Pulmonary Infections in Patients with Human Immunodeficiency Virus Infection

Catia Cilloniz; Juan M. Pericàs; José M. Miró; Antoni Torres

doi:10.1055/a-2725-7350

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med
DOI: 10.1055/a-2725-7350

Review Article

Pulmonary Infections in Patients with Human Immunodeficiency Virus Infection

Authors

Catia Cilloniz

¹August Pi i Sunyer Biomedical Research Institute–IDIBAPS, Barcelona, Spain

²Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain

³Faculty of Health Sciences, Continental University, Huancayo, Peru
Juan M. Pericàs

⁴Liver Unit, Division of Digestive Diseases, Vall d'Hebron University Hospital, Barcelona, Spain

⁵Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain

⁶Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

⁷Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
José M. Miró

⁸HIV Unit, Infectious Disease Department, Hospital Clínic-IDIBAPS, Barcelona, Spain

⁹CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain

¹⁰University of Barcelona, Barcelona, Spain

¹¹Reial Academia de Medicina de Catalunya, Barcelona, Spain
Antoni Torres

¹August Pi i Sunyer Biomedical Research Institute–IDIBAPS, Barcelona, Spain

²Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain

¹⁰University of Barcelona, Barcelona, Spain

Abstract

Pulmonary infection is an important cause of hospitalization, morbidity, and mortality in people living with human immunodeficiency virus (HIV; PWH) infection, especially in those with significant immunosuppression. Pneumonia, including Pneumocystis jirovecii and Mycobacterium tuberculosis etiologies, continues to be the most frequent pulmonary infection in PWH. However, identifying the etiology of pulmonary infection in PWH is challenging because of the overlap in clinical features and the frequency of co-infection. This review focuses on the current scientific evidence regarding pulmonary infection in PWH, including its epidemiology, clinical presentation, diagnosis, and management.

