Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage

doi:10.4236/wja.2012.23031

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World Journal of AIDS, 2012, 2, 237-244

doi:10.4236/wja.2012.23031 Published Online September 2012 (http://www.SciRP.org/journal/wja)

237

Challenges in Managing Hospitalized HIV Infected

Persons with Low Absolute CD4 and Preserved CD4

Percentage

Steven M. Bobula, Carl J. Fichtenbaum

Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, USA.

Email: [email protected]

Received May 18th, 2012; revised June 21st, 2012; accepted July 8th, 2012

ABSTRACT

Background: HIV infected persons are at risk for opportunistic illnesses based upon severity of immune deficiency.

Management is generally based upon the most recent absolute CD4 count. We hypothesized there is a group of patients

with a low absolute CD4 count and preserved CD4 percentage that are at low risk of AIDS-related opportunistic ill-

nesses (OI). Methods: A retrospective review of medical records in HIV-infected persons hospitalized from 2004-2006.

Individuals without CD4 counts available within 180 days of admission and during hospitalization were excluded. Pa-

tients with a decrease in the absolute CD4 count during hospitalization and stable CD4 percentage were compared to the

rest of the cohort. Appropriate management was defined using DHHS guidelines for the prevention and treatment of

opportunistic illnesses in HIV infection. Results: 464 patients had 978 hospitalizations. In 221 hospitalizations (N =

161 patients) inpatient and outpatient CD4 counts were available. In 35 hospitalizations (N = 25 patients) the absolute

CD4 count declined with stable CD4 percent (cases). Cases had an average decline in CD4 of –197 cells/mm3 compared

to –5 cells/mm3 in the comparator group. 30% of comparators had AIDS defining OI’s compared to none in the case

group (p = 0.01). Management outside of DHHS guidelines was more common in cases compared to the comparator

group (49% vs 30%, p = 0.048). The median length of stay was prolonged in cases with management outside guidelines

compared to appropriately managed persons in the comparator group (7 days vs 3.5 days, p = 0.03). Conclusion: In

persons on potent antiretroviral therapy, abrupt declines in absolute CD4 counts without an accompanying change in

CD4 percentage are associated with a low risk of AIDS related opportunistic infection, a higher rate of in-patient man-

agement outside DHHS guidelines, and a more prolonged length of stay.

Keywords: HIV; CD4 Count; Risk Stratification; Acute Illness; Opportunistic Infections

1. Introduction

T-lymphocytes have been used to assess risk for the de-

velopment of Acquired Immune Deficiency Syndrome

(AIDS) related opportunistic illnesses (OIs) for 3 decades

[1,2]. The risk for developing specific infections is typi-

cally defined by the absolute number of circulating CD4

positive lymphocytes [3]. Although risk stratification

may be estimated using the percentage of circulating

CD4 lymphocytes, this is uncommon in clinical practice.

Most clinicians utilize the most recent absolute CD4

count to estimate the severity of HIV associated immune

deficiency.

In persons hospitalized with HIV, recent CD4 counts

and HIV RNA levels may not always be available. Con-

sequently, individuals hospitalized with HIV often have

CD4 counts and HIV RNA levels obtained within the

first day or two to risk stratify the likelihood of various

OIs.

We hypothesized that some HIV infected adults hos-

pitalized for acute conditions and illnesses are incorrectly

risk stratified and managed based upon acutely measured

lower absolute CD4 counts. This decline in the number

of circulating lymphocytes occurs during stress reactions

associated with acute disease states. The accompanying

CD4 percentage is likely to be preserved at near pre-

hospitalization levels enabling the clinician to distinguish

between those with and without a biologically important

decline. These patients are characterized by ongoing use

of antiretroviral therapy with prior HIV viral loads near

the limit of detection and good self-reported recent ad-

herence to treatment. Therefore, we evaluated the impact

of measuring inpatient CD4 counts on influencing the

diagnostic approach, empiric management, outcome and

length of stay for HIV infected persons who were hospi-

talized.

Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage

238

2. Methods

2.1. Setting

An academic, 700-bed, urban, public hospital located in

Cincinnati, Ohio. The study was approved by the institu-

tional review board at the University of Cincinnati.

