RESUMO
BACKGROUND: HIV is associated with accelerated decline in lung function and increased risk for chronic obstructive pulmonary disease (COPD). Recently, there has been growing attention toward the impairment in the diffusing capacity of the lungs for carbon monoxide (DLCO), a marker of pulmonary gas exchange, observed among persons living with HIV. Although increased emphysema can contribute to the DLCO impairment observed, other factors may drive this association. METHODS: Using cross-sectional data from the Study of HIV in the Etiology of Lung Disease, we studied the association between HIV and DLCO independent of emphysema. We also analyzed the joint influence of HIV and COPD on DLCO impairment. An analysis was conducted among 339 participants (229 with HIV) with lung function and chest CT imaging data. Multivariable regression models were generated with percent predicted DLCO and odds of DLCO impairment as outcomes. RESULTS: After adjusting for confounders, including emphysema severity, HIV was associated with lower DLCO (ß -4.02%; P = 0.020) and higher odds of DLCO impairment (odds ratio 1.93; P = 0.017). Even among those without COPD, HIV was independently associated with lower DLCO (ß -3.89%; P = 0.049). Compared with HIV-uninfected participants without COPD, those with both HIV and COPD experienced the greatest impairment in DLCO (ß -14.81; P < 0.001). CONCLUSIONS: HIV is associated with impaired pulmonary gas exchange independent of emphysema severity. Our data also suggest a potentially additive influence between HIV and COPD on DLCO impairment. Further studies should investigate the other factors, including pulmonary vascular disease, which may contribute to DLCO impairment among persons living with HIV.
Assuntos
Enfisema , Infecções por HIV , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Monóxido de Carbono , Estudos Transversais , Enfisema/complicações , Infecções por HIV/complicações , Humanos , Pulmão , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/complicaçõesRESUMO
People living with HIV (PLWH) have a higher prevalence of respiratory symptoms than people without human immunodeficiency virus (HIV). Antiretroviral therapy has been associated with worsened airflow limitation. This cross-sectional study assessed respiratory health impairment among PLWH and its association with protease inhibitor use using data from Multicenter AIDS Cohort Study visits between April 1, 2017 and March 31, 2018. Participants completed the St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea scale, spirometry, and diffusion capacity measurement. Visit data were compared among PI users, non-PI users, and men without HIV. Binary and ordinal logistic models were used to determine the associations between HIV status, PI use, and covariates with primary outcomes of dichotomized SGRQ and mMRC dyspnea scores. Of PI users, 57/177 (32.2%) self-reported pulmonary disease compared with 132/501 (26.4%) of non-PI users and 105/547 (19.2%) men without HIV. Of PI users, 77/177 (45.3%) had SGRQ scores ≥10, while 171/501 (34.7%) of non-PI users and 162/549 (29.9%) of people living without HIV had SGRQ scores ≥10 (p = .001). Adjusted models found an association between PI use and SGRQ score ≥10 [odds ratio (OR) 1.91 (95% confidence interval [CI] 1.29-2.82), ref: HIV negative and OR 1.50 (95% CI 1.01-2.22) ref: non-PI users]. A similar association was found with mMRC scores and PI use [OR 1.79 (95% CI 1.21-2.64), ref: HIV negative and OR 1.53 (95% CI 1.04-2.25), ref: non-PI users]. PI use is associated with worse respiratory health status, increased dyspnea, and an increased prevalence of self-reported pulmonary disease.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Doença Pulmonar Obstrutiva Crônica , Estudos de Coortes , Estudos Transversais , Dispneia/diagnóstico , Dispneia/epidemiologia , Volume Expiratório Forçado , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Inibidores de Proteases , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Chronic respiratory disease represents an important comorbidity for persons living with HIV (PLWH). HIV itself is associated with greater impairment in lung function. We aimed to determine the association between declining lung function and both quality of life (QOL) and health care utilization for PLWH. METHODS: Using longitudinal data from the Study of HIV Infection in the Etiology of Lung Disease 2009-2017, we studied the association between changes in lung function and both QOL and acute care events (emergency department visit or hospitalization). The Medical Outcomes Studies-HIV Questionnaire provided QOL domains. Multivariable regression models were performed with generalized estimating equations accounting for 1499 participants, 485 with HIV, contributing 10,825 spirometry visits. RESULTS: Among PLWH, decreased FEV1 was associated with worse physical health for those with higher viral load [ß: -1.66, 95% confidence interval (CI): -3.11 to -0.39] compared to those with viral suppression (ß: -0.58, 95% CI: -1.06 to -0.162), even in those without airflow obstruction. Lower FEV1 was also associated with increased odds of both emergency department (odds ratio: 1.21, 95% CI: 1.09 to 1.34) and inpatient (odds ratio: 1.26, 95% CI: 1.12 to 1.42) hospitalizations for PLWH. Lung function was not associated with increased odds of acute care events for HIV-uninfected participants. CONCLUSIONS: FEV1 declines represent an independent predictor of QOL and acute care events among PLWH. Although the generalizability of these results may be limited, because of the high-risk population included, findings suggest that care for PLWH should involve monitoring FEV1 over time, especially in those with poor virologic control, with emphasis on the development and implementation of interventions to mitigate lung function decline.