Keywords

pulmonary infection - human immunodeficiency virus - antiretroviral therapy

Full Text

References

References
1 UNAIDS data. 2024 | UNAIDS. Accessed October 28, 2025 at: https://www.unaids.org/en/resources/documents/2024/2024_unaids_data
2 Balakrishna S, Wolfensberger A, Kachalov V. et al; Swiss HIV Cohort Study. Decreasing incidence and determinants of bacterial Pneumonia in people with HIV: the Swiss HIV Cohort Study. J Infect Dis 2022; 225 (09) 1592-1600
3 2024 global AIDS report—The Urgency of Now: AIDS at a Crossroads | UNAIDS. Accessed October 28, 2025 at: https://www.unaids.org/en/resources/documents/2024/global-aids-update-2024
4 Global HIV & AIDS statistics—Fact sheet | UNAIDS. Accessed October 28, 2025 at: https://www.unaids.org/en/resources/fact-sheet
5 Wolder Ejlersen E, Loft JA, Gelpi M. et al. Incidence of confirmed influenza and Pneumococcal infections and vaccine uptake among virologically suppressed people living with HIV. Vaccines (Basel) 2025; 13 (04) 358
6 De P, Farley A, Lindson N, Aveyard P. Systematic review and meta-analysis: influence of smoking cessation on incidence of pneumonia in HIV. BMC Med 2013; 11: 15
7 Richards GA, Zamparini J, Kalla I. et al. Critical illness due to infection in people living with HIV. Lancet HIV 2024; 11 (06) e406-e418
8 Cillóniz C, Dominedò C, Álvarez-Martínez MJ. et al. Pneumocystis pneumonia in the twenty-first century: HIV-infected versus HIV-uninfected patients. Expert Rev Anti Infect Ther 2019; 17 (10) 787-801
9 Moir S, Buckner CM, Ho J. et al. B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy. Blood 2010; 116 (25) 5571-5579
10 Boyd MA, van Bockel D, Munier CML, Kelleher AD. Navigating the complexity of chronic HIV-1 associated immune dysregulation. Curr Opin Immunol 2022; 76: 102186
11 Justice AC, Goetz MB, Stewart CN. et al. Delayed presentation of HIV among older individuals: a growing problem. Lancet HIV 2022; 9 (04) e269-e280
12 Cilloniz C, Dy-Agra G, Pagcatipunan Jr RS, Torres A. Viral Pneumonia: from influenza to COVID-19. Semin Respir Crit Care Med 2024; 45 (02) 207-224
13 Garcia Garrido HM, Mak AMR, Wit FWNM. et al. Incidence and risk factors for invasive pneumococcal disease and community-acquired Pneumonia in human immunodeficiency virus-infected individuals in a high-income setting. Clin Infect Dis 2020; 71 (01) 41-50
14 Venturas JP, Richards GA, Feldman C. Severe community-acquired pneumonia at a tertiary academic hospital in Johannesburg, South Africa. Respir Med 2024; 234: 107823
15 Maphula RW, Laher AE, Richards GA. Patterns of presentation and survival of HIV-infected patients admitted to a tertiary-level intensive care unit. HIV Med 2020; 21 (05) 334-341
16 Pulsipher AM, Vikram HR, Gotway MB. et al. An observational analysis of a large cohort of Pneumocystis jirovecii Pneumonia. Open Forum Infect Dis 2025; 12 (07) ofaf390
17 Kolbrink B, Scheikholeslami-Sabzewari J, Borzikowsky C. et al. Evolving epidemiology of pneumocystis pneumonia: findings from a longitudinal population-based study and a retrospective multi-center study in Germany. Lancet Reg Health Eur 2022; 18: 100400
18 Tuberculosis (TB). Accessed October 28, 2025 at: https://www.who.int/news-room/fact-sheets/detail/tuberculosis
19 Zhang S-X, Wang J-C, Yang J. et al. Epidemiological features and temporal trends of the co-infection between HIV and tuberculosis, 1990-2021: findings from the global burden of disease study 2021. Infect Dis Poverty 2024; 13 (01) 59
20 Cillóniz C, García-Vidal C, Moreno A, Miro JM, Torres A. Community-acquired bacterial pneumonia in adult HIV-infected patients. Expert Rev Anti Infect Ther 2018; 16 (07) 579-588
21 Crothers K, Huang L, Goulet JL. et al. HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era. Am J Respir Crit Care Med 2011; 183 (03) 388-395
22 Melliez H, Mary-Krause M, Guiguet M. et al. Risk of severe bacterial infection in people living human immunodeficiency virus infection in the combined antiretroviral therapy era. J Infect Dis 2020; 222 (05) 765-776
23 Attia EF, McGinnis KA, Feemster LC. et al. Association of COPD with risk for pulmonary infections requiring hospitalization in HIV-infected Veterans. J Acquir Immune Defic Syndr 2015; 70 (03) 280-288
24 Johnston PI, Wright SW, Orr M. et al. Worldwide relative smoking prevalence among people living with and without HIV. AIDS 2021; 35 (06) 957-970
25 De Socio GV, Pasqualini M, Ricci E. et al; CISAI study group. Smoking habits in HIV-infected people compared with the general population in Italy: a cross-sectional study. BMC Public Health 2020; 20 (01) 734
