Treating Adults With HIV In The Emergency Room: HAART Side Effects, Opportunistic Infections, Viral Load, CD4 Counts | EB Medicine 2016

The HIV-Infected Adult Patient in the Emergency Department: The Changing Landscape of Disease (Pharmacology CME)

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Table of Contents
Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Selected Abbreviations
  5. Critical Appraisal of the Literature
  6. Epidemiology And Pathophysiology
  7. Prehospital Care
  8. Emergency Department Evaluation
    1. History
    2. Physical Examination
  9. Diagnostic Testing
    1. Laboratory Testing
  10. Medication Side Effects
    1. Highly Active Antiretroviral Therapy
      1. Nucleoside Reverse Transcriptase Inhibitors And Nucleotide Reverse Transcriptase Inhibitors
      2. Nonnucleoside Reverse Transcriptase Inhibitors
      3. Protease Inhibitors
      4. Integrase Inhibitors
      5. Fusion Inhibitors
  11. System-Based Disease And Medication Effects
    1. Cardiovascular Disease
    2. Pulmonary Disease
    3. Renal Disease
    4. Neurologic Disease
    5. Gastrointestinal And Hepatobiliary Disease
    6. Hematologic Disease
    7. Endocrine Disease
    8. Musculoskeletal Disease
    9. Psychiatric Disease
    10. Dermatologic Disease
  12. Special Circumstances
  13. Summary
  14. Key Points
  15. Case Conclusions
  16. Acknowledgement
  17. Clinical Pathway For Management Of Weakness In HIV-Infected Patients
  18. Tables and Figures
    1. Table 1. Major Adverse Effects Of Antiretroviral Medications
    2. Figure 1. Chest X-Ray Of Pneumocystis jiroveci Pneumonia
  19. References


The care of the HIV-infected patient in the emergency department has changed since the development of highly active antiretroviral therapy. This therapy has resulted in longer life expectancies and increased quality of life for HIV-infected patients, and in cases of treatment compliance and success, virtual elimination of AIDS-associated opportunistic infections. As a result, the emergency clinician is now more often confronted with adverse events related to medication and the diseases associated with aging and chronic disease. This issue focuses on the differences in evaluation of HIV patients on long-term therapy and patients with medication noncompliance and low CD4 counts, as well as recognition of life-threatening and rare opportunistic infections. Disease processes related to the effect of longstanding HIV infection, even with good control, on many organ systems are addressed.

Case Presentations

You arrive for your ED shift and are presented with 3 HIV-infected patients with various chief complaints. The first patient is a 28-year-old man with 1 day of right flank pain, nausea, vomiting, and hematuria. He had a kidney stone a year ago with identical pain, and a point-of-care ultrasound shows asymmetric hydronephrosis; however, a nonenhanced CT scan demonstrates hydronephrosis and hydroureter without a stone. You wonder if the CT eliminates an impacted stone or if there is another explanation.

The second patient is a 42-year-old HIV-infected woman complaining of as many as 3 episodes a day of diarrhea for the past 3 weeks. She denies pain, melena, rectal bleeding, and fevers. Her laboratory test results are unremarkable. You wonder if additional testing is needed and whether sending her home is appropriate.

The third patient presents because her family has noticed that she has been acting increasingly “sad.” She denies any suicidal or homicidal ideation, but does corroborate that since initiation of an SSRI antidepressant drug 6 months ago, she has not noticed any improvement in her mood. In the absence of suicidal ideation, you wonder if she can be sent home.

You are reminded that caring for the HIV-infected patient is not so simple, and you realize quickly that you are dealing with 3 very different presentations related to the same disease and must prioritize where to begin.


The human immunodeficiency virus (HIV) causes a progressive failure of the immune system, ultimately leading to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. Although under different nomenclature, AIDS was first described in the early 1980s when clusters of patients developed opportunistic infections (OIs) not seen in patients with intact immune systems. HIV has spread to every country in the world, creating a global pandemic. In 2012, there were 35.3 million people living with HIV worldwide and 2.3 million new diagnoses that year.1

The development of highly active antiretroviral therapy (HAART) in 1996 dramatically increased life expectancy for HIV-infected patients. Due to the effectiveness of HAART, by the early 2000s, life expectancy of HIV-infected patients in developed countries was equivalent to that of comparable persons who were not HIV-infected.2,3

Current guidelines from the United States Department of Health and Human Services recommend the treatment of all HIV-infected patients with antiretroviral medications (ARVs).4 These current recommendations are based on evidence that ARVs reduce the risk of disease progression in all patients with CD4 T lymphocyte (CD4) count < 350 cells/mm3, CD4 count 350 to 500 cells/mm3, and CD4 count > 500 cells/mm3. This recommendation is a change from prior guidelines, which recommended therapy only for patients with lower CD4 counts. The guidelines are also based on evidence that treatment decreases the risk of transmission, and that patients with undetectable HIV viral loads are at exceedingly low risk for transmitting the virus to others.5