2.2. Population and Study Design

A retrospective review of the medical records of all

HIV-infected persons admitted to University Hospital

from 2004-2006. Participants were excluded from further

analysis if they were less than eighteen years of age, did

not have HIV infection documented by positive ELISA

and confirmed by Western Blot, were not being pre-

scribed antiretroviral therapy for at least 4 months, or did

not have CD4 counts drawn during their inpatient stay

and within 180 days prior to admission.

Patients were divided into case and comparator groups

based the stability or instability of their inpatient and

outpatient CD4 counts and percentages. Cases were arbi-

trarily classified if there was a >20% decline in absolute

CD4 count with a <20% decline in absolute CD4 percent

compared to prior outpatient values obtained within 180

days of hospitalization. For example, a patient hospital-

ized where the outpatient and inpatient absolute CD4

counts and percentages were 372/19% and 180/18%,

respectively. We chose this level of change based upon a

priori clinical rationale that there is significant variability

in the CD4 assays and that a minimum of at least 20%

change was likely to be biologically more important.

Patients not meeting this definition were used as a com-

parator group (Figure 1).

2.3. Data Collection

Using standardized data collection forms, the medical

records were abstracted for demographic data, admission

and discharge diagnoses; specialty of health care provid-

ers involved in the patient’s care; use of antiretroviral

therapy; length of hospitalization; antibiotic utilization,

use of OI prophylaxis and treatment; use of adjunctive

corticosteroids; procedures performed; microbiologic

studies; laboratory tests; complications from medications

Hospitalizations

(N = 978)

Hospitalizations

(N = 221)

757 Hospitalizations Excluded

454: No inpatient CD4 count

236: No outpatient CD4 count

60: No CD4 counts available

7: < 24 hours of hospitalization

Comparator Group

(N = 186 hospitalizations)

To be included may have any one of the following:

Both absolute and percentage CD4 ↓ > 20%

No change absolute or percent CD4

↑ Absolute CD4 > 20% with stable CD4 percentage

Both absolute and percentage CD4 ↑ > 20%

Case Group

(N = 35 hospitalizations)

↓ In absolute CD4 count > 20% with < 20% change in

CD4 percentage compared to pre-admission values.

Yes Yes Yes Yes No

Figure 1. Consort diagr am of study population. A descr iption of the study population evaluated over 3 year s of the study. The

case group was defined by those admitted with a >20% decline in absolute CD4 count without a significant change in CD4

percentage. The comparator group was defined by those with either no change in CD4 or a significant change > 20% in both

absolute and percentage of CD4 cells.

Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage 239

or procedures; and hospital outcomes. All charts were

reviewed by both authors. Management within or outside

standard guidelines were assigned regardless of whether

the subject was later classified as a case or comparator.

When there was disagreement between the authors, a

consensus method was used to resolve differences.

2.4. Definitions

Appropriateness of management was determined by

comparing the patients’ management relative to current

Department of Health and Human Services (DHHS) and

other available guidelines on the treatment and preven-

tion of OIs in persons infected with HIV [3-6]. Risk

stratification to determine appropriateness of care was

based upon the most recent outpatient CD4 count. If

there was more than one measurement within 180 days,

we used the one most proximate to hospitalization. We

assumed that if there was no documented interruption in

antiretroviral therapy, absolute CD4 counts would be

unlikely to decline significantly in the absence of inter-

current illness or laboratory error. An HIV specialist was

defined as a practitioner who routinely provides inpatient

and outpatient care to individuals infected with HIV.

2.5. Laboratory Methods

HIV plasma RNA levels (HIV viral load) were measured

using the Amplicor HIV-1 monitor test, version 1.5, in

the local affiliated laboratory. Lymphocyte subset quan-

tification, including CD4 counts, was obtained by flow

cytometry.

2.6. Statistical Analysis

The primary objective was to compare differences in

adherence to DHHS management guidelines between the

case and comparator groups. Secondary objectives in-

cluded use of unneeded prophylaxis and treatment for P.

jirovecii pneumonia and disseminated M. avium complex;

determining if the involvement of an HIV specialist in

the subject’s care led to a lower rate of deviation of

management from standard guidelines; determining if

there were differences in the occurrence of AIDS defin-

ing opportunistic infections; and evaluating the effect of

adherence to management guidelines on length of stay,

morbidity, and mortality; however, the study was not

powered to determine a difference in mortality.

