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Incidence and Risk Factors Associated with Pressure Ulcers among Patients with HIV Infection

Nicastri, Emanuele MD, PhD; Viale, Pierluigi MD; Lyder, Courtney H. ND, GNP, FAAN; Cristini, Francesco MD; Martini, Lorena RN; Preziosi, Gianni RN; Dodi, Ferdinando MD; Irato, Laura MD; Pan, Angelo MD; Petrosillo, Nicola MDfor Gruppo HIV ed Infezioni Ospedaliere

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Advances in Skin & Wound Care: June 2004 - Volume 17 - Issue 5 - p 226-231

Pressure ulcers (PrUs) are localized areas of tissue necrosis that develop when soft tissue is compressed between a bony prominence and an external surface for a prolonged period of time. 1 The incidence of PrUs in hospitals varies from 0.4% to 38%. 1 PrUs impose a burden on health care systems in terms of cost, skilled medical care, and patient suffering. 2 In hospitals, the cost to treat a PrU has been estimated at $5000 to $40,000 per patient per year, depending on ulcer stage and degree of intervention. 3–5 In addition, PrUs have been associated with increased morbidity and mortality. 6 Preventing PrUs in the hospital should be the goal of the entire health care team. 7

Regression models have been used to identify risk factors that may place hospitalized patients at risk for PrU development. These risk factors include impaired mobility, urinary and fecal incontinence, malnutrition, age, hypoalbuminemia, and extended lengths of stay. 7–9 Many of the risk factors associated with PrU development are found among patients infected with human immunodeficiency virus (HIV). These patients represent a population of immunocompromised patients who can experience neurologic defects and develop conditions associated with the occurrence of PrUs, such as prolonged immobilization, postural deficiencies, and urinary and fecal incontinence, particularly during the advanced stage of HIV infection. 10,11 Although patients with advanced HIV infection appear to be as vulnerable to PrU development as older immunocompetent adults, 12 data on the incidence and risk factors associated with PrUs among patients infected with HIV are limited. The aim of this study was to assess the incidence of and risk factors for PrU development in patients infected with HIV type 1 (HIV-1) during the advanced stage of infection.


From March 1998 to July 1999, consecutive patients with advanced HIV-1 infection were recruited from 16 acute care infectious disease units in Italy (9 from northern, 6 from central, and 1 from southern Italy). The study design was approved by an institutional review board of the coordinating center.

A physician and/or an infection control nurse from each unit was trained in data collection and PrU staging. Surveillance was initiated on admission, and data were collected in each center during the routine daily unit visit, by staff interviews, and by chart review.

Surveillance data collected at admission included demographic information, history of risk factors for HIV, CD4 cell count, white blood cell and neutrophil counts, stage of HIV infection, Karnofsky performance status (KPS), 13 and Severity Index for Adults with AIDS (SIAA). 12 The KPS and SIAA scores were assigned according to the patient’s clinical situation on hospital admission and 3-month follow-up period. HIV infection was staged according to the 1993 classification system from the Centers for Disease Control and Prevention (CDC) 14; only patients infected with HIV-1 with conditions in subcategories B3, C1, C2, and C3 of the CDC classification system were enrolled in the study. Data on antiretroviral treatment and use of steroids and trimethoprim-sulfamethoxazole (cotrimoxazole) administered 30 days before admission and/or during the stay were included.

Invasive devices—including central venous catheters (CVCs) and urinary catheters—have been related to the development of PrUs; therefore, their use in study participants was recorded. Data on the occurrence of bloodstream infections, systemic inflammatory response syndrome (SIRS) and septic syndromes, discharge diagnosis, and patient outcomes were also collected.

PrUs were staged according to the standard staging system developed in 1989 by the National Pressure Ulcer Advisory Panel (NPUAP). 1 This staging system defines PrUs based on ulcer depth as follows:

  • Stage I— erythema that does not resolve within 30 minutes of pressure relief
  • Stage II— partial-thickness skin loss that may involve the epidermis or dermis, which presents clinically as an abrasion, blister, or shallow crater
  • Stage III full-thickness skin loss that involves the subcutaneous tissue
  • Stage IV— full-thickness skin loss, but with involvement of muscle, bone, or supporting structures such as tendon or joint capsule.

