HIV and diarrhea in the era of HAART: 1998 New York State hospitalizations

HIV and diarrhea in the era of HAART: 1998 New York State hospitalizations Joyce K. Anastasi, PhD, RN, FAAN, LAc Bernadette Capili, MS, CS, NP New York, New York

Background: This study reflects an attempt to identify the causes of diarrheal illness in hospitalized HIV patients in light of therapeutic advancements in HIV management. Methods: The study identifies the various etiologies associated with diarrhea among HIV patients hospitalized in New York State in 1998. Data for this study were extracted from the New York State Department of Health Statewide Planning and Research Cooperative System. Pathogens recognized to cause diarrhea in persons with HIV and general codes identifying diarrhea were examined by using the principal and all secondary diagnoses based on the International Classification of Diseases 9th Revision Clinical Modification codes. Results: Based on the Statewide Planning and Research Cooperative System data set, more than 15,000 patients with HIV were hospitalized in 1998. Among the HIV patients hospitalized, 2.8% were admitted with a diarrheal diagnosis. The following diagnoses occurred the most frequently among HIV patients hospitalized with a diarrheal illness: Clostridium difficile (51.3%), other protozoal diseases (18.1%), and other organisms, not elsewhere specified (11.7%). Conclusions: In the era of highly active antiretroviral therapy, diarrhea is still an occurring symptom in HIV patients. Despite the relatively small percentage of hospitalizations attributed to diarrhea, clinicians must remember that even “mild” to “moderate” diarrhea can have a debilitating impact among persons with the symptom. (AJIC Am J Infect Control 2000;28:262-6)

Diarrhea is a symptom commonly experienced among persons with HIV1 and generally associated with the underlying immunodeficiency.2 Diarrhea has been estimated to occur in 30% to 50% of European and North American persons infected with HIV.3 Diarrhea in persons with advanced disease is usually chronic (2 or more daily loose or watery stools for at least 30 days)4 and associated with significant morbidity, weight loss, and severe malnutrition.5 The pathogenesis of chronic diarrhea in HIV is complex and associated with multifactorial etiologies. Multiple parasites, pathogenic bacteria, and viruses have been isolated from the stools of approximately 75% to 80% of persons with AIDS2 and as many as 10% have multiple concomitant organisms.5 Although less common, chronic diarrhea has also been attributed to Kaposi’s sarcoma and B-cell lymphoma, which are opportunistic neoplasms affecting the gastrointestinal tract.1 In addition, side effects of medications and HIV enteropathy (a diagnosis of

From the Center for AIDS Research, Columbia University School of Nursing. Reprint requests: Dr Joyce K. Anastasi, Columbia University School of Nursing, 617 W 168th St, New York, NY 10032. Copyright © 2000 by the Association for Professionals in Infection Control and Epidemiology, Inc. 0196-6553/2000/$12.00 + 0 doi:10.1067/mic.2000.107585

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exclusion when enteric pathogens cannot be isolated) are listed as likely causes as well. EFFECTS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON DIARRHEA In the era of highly active antiretroviral therapy (HAART), the use of potent antiretrovirals has shown improvement in chronic diarrhea by clearing protozoan oocysts/spores from stool, reducing stool frequency, improving stool consistency and leading to weight gain.6-8 In the past, the treatment for pathogen-specific etiologies had only been minimally effective and palliative at best.2 Today, the use of HAART has allowed degrees of viral suppression with marked increases in CD4+ lymphocyte counts and a reduction in disease progression and mortality among persons with HIV.7 Thus HIV is now viewed as a chronic illness versus a life-threatening one. The most likely mechanism for this response is immune reconstitution through the use of HAART. Immune reconstitution has been described as the “return of pathogen- and HIV-specific lymphoproliferative responses and gradual increase in naïve CD4 cells.”9 Reversal of clinical signs and symptoms of opportunistic infections has been attributed to HAART.7 However, HAART has also been associated with inducing diarrhea in persons with HIV. Ten of sixteen currently approved antiretroviral medications have diarrhea listed as adverse side effects.10 The etiology and occurrence of chronic diarrhea in persons with HIV can be expected to dramatically change in the era of HAART.2 It is speculated that chronic diarrhea