26 Tron L, Lert F, Spire B, Dray-Spira R. ANRS-Vespa2 study group. Tobacco smoking in HIV-infected versus general population in France: heterogeneity across the various groups of people living with HIV. PLoS One 2014; 9 (09) e107451
27 Ahlström MG, Knudsen A, Ullum H. et al. Association between smoking status assessed with plasma-cotinine and inflammatory and endothelial biomarkers in HIV-positive and HIV-negative individuals. HIV Med 2018; 19 (10) 679-687
28 Baskaran V, Murray RL, Hunter A, Lim WS, McKeever TM. Effect of tobacco smoking on the risk of developing community acquired pneumonia: a systematic review and meta-analysis. PLoS One 2019; 14 (07) e0220204
29 Poudel KC, Poudel-Tandukar K, Bertone-Johnson ER, Pekow P, Vidrine DJ. Inflammation in relation to intensity and duration of cigarette smoking among people living with HIV. AIDS Behav 2021; 25 (03) 856-865
30 Nieman RB, Fleming J, Coker RJ, Harris JR, Mitchell DM. The effect of cigarette smoking on the development of AIDS in HIV-1-seropositive individuals. AIDS 1993; 7 (05) 705-710
31 Brown JL, Winhusen T, DiClemente RJ. et al. The association between cigarette smoking, virologic suppression, and CD4+ lymphocyte count in HIV-Infected Russian women. AIDS Care 2017; 29 (09) 1102-1106
32 Winhusen T, Feaster DJ, Duan R. et al. Baseline cigarette smoking status as a predictor of virologic suppression and CD4 cell count during one-year follow-up in substance users with uncontrolled HIV infection. AIDS Behav 2018; 22 (06) 2026-2032
33 Konstantinidis I, Crothers K, Kunisaki KM. et al. HIV-associated lung disease. Nat Rev Dis Primers 2023; 9 (01) 39
34 Kershaw CD, Guidot DM. Alcoholic lung disease. Alcohol Res Health 2008; 31 (01) 66-75
35 Jung MK, Callaci JJ, Lauing KL. et al. Alcohol exposure and mechanisms of tissue injury and repair. Alcohol Clin Exp Res 2011; 35 (03) 392-399
36 Szabo G, Saha B. Alcohol's effect on host defense. Alcohol Res 2015; 37 (02) 159-170
37 Jolley SE, Alkhafaf Q, Hough C, Welsh DA. Presence of an alcohol use disorder is associated with greater pneumonia severity in hospitalized HIV-infected patients. Lung 2016; 194 (05) 755-762
38 Reynolds PM, Afshar M, Wright GC. et al. Association between substance misuse and outcomes in critically iii patients with Pneumonia. Ann Am Thorac Soc 2023; 20 (04) 556-565
39 Haw NJL, Lesko CR, Ng DK. et al; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Incidence of non-AIDS defining comorbidities among young adults with perinatally acquired HIV in North America. AIDS 2024; 38 (09) 1366-1374
40 Zhabokritsky A, Klein M, Loutfy M. et al. Non-AIDS-defining comorbidities impact health related quality of life among older adults living with HIV. Front Med (Lausanne) 2024; 11: 1380731
41 Community-Acquired Pneumonia. Adult and Adolescent OIs | NIH. 2022 ; Accessed October 28, 2025 at: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/community-acquired
42 Cilloniz C, Torres A, Polverino E. et al. Community-acquired lung respiratory infections in HIV-infected patients: microbial aetiology and outcome. Eur Respir J 2014; 43 (06) 1698-1708
43 Andrews B. Surviving sepsis in high HIV prevalence settings. Med J Zambia 2010; 37 (02) 104-110
44 Wiewel MA, Huson MA, van Vught LA. et al; MARS Consortium. Impact of HIV infection on the presentation, outcome and host response in patients admitted to the intensive care unit with sepsis; a case control study. Crit Care 2016; 20 (01) 322
45 Chew KW, Yen IH, Li JZ, Winston LG. Predictors of pneumonia severity in HIV-infected adults admitted to an urban public hospital. AIDS Patient Care STDs 2011; 25 (05) 273-277
46 Camon S, Quiros C, Saubi N. et al. Full blood count values as a predictor of poor outcome of pneumonia among HIV-infected patients. BMC Infect Dis 2018; 18 (01) 189
47 Tilahun M, Gebretsadik D, Seid A. et al. Bacteriology of community-acquired pneumonia, antimicrobial susceptibility pattern and associated risk factors among HIV patients, Northeast Ethiopia: cross-sectional study. SAGE Open Med 2023;11:20503121221145569
48 Schleenvoigt BT, Ankert J, Barten-Neiner G. et al; CAPNETZ Study Group. Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-cohort. Infection 2024; 52 (01) 129-137
49 Ochoa-Gondar O, Torras-Vives V, de Diego-Cabanes C. et al. Incidence and risk factors of pneumococcal pneumonia in adults: a population-based study. BMC Pulm Med 2023; 23 (01) 200
50 Cillóniz C, Torres A, Manzardo C. et al. Community-acquired Pneumococcal Pneumonia in virologically suppressed HIV-infected adult patients: a matched case-control study. Chest 2017; 152 (02) 295-303