Assuntos
Infecções por HIV/complicações , Pneumopatias/complicações , Pulmão/fisiopatologia , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida , Estudos de Coortes , Testes Diagnósticos de Rotina , Feminino , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espirometria , Carga ViralRESUMO
We report that a major subpopulation of monocyte-derived macrophages (MDMs) contains high levels of dUTP, which is incorporated into HIV-1 DNA during reverse transcription (U/A pairs), resulting in pre-integration restriction and post-integration mutagenesis. After entering the nucleus, uracilated viral DNA products are degraded by the uracil base excision repair (UBER) machinery with less than 1% of the uracilated DNA successfully integrating. Although uracilated proviral DNA showed few mutations, the viral genomic RNA was highly mutated, suggesting that errors occur during transcription. Viral DNA isolated from blood monocytes and alveolar macrophages (but not T cells) of drug-suppressed HIV-infected individuals also contained abundant uracils. The presence of viral uracils in short-lived monocytes suggests their recent infection through contact with virus producing cells in a tissue reservoir. These findings reveal new elements of a viral defense mechanism involving host UBER that may be relevant to the establishment and persistence of HIV-1 infection.
Assuntos
Reparo do DNA , DNA Viral/metabolismo , HIV-1/genética , HIV-1/fisiologia , Macrófagos/virologia , Uracila/metabolismo , Integração Viral , Células Cultivadas , DNA Viral/genética , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Macrófagos/imunologia , Mutação , Transcrição ReversaRESUMO
OBJECTIVE: As survival with HIV infection improves, HIV-infected individuals appear to be susceptible to development of chronic diseases, including restrictive and obstructive lung diseases. We sought to determine the independent association of HIV infection on lung function decline. DESIGN: Longitudinal analysis of the AIDS Linked to the Intravenous Experience study, an observational cohort of current and former IDUs. METHODS: Generalized estimating equations were used to determine the effects of markers of HIV infection on adjusted annual change in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). RESULTS: A total of 1064 participants contributed 4555 spirometry measurements over a median follow-up time of 2.75 years. The mean age of the cohort was 48 years; nearly, two-thirds were men and 85% current smokers. After adjustment, the overall annual decline of FEV1 and FVC between HIV-infected and uninfected persons did not differ. However, there was a 76âml/year greater rate of decline in FEV1 and 86âml/year greater rate of decline in FVC among HIV-infected participants with viral load more than 75â000âcopies/ml compared with HIV-uninfected individuals (Pâ<â0.01). Similarly, HIV-infected individuals with CD4 cell count less than 100âcells/µl had a 57âml/year more rapid decline in FEV1 and 86âml/year more rapid decline in FVC than HIV-uninfected participants (Pâ=â0.018 and Pâ=â0.001, respectively). CONCLUSION: Markers of poorly controlled HIV disease are independently associated with accelerated annual lung function decline, with decrements in both FEV1 and FVC. These findings highlight the need for optimized HIV antiretroviral therapy in addition to smoking cessation among HIV-infected individuals with tobacco dependence.