Increased rate of FEV1 decline in HIV patients despite effective treatment with HAART

Autoři: Gloria Sampériz aff001;  Francisco Fanjul aff002;  Jose Luis Valera aff002;  Meritxell Lopez aff003;  Ángel Rios aff003;  María Peñaranda aff002;  Antoni Campins aff002;  Melchor Riera aff002;  Alvar Agusti aff004
Působiště autorů: Hospital Universitario Miguel Servet, Zaragoza, Spain aff001;  Hospital Universitari Son Espases, Palma de Mallorca, Spain aff002;  Institut d`Investigació Sanitària Illes Balears, Palma de Mallorca, Spain aff003;  Respiratory Institute, Hospital Clinic, IDIBAPS, Univ. Barcelona, Barcelona, Spain aff004;  CIBER Enfermedades Respiratorias, Palma de Mallorca, Spain aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224510



Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population.


We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere.


We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients.


Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population.

Klíčová slova:

Highly-active antiretroviral therapy – HIV – HIV infections – Marijuana – Medical risk factors – Pulmonary function – Smoking habits – Viral load


1. Vogelmeier CF, Criner GJ, Martinez FJ, Anzuelo A, Bames PJ, Celli BR et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Respirology. 2017;22(3):575–601. doi: 10.1111/resp.13012 28150362

2. Pefura-Yone EW, Fodjeu G, Kengne AP, Roche N, Kuaban C. Prevalence and determinants of chronic obstructive pulmonary disease in HIV infected patients in an African country with low level of tobacco smoking. Respir Med. 2015;109(2):247–254. doi: 10.1016/j.rmed.2014.12.003 25538018

3. Sampériz G, Guerrero D, López M, Valera JL, Iglesias A, Ríos A et al. Prevalence of and risk factors for pulmonary abnormalities in HIV-infected patients treated with antiretroviral therapy. HIV Med. 2014;15(6):321–329. doi: 10.1111/hiv.12117 24314004

4. Drummond MB, Kirk GD. HIV-associated obstructive lung diseases: insights and implications for the clinician. Lancet Respir Med. 2014;2(7):583–592. doi: 10.1016/S2213-2600(14)70017-7 24831854

5. Drummond MB, Kunisaki KM, Huang L. Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs. Semin Respir Crit Care Med. 2016;37(2):277–288. doi: 10.1055/s-0036-1578801 26974304

6. Twigg HL, Soliman DM, Day RB, Knox KS, Anderson RJ, Wilkes DS et al. Lymphocytic alveolitis, bronchoalveolar lavage viral load, and outcome in human immunodeficiency virus infection. Am J Respir Crit Care Med. 1999;159(5, Pt1):1439–1444.

7. Attia EF, Akgün KM, Wongtrakool C, Goetz MB, Rodriguez-Barradas MC, Rimland D et al. Increased risk of radiographic emphysema in HIV is associated with elevated soluble CD14 and nadir CD4. Chest. 2014;146(6):1543–1553. doi: 10.1378/chest.14-0543 25080158

8. Popescu I, Drummond MB, Gama L, Coon T, Merlo CA, Wise RA et al. Activation-induced cell death drives profound lung CD4(+) T-cell depletion in HIV-associated chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;190(7):744–755. doi: 10.1164/rccm.201407-1226OC 25137293

9. Morris A, Kingsley LA, Groner G, Lebedeva IP, Beard CB, Norris KA. Prevalence and clinical predictors of Pneumocystis colonization among HIV-infected men. AIDS. 2004;18(5):793–798. doi: 10.1097/00002030-200403260-00011 15075515

10. Morris A, Sciurba FC, Lebedeva IP, Githaiga A, Elliot WM, Hogg JC et al. Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am J Respir Crit Care Med. 2004;170(4):408–413. doi: 10.1164/rccm.200401-094OC 15117741

11. Lozupone C, Cota-Gomez A, Palmer BE, Linderman DJ, Charlson ES, Sodergren E et al. Lung HIV Microbiome Project. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med. 2013;187(10):1110–1117. doi: 10.1164/rccm.201211-2145OC 23392441

12. Pacht ER, Diaz P, Clanton T, Hart J, Gadek JE. Alveolar fluid glutathione decreases in asymptomatic HIV-seropositive subjects over time. Chest. 1997;112(3):785–788. doi: 10.1378/chest.112.3.785 9315816

13. Lassiter C, Fan X, Joshi PC, Jacob BA, Sutliff RL, Jones DP et al. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction. AIDS Res Ther. 2009; 6:1. doi: 10.1186/1742-6405-6-1 19193217

14. Lee FJ, Amin J, Carr A. Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and metaanalysis of 114 studies with up to 144 weeks follow-up. Plos One. 2014;15;9(5):e97482. doi: 10.1371/journal.pone.0097482 24830290

15. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. 2018; Available at:

16. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992;145(6):1321–1327. doi: 10.1164/ajrccm/145.6.1321 1595997

17. Fletcher CM. Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC Committee on the Aetiology of Chronic Bronchitis (MRC breathlessness score). BMJ. 1960;2:1662.

18. Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998; 158: 1789–1795. doi: 10.1001/archinte.158.16.1789 9738608

19. American Thoracic Society Official Statement. Standardization of Spirometry. 1994 Update. Am J Respir Crit Care Med. 1995;152:1107–1136. doi: 10.1164/ajrccm.152.3.7663792 7663792

20. Roca J, Sanchis J, Agustí-Vidal A, Segarra F, Navajas D, Rodriguez-Roisin R et al. Spirometric reference values for a mediterranean population. Bull Eur Physiopathol Respir. 1998; 22:217–224.

21. Roca J, Rodriguez-Roisín R, Cobo E, Burgos F, Perez J, Clausen JL. Single-breath carbon monoxide diffusing capacity (DLCO) prediction equations for a mediterranean population. Am Rev Respir Dis. 1990; 141:1026–1032. doi: 10.1164/ajrccm/141.4_Pt_1.1026 2327636

22. Clausen JL. Pulmonary function testing. Guidelines and controversies. Equipment, Methods and Normal Values. Orlando:Grune & Stratton, Inc., 1984. 338 pages.

23. ATS Statement: Guidelines for the Six-Minute Walk Test. Am J Respir Crit Care Med. 2002; 166 (1):111–117. doi: 10.1164/ajrccm.166.1.at1102 12091180

24. Kohansal R, Martinez-Camblor P, Agusti A, Buist AS, Mannino DM, Soriano JB. The Natural History of Chronic Airflow Obstruction Revisited: An Analysis of the Framingham Offspring Cohort. Am J Respir Crit Care Med. 2009:180:3–10. doi: 10.1164/rccm.200901-0047OC 19342411

25. Morris AM, Huang L, Bacchetti P, Turner J, Hopewell PC, Wallace JM et al. Permanent declines in pulmonary function following pneumonia in human immunodeficiency virus-infected persons. The Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med. 2000;162:612–616. doi: 10.1164/ajrccm.162.2.9912058 10934095

26. Drummond MB, Merlo CA, Astemborski J, Kalmin MM, Kisalu A, Mcdyer JF et al. The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort. AIDS. 2013;27(8):1303–1311. doi: 10.1097/QAD.0b013e32835e395d 23299176

27. Kunisaki KM, Niewoehner DE, Collins G, Aagaardd B, Atako NB, Bakowska E et al. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial. Lancet Respir Med. 2016: 4(12): 980–989. doi: 10.1016/S2213-2600(16)30319-8 27773665

28. Ronit A, Lundgren J, Afzal S, Benfield T, Roen A, Mocroft A et al. Airflow limitation in people living with HIV and matched uninfected controls. Thorax. 2018: 73(5): 431–438. doi: 10.1136/thoraxjnl-2017-211079 29331988

29. Jambo KC, Tembo DL, Kamng’ona AW, Musicha P, Banda DH, Kankwatira AM et al. HIV-associated disruption of lung cytokine networks is incompletely restored in asymptomatic HIV-infected Malawian adults on antiretroviral therapy. ERJ Open Res. 2017; 3: 00097–2017 doi: 10.1183/23120541.00097-2017 29255717

30. Triplette M, Attia EF, Akgun KM, Soo Hoo GW, Freiberg MS, Butt AA et al. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV. PLoS One. 2017:12(1):e0170857. doi: 10.1371/journal.pone.0170857 28122034

31. Mitchell DM, Fleming J, Pinching AJ, Harris JR, Moss FM, Veale D et al. Pulmonary function in human immunodeficiency virus infection. A prospective 18-month study of serial lung function in 474 patients. Am Rev Respir Dis. 1992;146:745–751. doi: 10.1164/ajrccm/146.3.745 1519857

32. Joshi PC, Guidot DM. The alcoholic lung: epidemiology, pathophysiology, and potential therapies. American Journal of Physiology—Lung Cellular and Molecular Physiology. 2007:292(4):L813–L823. doi: 10.1152/ajplung.00348.2006 17220370

33. Frantz S, Wollmer P, Dencker M, Engdtröm G, Nihlén U. Associations between lung function and alcohol consumption—assessed by both a questionnaire and a blood marker. Respir Med. 2014:108(1):114–121. doi: 10.1016/j.rmed.2013.08.041 24064346

34. Berry CE, Drummond MB. The Horse-Racing Effect and Lung Function: Can We Slow the Fastest Horse? Am J Respir Crit Care Med. 2017:195(9):1134–1135. doi: 10.1164/rccm.201703-0540ED 28459329

35. Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P et al. Changes in Forced Expiratory Volume in 1 Second over Time in COPD. N Engl J Med. 2011:365(13):1184–1192. doi: 10.1056/NEJMoa1105482 21991892

36. Lange P, Celli B, Agusti A, Jensen GB, Divo M, Faner R et al. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. N Engl J Med. 2015:373(2):111–12. doi: 10.1056/NEJMoa1411532 26154786

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2019 Číslo 10