51 Albrich WC, Madhi SA, Adrian PV. et al. Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia. BMJ Open 2014; 4 (08) e005953
52 Swathirajan CR, Rameshkumar MR, Solomon SS, Vignesh R, Balakrishnan P. Changing drug resistance profile in Pseudomonas aeruginosa infection among HIV patients from 2010-2017: a retrospective study. J Glob Antimicrob Resist 2019; 16: 274-277
53 Allen SH, Brennan-Benson P, Nelson M. et al. Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas aeruginosa in the HAART era. Postgrad Med J 2003; 79 (938) 691-694
54 Wooten DA, Winston LG. Risk factors for methicillin-resistant Staphylococcus aureus in patients with community-onset and hospital-onset pneumonia. Respir Med 2013; 107 (08) 1266-1270
55 Torres A, Cilloniz C, Niederman MS. et al. Pneumonia. Nat Rev Dis Primers 2021; 7 (01) 25
56 Cillóniz C, Miguel-Escuder L, Pedro-Bonet ML. et al; Legionella-HIV Researchers. Community-acquired Legionella Pneumonia in human immunodeficiency virus-infected adult patients: a matched case-control study. Clin Infect Dis 2018; 67 (06) 958-961
57 Figueiredo-Mello C, Naucler P, Negra MD, Levin AS. Prospective etiological investigation of community-acquired pulmonary infections in hospitalized people living with HIV. Medicine (Baltimore) 2017; 96 (04) e5778
58 Bai AD, Srivastava S, Martinez Cajas JL, Razak F, Verma AA. Community-acquired Pneumonia in people with HIV during the current era of effective antiretroviral therapy: a multicenter retrospective cohort study. Clin Infect Dis 2025; 80 (02) 397-403
59 Christensen D, Feldman C, Rossi P. et al; Community-Acquired Pneumonia Organization Investigators. HIV infection does not influence clinical outcomes in hospitalized patients with bacterial community-acquired pneumonia: results from the CAPO international cohort study. Clin Infect Dis 2005; 41 (04) 554-556
60 Malinis M, Myers J, Bordon J. et al. Clinical outcomes of HIV-infected patients hospitalized with bacterial community-acquired pneumonia. Int J Infect Dis 2010; 14 (01) e22-e27
61 Venturas JP, Titus A, Richards GA, Feldman C. Severe community-acquired Pneumonia: impact of HIV on Clinical presentation, microbiological and laboratory findings, and outcome. J Intensive Care Med 2025; 40 (11) 1204-1213
62 Tan B, Webster H, Krishnaswamy S, MacPhail A, Pilcher D. Outcomes of critical illness in peoples with Advanced HIV Disease: 30 years of binational data. Clin Infect Dis 2025; ciaf362
63 Søgaard OS, Lohse N, Gerstoft J. et al. Mortality after hospitalization for pneumonia among individuals with HIV, 1995-2008: a Danish cohort study. PLoS One 2009; 4 (09) e7022
64 Restrepo MI, Faverio P, Anzueto A. Long-term prognosis in community-acquired pneumonia. Curr Opin Infect Dis 2013; 26 (02) 151-158
65 Bordon J, Kapoor R, Martinez C. et al. CD4+ cell counts and HIV-RNA levels do not predict outcomes of community-acquired pneumonia in hospitalized HIV-infected patients. Int J Infect Dis 2011; 15 (12) e822-e827
66 Zifodya JS, Duncan MS, So-Armah KA. et al. Community-acquired Pneumonia and risk of cardiovascular events in people living with HIV. J Am Heart Assoc 2020; 9 (23) e017645
67 Sarkar P, Rasheed HF. Clinical review: respiratory failure in HIV-infected patients–a changing picture. Crit Care 2013; 17 (03) 228
68 Salwen B, Mascarenhas E, Horne DJ, Crothers K, Zifodya JS. Sequelae of immunocompromised host Pneumonia. Clin Chest Med 2025; 46 (01) 49-60
69 Uranga A, España PP. Long-term mortality in community-acquired Pneumonia. Arch Bronconeumol (Engl Ed) 2018; 54 (08) 412-413
70 Health NI of. Prevention C for DC and, Council (OARAC) HMA of the IDS of AP on G for the P and T of OI in A and A with H-AWG of the O of ARA. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. ClinicalInfoHIV.gov [Internet] US Department of Health and Human Services; 2025 . Accessed October 28, 2025 at: https://www.ncbi.nlm.nih.gov/books/NBK586304/
71 CDC. Interim Clinical Considerations for Use of COVID-19 Vaccines in the United States. COVID 2025;19. at Accessed October 28, 2025 at: https://www.cdc.gov/covid/hcp/vaccine-considerations/index.html
72 Liu Y, Su L, Jiang S-J, Qu H. Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget 2017; 8 (35) 59729-59739
73 Wakefield AE, Lindley AR, Ambrose HE, Denis C-M, Miller RF. Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients. J Infect Dis 2003; 187 (06) 901-908
74 Liu Y, Fahle GA, Kovacs JA. Inability to culture Pneumocystis jirovecii. MBio 2018; 9 (03) e00939-e18