The study was designed to prove an absolute 10% dif-

ference in deviation from management guidelines in

persons with an acute decline in absolute CD4 counts

obtained during their hospitalization. We estimated a

sample size of 120 hospitalizations was needed, assum-

ing that the rate of management deviation in the com-

parator population is approximately 19% (Power of 80%,

P < 0.05, two tailed). A P that was less than or equal to

0.05 was considered statistically significant.

All data was analyzed by using SAS 9.1.3 (SAS Insti-

tute, Cary, North Carolina). Chi squared testing was per-

formed to compare categorical variables. Nonparametric

methods were used to compare continuous variables.

Categorical variables are reported with number and per-

centage of total population. Median results with reported

minimum and maximum ranges were used to report most

continuous variables. For analysis of HIV viral loads, we

assigned arbitrary next value to those below the limit of

detection. For example, those with an HIV viral load <

50 copies/mL were assigned a value of 49 copies/mL for

statistical analysis.

3. Results

There were 978 hospitalizations of 464 unique patients

from 2004-2006. 221 hospitalizations had inpatient and

outpatient CD4 counts available. Of these, 35 hospitali-

zations (25 patients) had a decreased absolute CD4 count

(>20%) on admission without a significant decline in

CD4 percentage (<20%). The remaining 186 hospitaliza-

tions (136 patients) comprised the comparator group.

This included persons where the absolute CD4 count

remained stable or both the absolute CD4 and percentage

both declined or, increased. There were no statistically

significant differences between the groups with respect to

age, gender or race (Table 1). Comorbid conditions pre-

sent at the time of hospitalization were not significantly

different between the two groups. An HIV expert was

involved in the management of 49% of case hospitaliza-

tions and 45% of comparator hospitalizations (p = 0.71).

Three deaths occurred during the study, two in the

comparator group and one in the case group. In the com-

parator group, a 47-year-old man died with disseminated

Table 1. Study population demographics.

Case Group*

(N = 25)

Comparator

Group* (N = 136)

Median Age in Years

(Range) 44 (27, 65) 42 (21, 65)

Gender

Male 80% 80%

Female 20% 20%

Race

African American 48% 64%

Caucasian 48% 32%

Hispanic 4% 2%

Other/Not Identified - 2%

*Represents number of patients not hospitalizations.

Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage

240

T. gondii and M. avium disease. His outpatient and inpa-

tient absolute CD4 counts and percentages were <1 cells

per cu mm/0% and 9 cells per cu mm/7%, respectively,

and had an HIV viral load that was greater than 100,000

copies/mL despite self-reported adherence with highly

active antiretroviral therapy (HAART). The second

comparator group death involved a 39-year-old woman

who died from P. jirovecii pneumonia. Her outpatient

absolute CD4 count and percentage of 179 cells per cu

mm/17% had decreased to 26 cells per cu mm/8% on

admission. She had been intermittently adherent with

HAART and had an HIV viral load greater than 750,000

copies/mL. The case group death involved a 49-year-old

man with bacterial meningitis who presented with an

inpatient absolute CD4 count and percentage of 43 cells

per cu mm/13% (outpatient values of 242 cells per cu

mm/16%). He had been reportedly adherent with

HAART and had a HIV viral load of 16,800 copies/mL.

The only minor deviation from standard management

observed in these three patients involved failure to ad-

minister prophylaxis for M. avium complex in the second

comparator case.

Patients in the case group had higher CD4 counts and

percentages before (407 cells per cu mm/20% versus 101

cells per cu mm/18%, P < 0.0001), during (180 cells per

cu mm/18% versus 101 cells per cu mm/10% with P <

0.05), and after hospital admission (373 cells per cu

mm/19% versus 159 cells per cu mm/10% with P = 0.001)

than the comparator group. The case group was also noted

to have lower median pre-admission viral loads than the

comparator group (476 copies/mL compared to 31,724

copies/mL, P = 0.001). The acute decline in CD4 count

seen in the case group generally reversed when subjects

were retested as outpatients (Table 2) after discharge.

Table 2. CD4 Counts and HIV-1 RNA Levels.