Swab cultures and tissue biopsies were not performed on PrUs.

Taking into consideration the minimum amount of time needed for PrUs to develop, analysis was performed only for patients with a hospital stay longer than 3 days. 7 To analyze the effect of length of stay on the occurrence of PrUs, frequency of PrUs was calculated according to the number of days the patient spent in the hospital. For patients with PrUs, the hospital stay was calculated from admission to the occurrence of the first PrU.

Descriptive statistics were used to describe the sample: the chi-square test to compare categorical variables and the Student t test for continuous variables. Univariate analysis was performed to examine possible risk factors for PrUs by computing odds ratios (ORs); confidence intervals (CIs) on ORs were calculated using an exact method. A multiple logistic regression model provided adjusted estimates of ORs while accounting for all possible risk factors. Two software programs—the Epi Info Version 5.1 (USD, Inc, Stone Mountain, GA) and EGRET (Statistics and Epidemiology Research Corporation, Seattle, WA)—were used to perform all statistical analyses.


As of August 1999, a total of 1924 admissions were recorded for 1313 patients with HIV-1 infection. Of those, 109 admissions were for fewer than 4 days and were excluded from the analysis. The analysis focuses on the remaining 1815 admissions for 1258 patients.

More men were admitted with HIV-1 infection than women: Of the 1815 admissions, 1347 were men (74.2%), with a median age of 37 years (mean 36, range 21 to 79). The median length of hospital stay was 15 days (mean 23, range 4 to 407). The most common risk factor for HIV infection was intravenous drug use, accounting for 808 of 1705 admissions (47.4%); 522 of these admissions were among still-active drug users. The median CD4 cell count was 101 cells/microliter (mean 147, range 0 to 1111). The median HIV-ribonucleic acid (HIV RNA) copy number (cp) was 10,600 cp/mL (mean 176,799; range < 20 to 8,400,000). The median absolute number of white blood cells was 4515 cells/mL (mean 5284, range 200 to 39,830). The median neutrophil cell count was 2575 cells/mL (mean 3182, range 10 to 9590).

During the study period, 47 PrUs were detected. Of those, 44 were included in the analysis. Three PrUs were excluded because they were detected on admission; the purpose of the study was to determine PrU incidence during hospitalization.

Frequencies of 2.31 PrUs per 100 admissions and 3.33 PrUs per 100 patients were found. The median frequency per facility was 2.6 PrUs per 100 patients (range 0 to 14.29). The incidence rate was 1.06 PrUs per 1000 patient days (95% CI 0.74–1.38).

Twenty-seven PrUs occurred in men (61.3%), with a median age of 37 years (range 26 to 70). The main risk factor for HIV-1 infection among these patients was intravenous drug use in 30 patients (68.2%), of which 14 (31.8%) remained active drug users, followed by unprotected heterosexual intercourse (10 cases, 22.7%). Pressure ulcers were classified as 7 Stage I (15.9%), 24 Stage II (54.5%), 8 Stage III (18.2%), and 5 Stage IV (11.4%).

Among patients with PrUs, the results of blood work were as follows: median CD4 cell count, 26 cells/microliter (mean 97, range 1 to 536); median HIV RNA copy number, 35,679 cp/mL (mean 195,164; range < 20 to 1,500,000); median absolute number of white blood cells, 4845 cells/mL (mean 5671, range 700 to 21,920); median neutrophil cell count, 3590 cells/mL (mean 4006, range 287–11,590).

Twelve patients with PrUs (27.3%) had bacteremia. Five patients had a polymicrobial infection, with a mean isolation rate of 2 organisms per patient. In 6 of 12 patients with bacteremia, the source was soft tissue infection at the PrU site. In the other 6 patients, the source was a CVC infection. Twenty-eight patients with PrUs had SIRS (6 cases of sepsis, 2 cases of severe sepsis, and 4 cases of septic shock).

Univariate analysis showed that being female, CD4 cell count less than 100 cells/microliter, KPS less than 50, C and D classes of SIAA score, and length of stay longer than 2 weeks were significantly associated with the occurrence of a PrU (Table 1). When fitted in a multivariate logistic regression model, only being female, KPS less than 50, C and D classes of SIAA score, and length of stay longer than 2 weeks remained significantly associated with PrUs (Table 1).

