Increased risk of bacterial pneumonia in HIV-infected intravenous drug users without AIDS

Selwyn, Peter A.; Feingold, Anat R.; Hartel, Diana; Schoenbaum, Ellie E.; Alderman, Michael H.; Klein, Robert S.; Friedland, Gerald

doi:10.1097/00002030-198808000-00005

Cited by 211 publications

(56 citation statements)

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“…HIV-infected drug abusers have a higher incidence of pneumococcal pneumonia contributing to the morbidity and mortality observed in this population. HIV-seropositive injection drug users are at an ϳ4-fold greater risk of pneumococcal pneumonia than their HIV-seropositive nondrug-using counterparts (5,6). These data suggest that drug abuse is a vital risk factor for pneumococcal infections.…”

Section: Mmunocompromise Resulting From Prolonged Drug Use Contribumentioning

confidence: 87%

Morphine Induces Defects in Early Response of Alveolar Macrophages to Streptococcus pneumoniae by Modulating TLR9-NF-κB Signaling

Wang

Barke

Charboneau

et al. 2008

The Journal of Immunology

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Resident alveolar macrophages and respiratory epithelium constitutes the first line of defense against invading lung pneumococci. Results from our study showed that increased mortality and bacterial outgrowth and dissemination seen in morphine-treated mice were further exaggerated following depletion of alveolar macrophages with liposomal clodronate. Using an in vitro alveolar macrophages and lung epithelial cells infection model, we show significant release of MIP-2 from alveolar macrophages, but not from lung epithelial cells, following 4 h of exposure of cells to pneumococci infection. Morphine treatment reduced MIP-2 release in pneumococci stimulated alveolar macrophages. Furthermore, morphine treatment inhibited Streptococcus pneumoniae-induced NF-κB-dependent gene transcription in alveolar macrophages following 2 h of in vitro infection. S. pneumoniae infection resulted in a significant induction of NF-κB activity only in TLR9 stably transfected HEK 293 cells, but not in TLR2 and TLR4 transfected HEK 293 cells, and morphine treatment inhibited S. pneumoniae-induced NF-κB activity in these cells. Moreover, morphine treatment also decreased bacterial uptake and killing in alveolar macrophages. Taken together, these results suggest that morphine treatment impairs TLR9-NF-κB signaling and diminishes bacterial clearance following S. pneumoniae infection in resident macrophages during the early stages of infection, leading to a compromised innate immune response.

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Section: Mmunocompromise Resulting From Prolonged Drug Use Contribumentioning

confidence: 87%

Morphine Induces Defects in Early Response of Alveolar Macrophages to Streptococcus pneumoniae by Modulating TLR9-NF-κB Signaling

Wang

Barke

Charboneau

et al. 2008

The Journal of Immunology

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“…Bacterial pneumonia is well known to occur at excess rates in persons with HIV infection (1)(2)(3)(4)(5). Since the early years of the HIV epidemic, high rates of bacterial infections were reported in patients with AIDS and HIV infection (1-3, 6, 7).…”

mentioning

confidence: 99%

“…Even a single episode of bacterial pneumonia is associated with substantial morbidity and mortality (2)(3)(4)(5)(6)9).…”

mentioning

confidence: 99%

Pneumonia in HIV-infected Persons

Gordin¹,

Roediger²,

Girard

et al. 2008

Am J Respir Crit Care Med

101

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Rationale: Bacterial pneumonia is a major cause of morbidity for HIVinfected persons and contributes to excess mortality in this population. Objectives: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy. Methods: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee. Measurements and Main Results: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P 5 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P 5 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not. Conclusions: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status. Clinical trial registered with www.clinicaltrials.gov (NCT 00027352).

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“…Rates of bacterial pneumonia in HIV-infected adults are increased 5±10-fold compared with age-matched controls [90,94,105,106] (Table 4). In these groups the environmental and social problems that exist and predispose to increased rates of disease in the HIV-uninfected population are simply compounded by infection with HIV.…”

Section: Epidemiology Of S Pneumoniae and Hiv Infectionmentioning

confidence: 99%