Case Group (N = 35) Comparator Group

(N = 186) P-value

Absolute Median CD4 count in cell/mm3 (ranges)

Values between 6 - 12 months before admission 343 (39, 953) 138 (0, 920) 0.0002

Values within 6 months before admission 407 (118, 1,252) 101 (0, 1,531) <0.0001

Values during admission 180 (22, 777) 101 (0, 1738) 0.05

Change in absolute CD4 from pre-admissiona –197 (–484, –68) –5 (–575, 780) <0.0001

Absolute CD4 1 - 3 months after admission 333 (71, 1,128) 159 (0, 1,344) 0.001

Change in absolute CD4 after dischargeb 149(–294, 680) 24 (–202, 687) <0.0001

Median CD4 percentage (ranges)

Values between 6 - 12 months before admission 20 (7, 38) 10 (0, 50) <0.0001

Values within 6 months before admission 20 (11, 44) 8 (0, 50) <0.0001

Values during admission 18 (11, 40) 10 (0, 38) <0.0001

Change in percent CD4 from pre-admissiona –3 (–14, 8) 0 (–18, 19) <0.0001

Percent CD4 1 - 3 months after admission 19 (7, 43) 10 (0, 50) 0.0004

Change in percent CD4 after dischargeb 2 (–9, 15) 0 (–10, 37) 0.07

Median HIV-1 RNA in copies/mL (ranges)

Values between 6-12 months before admission 5580 (<50, >750,000) 20,400 (<50, >750,000) 0.51

Values within 6 months before admission 476 (<50, 269,000) 31,724 (<50, >750,000) 0.001

Values during admission 399 (<50, 365,000) 26,550 (<50, >750,000) 0.17

Values 1 - 3 months after discharge 745 (<50, >750,000) 2311 (<50, >750,000) 0.40

aDifference between values measured within 6 months of admission compared to those measured during admission. bDifference between values measured dur-

ing admission compared to those measured 1 - 3 months after discharge. Note: All ranges represent minimum and maximum values.

Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage 241

Patients that presented with a sudden decline in abso-

lute CD4 were more often diagnosed with febrile ill-

nesses as opposed to non-febrile illnesses (Ta b l e 3). Feb-

rile illnesses were noted in 71% of case group patients

compared to 49% of those in the comparator group (P =

0.01). Lobar pneumonias were the most common febrile

illness diagnosed in both groups, and were found more

frequently in cases than comparators (P = 0.0007). AIDS

defining OIs were common (30%) in the comparator

group but were not observed in the case group (P = 0.01).

There was a non-significant trend of more episodes of

bacteremia, sepsis, or urinary tract infections in the case

group (P = 0.09). Diagnoses in the remaining 29% of the

case group without febrile illness included multiple organ

system trauma, craniofacial injuries, and acute long bone

fractures. Case and comparator hospitalizations were

remarkably similar regarding severity of illness. Inten-

sive care unit management was required 20% of cases

and 11% of comparators (P = 0.13). Both groups had

median APACHE-II scores of 8 (P = 0.88).

Management outside standard guidelines was observed

in 49% of patients hospitalized with an abrupt decline in

absolute CD4 count without a significant change in CD4

percent (Case group). In contrast, 30% of patients in the

comparator group were managed outside standard guide-

lines (P = 0.048). HIV experts were involved in 41% of

case hospitalizations and 43% of comparator hospitaliza-

tions that were not managed per guidelines (P = 0.86).

The most common reasons for deviation from manage-

ment by guidelines were generally minor and included

administration of prophylaxis for P. jirovecii and M.

avium when they would not have been indicated. In sev-

eral instances management deviations included use of

laboratory studies and procedures (bronchoscopy or

lumbar puncture) that were not absolutely required (Ta-

ble 4). An example of a more significant deviation from

standard guideline management involved a 64-year-old

man with outpatient and inpatient absolute CD4 count

and CD4 percentage of 472 cells per cu mm/16% and

157 cells per cu mm/13%, respectively, admitted for

pneumonia (Case group). His HIV viral load prior to

admission was <50 copies/mL. A lobar infiltrate was

noted on the chest radiograph. According to the physi-

cian notes, the bronchoscopy was ordered to evaluate for

P. jirovecii specifically due to the absolute CD4 count

being less than 200 cells per cu mm. In this case, bacte-

rial pneumonia was retrospectively judged to be far more

likely. The absolute CD4 was <200 cells/cu mm because

of the relative lymphopenia due to a “left shift” with many

neutrophils circulating in a patient with a presumed bacte-

rial pneumonia. Another example of deviation from stan-

dard management occurred in a 48-year-old male with

outpatient and inpatient absolute CD4 count and CD4

percentage of 958/30% and 1738/29%, respectively that

was admitted for evaluation of seizure (Comparator group).

