People with HIV have impaired respiratory health, even when viral load is undetectable

HIV-positive people have impaired respiratory health, even when they have viral suppression with antiretroviral therapy (ART), investigators from London report in HIV Medicine. Respiratory health was compared between HIV-positive and HIV-negative outpatients. Individuals with HIV had poorer respiratory health and were more likely to report breathlessness than HIV-negative participants, findings which remained unchanged when analysis focused on ART-treated HIV-positive people with an undetectable viral load.

“To our knowledge, no other study has used patient-reported outcomes to compare respiratory health status in HIV-positive and HIV-negative populations,” comment the authors. “Our results suggest that HIV remains associated with impaired respiratory health despite virological suppression with ART.”

Thanks to ART, many HIV-positive people now have a near-normal life expectancy. However, rates of heart, liver and kidney disease remain elevated. Research involving US military veterans also found that HIV-positive people had a significantly higher prevalence of chronic obstructive pulmonary disease (COPD).

Investigators at the Royal Free Hospital, London, wanted to further understand the relationship between HIV infection and respiratory health in the modern ART era.

They therefore designed a study involving 197 HIV-positive people and 93 HIV-negative controls attending their hospital’s HIV and sexual health outpatient clinics in 2015. Participants completed a questionnaire focusing on their respiratory health (St George’s Respiratory Questionnaire – SGRQ) and a separate Medical Research Council (MRC) questionnaire on breathlessness. Participants also had a spirometry test to assess lung function.

The median CD4 cell count of the HIV-positive participants was 627 cells/mm³. Most (94%) reported taking ART, with a median duration of therapy of seven years. Overall, 89% of people had an undetectable viral load (below 40 copies/ml), including 93% of individuals taking ART.

There were no differences in gender, educational attainment, or country of birth between the HIV-positive and HIV-negative participants. However, people with HIV were more likely to be white compared to the HIV-negative controls (72% vs 60%) and the HIV-negative people had a younger median age than the HIV-positive people (43 vs 50 years).

Both groups had similar prevalences of co-morbidities such as asthma, COPD, heart disease and stroke. However, depression was more common in people with HIV (20% vs 14%).

Equal proportions of both groups reported being current (30% vs 33%) or ex- (28% vs 25%) smokers, although people with HIV smoked more cigarettes per day (15 vs 10, p<0.001). Similar proportions of HIV-positive and HIV-negative participants reported current recreational drug use (30% vs 20%), though people with HIV were more likely to report historic drug use (61% vs 48%).

Lung function measured by spirometry was within normal limits for most people, but 11% of HIV-positive people and 9% of HIV-negative individuals had evidence of airflow obstruction.

There was a higher prevalence of respiratory health impairment measured by SGRQ (p < 0.001) and breathlessness among the people with HIV (p = 0.001) compared to HIV-negative participants.

“Breathlessness was common in HIV-positive participants, with 47%...reporting this to be present and of at least moderate severity, compared with 25% of the HIV-negative participants,” write the authors. “Using the SGRQ respiratory health questionnaire…we found a 6-point difference in the median total score between HIV-positive and HIV-negative groups.”

Impaired respiratory health was associated with poorer lung function and depression. Combining the HIV-positive and HIV-negative groups, there were no significant associations between respiratory health and gender, ethnicity, smoking status and drug use. An association with higher BMI was of borderline significance.

In an analysis restricted to HIV-positive individuals, neither current nor nadir CD4 count was significantly associated with SGRQ score. No significant difference in respiratory health score was identified according to viral load. However, there was some evidence that people with longer-standing HIV infection had poorer SGRQ scores. There was also a relationship between poorer respiratory health and longer interval between diagnosis with HIV and starting ART.

After adjustment for potential confounders, HIV infection was independently associated with an increased SGRQ score (adjusted fold-change, 1.54; 95% CI, 1.14-2.09, p = 0.005) and higher chances of at least moderate breathlessness (aOR = 2.84; 95% CI, 1.35-6.00, p = 0.006).

These findings remained unchanged when comparing HIV-positive people with an undetectable viral load with the HIV-negative participants.

Other significant risk factors for breathlessness were female gender (p = 0.001) and depression (p < 0.001).

The authors offer several possible explanations for their findings:

• Lung disease before starting ART.
• Cardiovascular disease and other non-lung-related co-morbidities that cause respiratory symptoms.
• Depression.
• Persistent immune dysregulation despite virologically suppressive ART leading to hardening of the arteries.

“Interventions that can preserve the respiratory health of people with chronic HIV infection are needed,” conclude the authors. “However, why HIV infection is associated with apparent worse respiratory health even in never-smokers remains uncertain and requires further investigation.”