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will increasingly result from antiretroviral side effects instead of enteric pathogens. The aim of this retrospective study was to describe the current state of diarrheal diagnoses among patients with HIV hospitalized in the state of New York. With the current advances in therapeutic regimens for persons with HIV, the authors were interested in investigating the causes and the incidence of diarrhea among hospitalized patients with HIV in 1998. For this study, enteric pathogens and diagnoses related to diarrhea were examined for more than 15,000 patients with HIV hospitalized in 1998 in New York State. In addition, age, sex, length of stay, Medicaid status, and discharge status after hospitalization were analyzed. DATA AND METHODS Data for this study were extracted from 1.3 million inpatient discharges from acute care hospitals in the state of New York for 1998. This study used data from the New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS). The collection of data for SPARCS was implemented in 1979 as part of a legislative mandate of the public health law.11 Each discharge abstract supplies patient demographic characteristics (ie, age, sex, and race), primary and secondary payment source, disposition at discharge (ie, home, hospice, or died), as many as 14 diagnosis and procedure codes, respectively, and measures of resource use (ie, length of stay and total charges) associated with hospitalization. The Discharge Data Abstract (DDA) collected by SPARCS is based on the Uniform Hospital Discharge Data Set developed by the National Committee on Vital and Health Statistics.11 To protect patient confidentiality, patient names are omitted from the SPARCS data set. SPARCS focuses on the incidence of diseases or conditions requiring hospitalization, rather than individual patients. Therefore, data obtained from SPARCS can only ascertain the number of hospitalizations for a specific disease and not the number of persons treated. All DDA received by SPARCS is screened for invalid and inconsistent entries. DDAs are also evaluated for duplicate entries. Study population The final sample used for the analysis consisted of 15,648 discharges. This was the result of abstracting the SPARCS data set for all discharges denoting the code for HIV (042), based on the International Classification of Diseases 9th Revision Clinical Modification (ICD-9-CM) codes. Dependent variables For this study, pathogens recognized to cause diarrhea in persons with HIV and general codes identifying

diarrhea were examined by using the principal and all secondary diagnoses. Pathogens that are widely recognized as organisms that can induce diarrhea were selected to evaluate the incidence among hospitalized patients with HIV. The following diagnostic codes were used to abstract the selected pathogens: • Giardia (0071) • Coccidiosis (Isosporiasis) (0072) • Clostridium difficile (pseudomembranous colitis) (00845) • Salmonella gastroenteritis (0030) • shigellosis (004) • Campylobacter (00843) In addition, 3 categories that cover a broad scope of diarrheal diagnoses were included. These codes encompass diarrheal diagnoses ranging from protozoal infections to noninfectious gastroenteritis. The codes were important to include because major pathogens and etiologies associated with chronic diarrhea were not found in other ICD-9-CM codes. For example, protozoal pathogens such as Cryptosporidium parvum12 and Microsporidia4 were not found as separate headings under the ICD-9-CM codes. In addition, cytomegalovirus, the most common viral pathogen identified with chronic diarrhea, did not have a separate category under the ICD-9-CM codes.5 Therefore, viral etiologies had to be covered under ICD-9-CM code 0088 (other organisms, not elsewhere classified [viral: enteritis and gastroenteritis]). Likewise, intestinal malabsorption and HIV enteropathy were not covered under separate headings. Malabsorption and HIV enteropathy can physiologically affect the gastrointestinal tract by altering ileal function and fat absorption, resulting in chronic diarrhea.3 The following ICD9-CM codes were used as proxy measures to capture the etiologies described previously: • Other protozoal intestinal diseases (007) • Other organisms, not elsewhere classified (viral: enteritis and gastroenteritis) (0088) • Ill-defined intestinal infections (diarrhea after gastrointestinal surgery, intestinal malabsorption, ischemic enteritis, other noninfectious gastroenteritis and colitis, regional enteritis, and ulcerative colitis) (009) Independent variables Patient demographics that were examined included sex, race, age, and payment source. Length of stay (LOS) greater than 5 days was also evaluated. In addition, patient disposition/status after hospitalization was assessed. This section was stratified into 5 categories: transferred home, transferred to home with home care services, transferred to an intermediate care facility, transferred to a hospice, or died. The categories

