Pathogenesis of HIV and the Lung

Abstract

Antiretroviral therapy has improved longevity for HIV-infected persons, but long-term HIV infection is now complicated by increased rates of chronic medical conditions including pulmonary disorders. Chronic obstructive pulmonary disease, lung cancer, asthma, and pulmonary hypertension are becoming common comorbidities of HIV infection, and these diseases may develop as a result of HIV-related risk factors such as antiretroviral drug toxicities, colonization by infectious organisms, HIV viremia, immune activation, or immune dysfunction. It also appears that the ability to control HIV infection does not completely eliminate the risk for infectious complications such as bacterial pneumonia and tuberculosis. The effect of HIV infection on lung-specific immune responses is being elucidated to help develop better prevention and treatment strategies in HIV-infected persons.

Impact of HIV infection and smoking on lung immunity and related disorders

“…Much has been written about the occurrence of lung cancer in HIV-infected patients, with initial studies variously documenting it to be increased, decreased or the same in HIV-infected patients, compared to the general population [133][134][135][136][137][138][139][140][141]. More recently, several studies have suggested that there is indeed an increased incidence of lung cancer in HIV-infected patients, especially evident in the post-HAART era and associated with a poor outcome [134-138, 140, 141], with the adjusted risk ranging from 2.0 to 7.0 [18].…”

“…oncogenic role of HIV and chronic immunosuppression) and increased susceptibility of HIV-infected persons to mutagens/carcinogens such as chronic inflammation-derived ROS and possibly antiretroviral agents [135,141]. However, the role of immunosuppression is unclear, with several studies suggesting involvement [136,139], while others have presented evidence to the contrary [138].…”

“…Recent research has also focused on the role of P. jirovecii colonisation in the pathogenesis and progression of COPD [141,142,152]. Although there is clearly an increased rate of colonisation with this pathogen in patients with COPD [142], the link may be purely an epiphenomenon related to structural lung damage and/or immunosuppression due to corticosteroid use.…”

“…Despite a number of reviews on the topic [141,146,153,154], it remains difficult to determine whether COPD in the setting of HIV infection occurs as a consequence of higher rates of smoking, drug abuse, pulmonary infections or other risk factors, including occupational or environmental exposures, and low socioeconomic status [153]. These reviews have also focused on potential mechanisms that may be involved in HIV-associated COPD, such as high-risk behaviour (including cigarette smoking), increased susceptibility to pulmonary infection and colonisation, aberrant inflammatory responses, altered oxidant/ antioxidant defences, increased apoptosis and effects of HAART [141,146,154].…”

“…These reviews have also focused on potential mechanisms that may be involved in HIV-associated COPD, such as high-risk behaviour (including cigarette smoking), increased susceptibility to pulmonary infection and colonisation, aberrant inflammatory responses, altered oxidant/ antioxidant defences, increased apoptosis and effects of HAART [141,146,154]. Irrespective of the mechanisms involved in HIV-associated COPD, cessation of smoking as a preventive strategy is certainly a priority, while the role of early implementation of HAART remains to be established in this setting.…”