Share this article on:

High Frequency of Hypothalamic-Pituitary-Adrenal Axis Dysfunction After Local Corticosteroid Injection in HIV-Infected Patients on Protease Inhibitor Therapy

Hyle, Emily P. MD*,†; Wood, Brian R. MD‡,§; Backman, Elke S. PharmD; Noubary, Farzad PhD*,¶; Hwang, Janice MD#,**; Lu, Zhigang MD*,††; Losina, Elena PhD*,‡‡,§§; Walensky, Rochelle P. MD, MPH*,†,§,‡‡; Gandhi, Rajesh T. MD†,‖‖

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2013 - Volume 63 - Issue 5 - p 602–608
doi: 10.1097/QAI.0b013e31829b662b
Clinical Science

Background: The frequency of hypothalamic-pituitary-adrenal axis dysfunction among HIV-infected patients receiving steroid injections has not been reported, and the risk factors for this adverse event are poorly characterized.

Methods: We conducted a retrospective analysis of data from HIV-infected patients in the Partners HealthCare system (Boston, MA) who received corticosteroid injection(s) between 2002 and 2011. Chart review focused on HIV status, antiretroviral therapy [eg, protease inhibitors (PI)], steroid injection(s), and adrenal axis dysfunction (eg, adrenal insufficiency and/or Cushing syndrome). Because all cases occurred among patients on PIs, we performed additional detailed data extraction and conducted univariate and multivariate analyses to identify risk factors in this group.

Results: One hundred seventy-one HIV-infected patients received ≥1 corticosteroid injection(s) in the study period. Nine cases (event frequency: 5.3%; 95% confidence interval: 2.4% to 9.8%) of secondary adrenal insufficiency were diagnosed; 5 (55%) of these 9 patients also had clinical evidence of Cushing syndrome. All cases occurred among the 81 patients on PIs (event frequency among those on PIs: 11.1%; 95% confidence interval: 5.2% to 20.0%). Among patients on PIs, the major risk factor for hypothalamic-pituitary-adrenal axis dysfunction was having ≥2 injections within 6 months.

Conclusions: In this retrospective cohort study, 11% of HIV-infected patients on PIs at the time of steroid injection were later diagnosed with hypothalamic-pituitary-adrenal axis dysfunction. Corticosteroid injections in HIV-infected patients on PIs should only be used with great caution and close monitoring.

*Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA;

Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA;

Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA;

§Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA;

Department of Pharmacy, Massachusetts General Hospital, Boston, MA;

Research Design Center/Biostatistics Research Center, Clinical and Translational Science Institute, Tufts University, Boston, MA;

#Division of Endocrinology, Yale University School of Medicine, New Haven, CT;

**Division of Endocrinology, Massachusetts General Hospital, Boston, MA;

††Department of Newborn Medicine, Brigham and Women's Hospital, Boston, MA;

‡‡Harvard University Center for AIDS Research, Boston, MA;

§§Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA; and

‖‖Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Charlestown, MA.

Correspondence to: Emily P. Hyle, MD, Division of Infectious Diseases, Massachusetts General Hospital, 50 Staniford Street, 9th Floor, Boston, MA 02114-2696 (e-mail:

E.P.H. is supported by National Institute of Allergy and Infectious Disease [T32 AI 007433]. R.T.G. is supported by National Institutes of Health (NIH) [R01 AI066992-04A1] and NIH G08LM008830-01 and by grants to the AIDS Clinical Trials Group (NIH U01 AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06). This publication was made possible with help from the Harvard University Center for AIDS Research (CFAR), an NIH-funded program (P30 AI060354), which is supported by the following NIH co-funding and participating institutes and centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR.

R.T.G. has received grant support from Tibotec (now Janssen), Abbott, and Viiv.

Received February 20, 2013

Accepted May 09, 2013

© 2013 by Lippincott Williams & Wilkins