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Table 1. SPARCS inpatient 1998 data set: Profile of patients with HIV (N = 15,648) Variable

Age Men Medicaid LOS Died Home Transferred intermediate care facility Transferred with home care services Hospice

Mean

Standard deviation

40.5 y 63.7% 65.9% 11.3 days 6.2% 68.9% 0.30%

10.091 0.481 0.474 29.746 0.240 0.462 0.054

5.1%

0.221

0.03%

0.015

for LOS and disposition status were chosen because the average LOS for persons with chronic diarrhea and HIV has been cited as 30 days with numerous rehospitalizations during the course of a year.13 Hence, it was important to stratify these variables to assess for changes. Statistical analysis A univariate analysis on the entire discharge sample was conducted among all variables, dependent and independent, to determine the mean and standard deviation of each variable. Logistic regressions were used to analyze each diagnostic group as an outcome (ie, Giardia, Coccidiosis, C difficile, etc). SAS 6.12 (SAS Institute, Cary, NC) was used to analyze this data set. RESULTS Univariate analysis In 1998, 2.8% of the HIV hospital admissions in acute care New York State hospitals were the result of an enteric pathogen or other diarrheal illness. The mean age for these patients was 40.5 years. More than half of the patients admitted were men, and 65.9% were receiving Medicaid. The average LOS was 11.3 days. After hospitalization, 68.9% went home, 5% required home care services, and less than 1% were transferred to an intermediate care facility. In addition, 0.03% were transferred for hospice care and 6.12% died during their hospitalization (Table 1). From the ICD-9-CM codes associated with diarrheal illness in HIV, C difficile and other protozoal disease had the highest rates of occurrence at 51.3% and 18.1%, respectively. No observations were obtained from the Campylobacter code (Table 2). Logistic regression Logistic regressions that used Giardia, Salmonella, and shigellosis as the outcome variables found that

age, sex, race, Medicaid status, LOS, and disposition after hospitalization were not significant predictors for acquiring Giardia, Salmonella, or shigella among patients with HIV. However, persons infected with Coccidiosis (Isosporiasis) revealed that persons older than 50 years of age were more likely to be infected with this pathogen in comparison with younger HIV patients hospitalized (odds ratio [OR] 9.897, P < .01). In addition, men are less likely to be infected with this pathogen in comparison with women (OR = 0.256, P < .05), and whites are 4.5 times more likely to be infected with Coccidiosis (OR = 4.65, P < .05). Logistic regressions for C difficile revealed that HIV patients younger than 50 years were more likely to be infected with C difficile in comparison with persons older than 50 years (OR = 0.40, P < .001). In addition, HIV patients who use Medicaid were less likely to be infected with this organism (OR = 0.70, P < .05) in comparison with persons without Medicaid. Furthermore, patients with this pathogen were 4 times more likely to have been in the hospital for more than 5 days (OR = 4.1, P < .001) and were more likely to be discharged with home care services (OR = 1.9, P < .05) in comparison with persons free of this pathogen. HIV patients diagnosed with an ill-defined intestinal infection and HIV were 2 times more likely to stay in the hospital for more than 5 days (OR = 2.2, P < .05) than were persons who did not have an ill-defined intestinal infection. Those diagnosed with a protozoal infection were twice as likely to stay in the hospital for more than 5 days (OR = 2.1, P < .01) and three times more likely to require home care services after discharge (OR = 3.6, P < .001) in comparison with HIV patients without a protozoal infection. Finally, HIV patients diagnosed as having viral enteritis or viral gastroenteritis were 65% less likely to stay in the hospital for more than 5 days in comparison with persons without these diagnoses (Table 3). DISCUSSION This study reflects an attempt to identify the causes of diarrheal illness in light of therapeutic advances in HIV management. It was not surprising that less than 3% (2.8%) of the hospitalizations for HIV in New York State were related to a diarrheal illness in 1998. However, despite the relatively small percentage of hospitalizations related to diarrhea, clinicians must remember that even “mild” to “moderate” diarrhea can have a debilitating impact among persons with the symptom.14 Conclusions regarding the current state of diarrheal illness among persons with HIV cannot be determined on the basis of this study. The sample was limited to New York State and only used one data set from SPARCS. Pre-HAART data sets from SPARCS will