In addition to improving life expectancy, HAART has also changed the epidemiology of conditions affecting HIV-infected patients. In the beginning of the epidemic, HIV patients generally presented with infectious complications of their advanced disease. These included OIs such as Pneumocystis jiroveci pneumonia and Kaposi sarcoma. Now, patients more commonly present with complications unrelated to OIs, including cardiovascular, hepatic, and kidney disease, as well as HIV-related malignancies and adverse effects from medication.5,6 The spectrum of presenting complaints is associated with patient compliance with treatment. OIs are still seen in patients with undiagnosed infection presenting with advanced disease and those with financial, social, or other barriers to medication compliance.

This changing epidemiology of HIV complications poses a particular challenge for emergency clinicians, who should be familiar with these presentations as well as the presentation of OIs. This issue of Emergency Medicine Practice reviews the emergency complications of long-term HIV infection, especially noninfectious conditions and complications common in the HAART-adherent HIV patient.

Selected Abbreviations

AIDS: Acquired immunodeficiency syndrome

ARV: Antiretroviral

AZT/ZDV: Zidovudine

HAART: Highly active antiretroviral therapy

HIV: Human immunodeficiency virus

NNRTI: Nonnucleoside reverse transcriptase inhibitor

NRTI: Nucleoside reverse transcriptase inhibitor

NtRTI: Nucleotide reverse transcriptase inhibitor

OI: Opportunistic infection

PEP: Postexposure prophylaxis

PI: Protease inhibitor

Critical Appraisal Of The Literature

PubMed and the Cochrane Database of Systematic Reviews were searched for English-language articles related to the management of HIV/AIDS. Attention was focused on articles relevant to the emergency clinician, those published after 1996 (to coincide with the advent of HAART), and on articles that discussed the effects of chronic HIV infection and HAART adverse events. Search terms included HIV, AIDS, combination antiretroviral therapy, highly active antiretroviral therapy, and immune reconstitution inflammatory syndrome. Because of the large number of articles retrieved in these searches, the initial focus was on review articles with cross-referencing primary literature cited in the bibliographies. Relevant guidelines by the World Health Organization, the United States Department of Health and Human Services, and the American College of Emergency Physicians were also reviewed.

Now, nearly 20 years after the advent of HAART, considerable literature exists on the subject of HIV both in terms of the OIs patients experience and the chronic effects of longstanding illness and treatment. This literature provides strong evidence to support the practice recommendations made in this article.

Tables and Figures

Table 1. Major Adverse Effects Of Antiretroviral Medications


Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study are included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

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  3. Lima VD, Hogg RS, Harrigan PR, et al. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS. 2007;21(6):685-692. (Prospective; 2000 patients)
  4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Accessed August 5, 2015. (Government report)
  5. Rodger A, Bruun T, Cambiano V, et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER Study. Paper presented at: 21st Conference on Retroviruses and Opportunistic Infections, Abstract 153LB. March 3-6, 2014. (Prospective; 30,000 cases)
  6. * Palella FJ Jr, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43(1):27-34. (Prospective; 7000 patients)
  7. Hall HI, An Q, Tang T, et al. Prevalence of diagnosed and undiagnosed HIV infection – United States, 2008-2012. MMWR. 2015;64(24):657-662. (CDC report)
  8. * Mohareb AM, Rothman RE, Hsieh YH. Emergency department (ED) utilization by HIV-infected ED patients in the United States in 2009 and 2010 - a national estimation. HIV Med. 2013;14(10):605-613. (Observational; 1.1 milliion patients)
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  10. Napoli AM, Fischer CM, Pines JM, et al. Absolute lymphocyte count in the emergency department predicts a low CD4 count in admitted HIV-positive patients. Acad Emerg Med. 2011;18(5):565. (Retrospective; 866 patients)
  11. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337(11):725- 733. (Prospective randomized controlled; 1056 patients)
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  21. Stern JO, Robinson PA, Love J, et al. A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients. J Acquir Immune Defic Syndr. 2003;34 Suppl 1:S21-S33. (Prospective; 3000 patients)
  22. Fantry LE. Protease inhibitor-associated diabetes mellitus: a potential cause of morbidity and mortality. J Acquir Immune Defic Syndr. 2003;32(3):243-244. (Editorial)
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  27. Friis-Moller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356(17):1723-1735. (Prospective observational; 23,437 patients)
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  30. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):243-250. (Retrospective; 14,000 patients)
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Publication Information

David L. Gutteridge, MD, MPH; Daniel J. Egan, MD

Publication Date

February 1, 2016

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