires careful monitoring, as inhaled corticosteroids are associated with increased risk of oral candidiasis, bacterial pneumonia (Calverley 2007; Drummond 2008), and tuberculosis (Brassard 2011). The regular use of systemic steroids should preferably be avoided. Given the potential complications associated with steroids, additional studies on the efficacy and/or effectiveness and safety of these medications in HIV-positive persons with COPD are needed.
In addition, COPD is associated with several comorbidities that may particularly complicate care of elderly patients. These include cardiovascular disease, muscle wasting, osteoporosis, malnutrition, depression, anxiety and lung cancer (Nazir 2009). Providers should review vaccination records with their HIV-positive patients to ensure that all patients have received the recommended pneumococcal (both PCV13 and PPSV23) (CDC 2012; Kim 2017) and yearly inactivated influenza vaccine.
PLWH with COPD should be considered for participation in pulmonary rehabilitation programs. Lung disease may be an important determinant contributing to poor physical function in HIV-positive persons. Among HIV-positive Veterans, chronic obstructive lung disease (COPD and/or asthma) was among the top comorbid conditions independently associated with self-reported increased physical disability (Oursler 2006). Airflow limitation, as reflected by a low FEV1 is also associated with decreased 6-minute walk distance in PLWH (GSDMP-COPD 2017; Campo 2014). Emphysema, even when only mild, has also been associated with a greater decrease in 6 minute walk distance in HIV-infected compared to uninfected individuals (Campo 2014). Reasons why HIV appears to result in greater physical limitation in COPD patients are not well understood, but could be related to concomitant comorbidities, muscle loss, and inflammation associated with HIV.
In studies of HIV-positive persons with COPD, physical functioning is significantly improved with participation in pulmonary rehabilitation programs (Nici 2006). In general, pulmonary rehabilitation programs should be prescribed in persons with COPD who are symptomatic, have frequent exacerbations, or who have more severe disease (e.g. an FEV1 <50% predicted (GSDMP-COPD 2017). Studies support the safety and potential benefit of exercise training in PLWH (O’Brien 2010) although further studies are needed to determine the role and optimal type of exercise training in HIV-positive patients, particularly older patients with concomitant comorbid diseases such as COPD.
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017.
Lambert AA, Kirk GD, Astemborski J, Mehta SH, Wise RA, Drummond MB. HIV Infection Is Associated With Increased Risk for Acute Exacerbation of COPD. J Acquir Immune Defic Syndr 2015; 69(1):68-74.