Table 1
Table 1:

Organisms isolated from blood cultures of patients showed that Staphylococcus spp accounted for 45.8% and 33.5% of all isolates in patients with and without PrUs, respectively (x2 = 1.4, P = .09;Table 2). Mortality rates were 50% and 7.2% among patients with and without PrUs, respectively (x2= 103.6, P < .0001), with an attributable mortality rate of 42.8% (95% CI 28.4–59.8) and an OR of 12.96 (95% CI 6.99–24.22). In the 12-month follow-up period, clinical improvement or complete healing was reported in 30% of PrUs.

Table 2
Table 2:


The present study represents the first multicenter prospective report on the emergence of PrUs in persons with HIV-1 infection, a phenomenon that is a recognized occurrence in clinical practice. Neither cross-sectional nor longitudinal analysis has been carried out to study the incidence of and risk factors for PrUs specific for HIV-1 infection.

The frequency of 3.33 PrUs per 100 inpatients is comparable to the range of frequencies found in prospective studies of HIV-negative acute care inpatients (1% to 7%). 1,3,15 However, 70% of PrUs in 2 of these studies occurred in patients over age 65, an age group particularly susceptible to PrUs when hospitalized. 15,16 In the present study, the patient population was much younger, with a mean age of 38 years. Younger, HIV-infected patients with neurologic disorders and low functional status (evidenced by a low Karnofsky score) seem to share the same PrU risk rates as younger HIV-negative inpatients with underlying neurologic disorders, such as cerebral palsy, multiple sclerosis, and spinal cord lesions. 17,18

Since 1996, morbidity and mortality rates among patients infected with HIV-1 have decreased sharply due to the advent of highly active antiretroviral therapy (HAART). 19 However, patients infected with HIV-1 still experience a marked reduction in nutritional status and a significant depression of the host immune response to HIV and other opportunistic organisms. This is likely related to an insufficient immune recovery and/or the emergence of drug-resistant HIV-1 strains. 20,21 All of these factors are likely involved in the emergence of PrUs in patients infected with HIV.

In the multivariate analysis of the present study, clinical parameters such as KPS and SIAA score appear to be related to the emergence of a PrU. SIAA is assigned according to the patient’s clinical situation during the 3-month follow-up period and appears to be extremely useful in predicting the intermediate or long-term clinical prognosis of patients, with or without PrUs. The surrogate markers of HIV clinical progression, such as HIV-1 viral load and CD4 cell count, were not associated with the presence of a PrU. Although patients with PrUs had a higher HIV viral load and lower CD4 count than patients without PrUs, it is likely that PrU risk depended more on the subjects’ functional and general health conditions than on their immunovirologic status.

The length of hospitalization was independently associated with PrUs. Longer hospital stays most likely indicate patients with more severe conditions that may keep them bedridden, including comorbidities such as hepatitis B and C and human herpesvirus type 8 infections. This finding has been evidenced in several reports conducted in HIV-negative inpatients, 1,15,16 where linear correlation models showed that the fold-increase of developing a PrU was directly related to the length of hospitalization.

Another finding from the present study was the association between PrUs and the female gender among hospitalized patients infected with HIV-1. In studies conducted with HIV-negative inpatients, gender was not univocally associated with PrUs. 22,23 However, in 2 studies, 24,25 women had a higher incidence of PrUs compared with men. It is unclear whether these findings are due to gender differences or epidemiologic differences (ie, having more women in both studies).

Grinspoon et al 26 demonstrated that women infected with HIV lose significant lean body and muscle mass in the late stages of AIDS wasting. In contrast to men, women exhibit a progressive and disproportionate decrease in body fat relative to lean body mass at all stages of AIDS wasting, consistent with gender-specific effects in body composition in AIDS wasting. In addition, Grinspoon et al 26 demonstrated that androgen deficiency is common in women with AIDS wasting and may contribute to decreased muscle mass in this population.

Some biologic skin changes, such as dehydration or other manifestations related to malnutrition, could occur in the skin of women more susceptible to skin breakdown than men. In the present study, women who developed PrUs had more frequent clinical presentations related to malnourishment (mainly AIDS wasting syndrome) than men with PrUs (17.7% vs 3.7%, respectively; P = .3). However, other uninvestigated social, physiologic, and pathologic risk factors for PrUs could play a role in the more frequent risk of PrU development among women. In particular, local skin conditions due to nutritional status, hormone levels, and urinary and fecal incontinence could play a role. Further studies are needed to distinguish the association of being female with the development of PrUs.