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Table 2. SPARCS inpatient 1998 data set: ICD-9-CM codes associated with diarrhea (N = 437) Variable

Giardia Coccidiosis (Isosporiasis) C difficile (pseudomembranous colitis) Salmonella gastroenteritis Shigellosis Campylobacter Ill-defined intestinal infections* Other protozoal diseases (colitis, diarrhea, dysentery) Other organism, not elsewhere specified (viral: enteritis, gastroenteritis)

Frequency

Percentage

Mean (%)

Standard deviation

23 10 224 7 3 0 40 79 51

5.3 2.3 51.3 1.6 0.69 N/A 9.2 18.1 11.7

1.47 0.06 1.43 0.05 0.02 N/A 0.26 0.51 0.33

0.04 0.03 0.12 0.02 0.01 N/A 0.05 0.07 0.06

*Includes: diarrhea after gastrointestinal surgery, intestinal malabsorption, ischemic enteritis, other noninfectious gastroenteritis and colitis, regional enteritis, and ulcerative colitis.

Table 3. ICD-9-CM coding associated with HIV and diarrhea: Significance and OR based on logistic regressions

Salmonella

Shigellosis

Ill-defined intestinal infection

Other protozoal diseases

Other organism, NOS (n = 51)

Giardia

Coccidiosis

C difficile

Age >50 y

.966

.959

.187

.103

.977

.577

.0003, OR = 0.403 .297

.964

Men

.331

.939

.969

.443

.435

White

.226

.544

.433

.487

.683

.217

.123

Medicaid

.175

.001, OR = 9.89 .045, OR = 0.256 .018, OR = 4.65 .764

.693

.588

.934

Died

.991

.999

.794

.999

.024, OR = 2.23 .502

.008, OR = 0.534 .005, OR = 2.05 .544

.848

.899

.061, OR = 0.203 .498

.939

LOS >5 days

Home TICF THCS

.522 .993 .109

.952 .999 .946

.013, OR = 0.703 .0001, OR = 4.09 .002, OR = 2.12 .345 .994 .017

.325 .995 .625

.954 .999 .995

.328 .994 .997

.087 .995 .008, OR = 3.57

.0006, OR = 0.350 .450 .285 .994 .388

NOS, Not elsewhere specified; TICF, transferred intermediate care facility; THCS, transferred with home care services.

be needed to make a comparison and analyze patterns regarding diarrheal illness in this population. The LOS variable was the only category that revealed several significant findings across the various diarrheal diagnoses (4 out of 8). Intuitively, it is not surprising that persons diagnosed with C difficile are more likely to stay in the hospital for more than 5 days. The majority of HIV patients with C difficile have had a history of antibiotic therapy, as in the general population infected with this pathogen.3 Perhaps patients diagnosed with this organism are on multiple antibiotic combination therapies, hence sicker and more debilitated. Further evidence that may support this finding is the increased likelihood of home care services once discharged from the hospital. Similarly, HIV patients diagnosed with protozoal infections are generally sicker and known to have lower CD4+ counts,5 thus explaining this increased LOS.