75 Giacobbe DR, Dettori S, Di Pilato V. et al; JIR-ICU Investigators (Collaborators), the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESGCIP), and the Fungal Infections Study Group of the European Society of Clinical Microbiology and Infectious Diseases (EFISG), JIR-ICU investigators (collaborators). Mortality of Pneumocystis jirovecii pneumonia in intensive care units: a post-hoc analysis of an international multicenter study by ESGCIP and EFISG. Ann Med 2025; 57 (01) 2511043
76 Ahmadpour E, Valilou S, Ghanizadegan MA. et al. Global prevalence, mortality, and main characteristics of HIV-associated pneumocystosis: a systematic review and meta-analysis. PLoS One 2024; 19 (03) e0297619
77 Limper AH, Adenis A, Le T, Harrison TS. Fungal infections in HIV/AIDS. Lancet Infect Dis 2017; 17 (11) e334-e343
78 Roux A, Canet E, Valade S. et al. Pneumocystis jirovecii pneumonia in patients with or without AIDS, France. Emerg Infect Dis 2014; 20 (09) 1490-1497
79 Liu C-J, Lee T-F, Ruan S-Y, Yu C-J, Chien J-Y, Hsueh P-R. Clinical characteristics, treatment outcomes, and prognostic factors of Pneumocystis pneumonia in non-HIV-infected patients. Infect Drug Resist 2019; 12: 1457-1467
80 Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. J Infect Chemother 2007; 13 (01) 1-7
81 Tasaka S, Tokuda H, Sakai F. et al. Comparison of clinical and radiological features of pneumocystis pneumonia between malignancy cases and acquired immunodeficiency syndrome cases: a multicenter study. Intern Med 2010; 49 (04) 273-281
82 Ebner L, Walti LN, Rauch A. et al. Clinical course, radiological manifestations, and outcome of Pneumocystis jirovecii Pneumonia in HIV patients and renal transplant recipients. PLoS One 2016; 11 (11) e0164320
83 Kanne JP, Yandow DR, Meyer CA. Pneumocystis jiroveci pneumonia: high-resolution CT findings in patients with and without HIV infection. AJR Am J Roentgenol 2012; 198 (06) W555-61
84 Azoulay E, Russell L, Van de Louw A. et al; Nine-i Investigators. Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med 2020; 46 (02) 298-314
85 Scharmann U, Kirchhoff L, Buer J. et al. Evaluation of the loop-mediated isothermal amplification assay (LAMP) Eazyplex Pneumocystis jirovecii. J Fungi (Basel) 2025; 11 (04) 300
86 Esteves F, Calé SS, Badura R. et al. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers. Clin Microbiol Infect 2015; 21 (04) 379.e1-379.e10
87 Jaramillo Cartagena A, Asowata OE, Ng D, Babady NE. An overview of the laboratory diagnosis of Pneumocystis jirovecii pneumonia. J Clin Microbiol 2025; 63 (03) e0036124
88 Schmidt JJ, Lueck C, Ziesing S. et al. Clinical course, treatment and outcome of Pneumocystis pneumonia in immunocompromised adults: a retrospective analysis over 17 years. Crit Care 2018; 22 (01) 307
89 Kamel T, Janssen-Langenstein R, Quelven Q. et al; PCP-MULTI Study group. Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study. Intensive Care Med 2024; 50 (08) 1228-1239
90 Elango K, Mudgal M, Murthi S. et al. Trends in the epidemiology and outcomes of pneumocystis pneumonia among human immunodeficiency virus (HIV) hospitalizations. Int J Environ Res Public Health 2022; 19 (05) 2768
91 Bares SH, Swindells S. Latent tuberculosis and HIV infection. Curr Infect Dis Rep 2020; 22: 17
92 Mycobacterium tuberculosis: Adult and Adolescent OIs | NIH. 2024 . Accessed October 28, 2025 at: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium
93 Lewinsohn DM, Leonard MK, LoBue PA. et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64 (02) 111-115
94 Oda G, Lucero-Obusan C, Schirmer P, Chung J, Holodniy M. Risk factors for extrapulmonary tuberculosis among US veterans, 1990-2022. Open Forum Infect Dis 2024; 11 (12) ofae698
95 CDC. Clinical Overview of Tuberculosis Disease. Tuberculosis (TB) 2025. Accessed October 28, 2025 at: https://www.cdc.gov/tb/hcp/clinical-overview/tuberculosis-disease.html
96 WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection, 2021 update. Accessed October 28, 2025 at: https://www.who.int/publications/i/item/9789240029415
97 CDC. Updated Guidelines on the Treatment of Drug-Susceptible and Drug-Resistant TB. Tuberculosis (TB) 2025. Accessed October 28, 2025 at: https://www.cdc.gov/tb/php/dear-colleague-letters/2025-treatment-guidelines.html
98 Saukkonen JJ, Duarte R, Munsiff SS. et al. Updates on the treatment of drug-susceptible and drug-resistant tuberculosis: an official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med 2025; 211 (01) 15-33
99 WHO consolidated guidelines on tuberculosis Module 1: prevention - tuberculosis preventive treatment, second edition. Accessed October 28, 2025 at: https://www.who.int/publications/i/item/9789240096196