The role of infection at the PrU site remains unclear as a determinant of bacteremia and sepsis 2,27 because of the difficulty in distinguishing colonization from infection. In the present study, however, more than 25% of patients with PrUs had bacteremia and a septic syndrome, and the likely source of infection was the PrU site in one-half of them. This is consistent with findings by Bryan et al, 28 who studied 104 episodes of bacteremia in 102 patients with infected PrUs and noted that the ulcers were the probable source of bacteremia in approximately one-half of the episodes. The overall mortality rate in their study was 55%, with 51% of deaths attributable to infection. 28 Similarly, in the present study, the mortality rate among patients who were infected with HIV-1 and who had a PrU was 50%, with a mortality rate of 42.8% attributable to the PrU. Furthermore, in the present study, only one-third of patients who were infected with HIV-1 and who had a PrU improved clinically during the follow-up period; the remaining subjects had very poor clinical outcomes, with a high mortality rate.

Among the organisms isolated in blood culture from HIV-infected patients with PrUs, Gram-positive organisms—particularly S aureus and coagulase negative S epidermidis—were the pathogens most commonly reported to cause bloodstream infection. As expected, the risk of infection appeared to be greater in patients with a CVC device. 12,28,29 A likely explanation for the high frequency of these organisms is the high rate of S aureus carriage among patients infected with HIV, with frequencies ranging from 34.0% to 52.9%. 30–33 Recent data indicate that more than 80% of the S aureus bacteremia is secondary to skin/mucus colonization. 34

In the present study, 30% of PrUs in patients with HIV-1 infection either had improved or completely healed. This suggests that with appropriate treatment, a PrU can improve or heal independent of the patient’s compromised immune system. In addition, functional status was a better predictor of PrU development than immune status. This suggest that opportunities exist for using preventive interventions, such as PrU prediction scales, repositioning, support surfaces, and correcting nutritional deficits, to prevent PrUs in a vulnerable population.

The present study has several inherent limitations. First, a scale for predicting the risk of developing a PrU, such as the Braden, Waterlow, or Norton scales, was not used. 35 However, the KPS and SIAA severity scores were strongly associated with the occurrence of PrUs and can be considered as surrogate markers of functional status.

Clinicians should be aware that functional status and clinical conditions that prolong the hospital stay of patients infected with HIV-1 greatly influence PrUs development. Therefore, aggressive preventive strategies and early diagnosis of this serious, fastidious, and potentially long-lasting complication should be implemented. The identification of the clinical, virologic, and immunologic risk factors for PrUs in these patients may provide better insight into the therapeutic strategies targeted to reduce the dramatic impact of this nosocomial noninfectious complication.


The authors thank Zana Mariano for assistance with text revisions. This study was supported by grants from the Research Program, Ministry of Health, and from the National Research Program on AIDS, National Institute of Health, Italy.