For patients diagnosed with an ill-defined intestinal infection, it is also not surprising that LOS would be greater than 5 days. Persons diagnosed with an illdefined intestinal infection may have had to undergo numerous diagnostic procedures to identify the causative agent for the intestinal infection. However, in patients with a diagnosis of other organism, not elsewhere specified, the reason behind the LOS is difficult to explain. According to the results, this type of diagnosis has a greater likelihood of staying less than 5 days in the hospital. A limitation of use of discharge data abstracts for the HIV population is the lack of access to CD4+ and viral load measurements to more accurately ascertain disease status. In addition, the inability to abstract antiretroviral medications and pharmaceutical side effects within the SPARCS database also limited the capability to assess the effects of HAART on diarrhea among

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persons with HIV. However, despite the limitations, the use of discharge abstracts is useful to assess the incidence and patterns of disease. Future studies are needed to identify the prevalence and impact of medication-induced diarrhea among persons with HIV. The identification of the health care needs of persons experiencing medication-induced diarrhea can assist with the development of appropriate therapeutic strategies to alleviate the symptom and the measurement of patient outcomes. References 1. Anastasi JK, Sun V. Controlling diarrhea in the HIV patient. Am J Nurs 1996;96(8):35-41. 2. Kartalija M, Sande MA. Diarrhea and AIDS in the era of highly active antiretroviral therapy. Clin Infect Dis 1999;28:701-7. 3. Lu SS. Pathophysiology of HIV-associated diarrhea. Gastroenterol Clin North Am 1997;26,2:175-89. 4. Tetreault D, Chang E. Managing and treating AIDS-related diarrhea: solutions for a common problem. Adv Nurse Pract 1998; July:55-60. 5. Framm SR, Soave R. Agents of diarrhea. Med Clin North Am 1997;81:427-47. 6. Carr A, Marriott D, Field A, Vasak E, Cooper DA. Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998;351:256-61.

7. Foudraine NA, Weverling GJ, van Gool T, Roos MTL, de Wolf F, Koopmans PP, et al. Improvement of chronic diarrhea in patients with advanced HIV-1 infection during potent antiretroviral therapy. AIDS 1998;12:35-41. 8. Koch J, Maimares-Schmidt J, Baidoo L, Keiserman M, Kim L. HIV-associated diarrhea: the changing spectrum and diagnoses [abstract No. 60635]. In: Conference record of the 12th World AIDS Conference (Geneva). Geneva; 1998 available online: http:// www.abstracts-online.com/s...s/abstracts/aids/AIDS.cfm/95890286. 9. Carpenter CCJ, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, et al. Antiretroviral therapy in adults: updated recommendations of the international AIDS society-USA panel. JAMA 2000;283:381-90. 10. Gilbert DN, Moellering RC, Sande MA. The Sanford: guide to antimicrobial therapy. 29th ed. Hyde Park (VT): Antimicrobial Therapy, Inc; 1999. 11. Statewide Planning and Research Cooperative System. Annual report. Volume 1:1-7. New York State Department of Health; 1990. 12. Anastasi JK, Capili B. Cryptosporidium. Home Healthcare Nurse 1997;15:307-15. 13. Lubeck DP, Bennett CL, Mazonson PD, Fifer SK, Fries JF. Quality of life and health service use among HIV-infected patients with chronic diarrhea. J Acquir Immune Defic Syndr 1993;6:478-84. 14. Snijders F, de Boer JB, Steenbergen B, Schouten M, Danner SA, van Dam FS. Impact of diarrhoea and faecal incontinence on the daily life of HIV-infected patients. AIDS Care 1998;10:629-37.

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Papers Accepted for Presentation at the APIC 27th Annual Educational Conference and International Meeting Minneapolis, Minnesota, June 18-22, 2000