1. Pressure ulcers prevalence, cost and risk assessment: consensus development conference statement—The National Pressure Ulcer Advisory Panel. Decubitus 1989;2(2):24–8.
2. Kanj LF, Wilking SV, Phillips TJ. Pressure ulcers. J Am Acad Dermatol 1998;38:517–36.
3. Allman RM, Laprade CA, Noel LB, et al. Pressure sores among hospitalized patients. Ann Intern Med 1986;105:337–42
4. Alterescu V. The financial costs of inpatient pressure ulcers to an acute care facility. Decubitus 1989;2(3):14–23
5. Kerstein M, Gemmen E, van Rijswijk L, et al. Cost and cost effectiveness of venous and pressure ulcer protocols of care. Disease Management Health Outcomes 2001;9:651–63.
6. Smith DM. Pressure ulcers in the nursing home. Ann Intern Med 1995 123:433–42.
7. Lyder CH, Preston J, Grady JN, et al. Quality of care for hospitalized Medicare patients at risk for pressure ulcers. Arch Intern Med 2001;161:1549–54.
8. Allman RM, Goode PS, Patrick MM, Burst N, Bartolucci AA. Pressure ulcer risk factors among hospitalized patients with activity limitation. JAMA 1995;273:865–70.
9. Brandeis GH, Morris JN, Nash DJ, Lipsitz LA. The epidemiology and natural history of pressure ulcers in elderly nursing home residents. JAMA 1990;264:2905–9.
10. 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.
11. Meehan RA, Brush JA. An overview of AIDS dementia complex. Am J Alzheimers Dis Other Demen 2001;16:225–9.
12. Petrosillo N, Pugliese G, Girardi E, et al. Nosocomial infections in HIV infected patients. Gruppo HIV e Infezioni Ospedaliere. AIDS 1999;13:599–605.
13. Yates JW, Chalmer B, McKegney FP. Evaluation of patients with advanced cancer using the Karnofsky performance status. Cancer 1980;45:2220–4.
14. CDC. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992;41:1–19.
15. Whittington K, Patrick M, Roberts JL. A national study of pressure ulcer prevalence and incidence in acute care hospitals. J Wound Ostomy Continence Nurs 2000;27:209–15.
16. Young JB, Dobrzanski S. Pressure sores. Epidemiology and current management concepts. Drugs Aging 1992;2:42–57.
17. Bliss MR. Pressure injuries: causes and prevention. Hosp Med 1998;59:841–4.
18. Reuler JB, Cooney TJ. The pressure sore: pathophysiology and principles of management. Ann Intern Med 1981;94:661–6.
19. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853–60.
20. Perrin L, Telenti A. HIV treatment failure: testing for HIV resistance in clinical practice. Science 1998;280:1871–3.
21. Descamps D, Flandre P, Calvez V, et al. Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilege (Agence Nationale de Recherches sur le SIDA 072) Study Team. JAMA 2000;283:205–11.
22. Bergquist S, Frantz R. Pressure ulcers in community-based older adults receiving home health care. Prevalence, incidence, and associated risk factors. Adv Wound Care 1999;12:339–51.
23. Papanikolaou P, Clark M, Lyne PA. Improving the accuracy of pressure ulcer risk calculators: some preliminary evidence. Int J Nurs Stud 2002;39:187–94.
24. Heinemann A, Lockemann U, Matschke J, Tsokos M, Puschel K. Decubitus ulcer in the terminal phase: epidemiologic, medicolegal and ethical aspects. [German] Dtsch Med Wochenschr 2000;125:45–51.
25. Lyder CH, Yu C, Emerling J, et al. The Braden Scale for pressure ulcer risk: evaluating the predictive validity in Black and Latino/Hispanic elders. Appl Nurs Res 1999;12:60–8.
26. Grinspoon S, Corcoran C, Miller K, et al. Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting. J Clin Endocrinol Metab 1997;82:1332–7.
27. Livesley NJ, Chow AW. Infected pressure ulcers in elderly individuals. Clin Infect Dis 2002;35:1390–6.
28. Bryan CS, Dew CE, Reynolds KL. Bacteremia associated with decubitus ulcers. Arch Intern Med 1983;143:2093–5.
29. Frank U, Daschner FD, Schulgen G, Mills J. Incidence and epidemiology of nosocomial infections in patients infected with human immunodeficiency virus. Clin Infect Dis 1997;25:318–20.
30. Omenaca C, Turett G, Yarrish R, et al. Bacteremia in HIV-infected patients: short-term predictors of mortality. J Acquir Immune Defic Syndr 1999;22:155–60.
31. Petrosillo N, Viale P, Nicastri E, et al. Nosocomial bloodstream infections among human immunodeficiency virus-infected patients: incidence and risk factors. Clin Infect Dis 2002;34:677–85.
32. Skiest DJ, Grant P, Keiser P. Nontunneled central venous catheters in patients with AIDS are associated with a low infection rate. J Acquir Immune Defic Syndr Hum Retrovirol 1998;17:220–6.
33. Dega H, Eliaszewicz M, Gisselbrecht M, et al. Infections associated with totally implantable venous access devices (TIVAD) in human immunodeficiency virus-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 1996;13:146–54.
34. von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 2001;344:11–6.
35. Gould D, Goldstone L, Gammon J, Kelly D, Maidwell A. Establishing the validity of pressure ulcer risk assessment scales: a novel approach using illustrated patient scenarios.
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