The patient did not have fever and outpatient HIV viral

load was <50 copies/mL. Review of the patient's chart

noted that the primary team responsible for his care noted

that he was HIV infected and specifically performed lum-

bar puncture to assess for a possible AIDS-defining OI.

Table 3. Diagnoses during hospitalizations.

Case Group (N = 35) Comparator Group (N = 186) P-value

Non-febrile illnesses 29% 51% 0.01

Febrile Illnessesa71% 49% 0.01

Pulmonaryb 46% 19% 0.0007

Bacteremia/Sepsis 17% 8% 0.09

Urinary Tract Infection 9% 3% 0.09

AIDS Defining OIc 0% 16% 0.01

Skin and Soft Tissued 3% 5% 0.53

Gastrointestinale 3% 2% 0.61

Immune Reconstitution Syndrome 0% 2% 0.38

Viral Syndrome 0% 1% 0.54

Fever of Unknown Origin 3% 3% 0.96

Other Miscellaneous Illnesses 9% 1% 0.01

aPatients may have had more than one febrile illness diagnosis during hospitalization. bPneumonia, COPD exacerbation. cP. jir ovecii pneumonia,

disseminated M. avium, disseminated cytomegalovirus, Cryptococcus meningitis, cerebral or disseminated Toxoplasma. dCellulitis, skin abscess.

eAcute gastroenteritis, C. difficile colitis.

Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage

242

Table 4. Descriptions of management outside standard guidelines.

Management outside guidelines Case group (N = 35)Comparator group (N = 186) P-value

Total 49% 30% 0.03

PCPa prophylaxis not indicated, given 26% 8% 0.001

PCPa prophylaxis indicated, not given 6% 5% 0.93

M. avium prophylaxis not indicated, given 3% 6% 0.41

M. avium prophylaxis indicated, not given 0% 13% 0.02

Multiple non-indicated laboratory testsb 17% 3% 0.001

Non-indicated procedurec 11% 3% 0.02

Miscellaneous events 3% 1% 0.18

Note: Some hospitalizations had multiple associations with management outside standard guidelines. aPneumocystis pneumo-

nia. bBlood fungal culture, Acid Fast Bacillus Blood Culture or serum Cryptococcal Antigen. cLumbar puncture or broncho-

scopy.

Patients that were managed outside standard guide-

lines based on absolute CD4 count had a median length

of stay of 5 days versus 4 days compared to those that

were managed per guidelines (P = 0.06). Case hospitali-

zations that were managed outside guidelines had a me-

dian length of stay of 7 days versus 3.5 days for those

managed within guidelines in the comparator group (P =

0.03) (Figure 2). There was no significant difference in

the length of stay between cases and comparator group

Figure 2. Length of Stay Comparison. On the left hand side

of chart is a comparison of appropriately managed hospi-

talizations to non-standard managed hospitalizations (re-

gardless of whether they were cases or comparators) dem-

onstrating a trend towards statistical significance (P = 0.06)

of increased length of stay in those with non-standard

management. On the right hand side of the chart is a com-

parison of appropriately managed hospitalizations in the

comparator group (*Comp.) versus those who were man-

aged in a non-standard fashion in the case group (cases)

that was statistically different with a longer length of stay in

the case group, P = 0.03.

patients (P = 0.52) who adhered to management guide-

lines or in those who did not adhere to management

guidelines (cases versus comparator patients, P = 0.15).

4. Discussion

We found that 49% of patients that presented with a

marked decline in absolute CD4 count associated with

preserved CD4 percentage during an acute illness were

managed outside recommended DHHS and other rele-

vant practice guidelines, compared with 30% of the

comparator group. The case group also had prompt re-

covery of CD4 counts post admission and generally had

lower pre-admission HIV-1 RNA levels. Deviation from

management guidelines was minor in most circumstances

and most commonly occurred due to administration of

prophylaxis for P. jirovecii when it was probably not

required. Adherence to guidelines was not affected by the

involvement of a HIV specialist in the patient’s care.

Most importantly, length of stay was significantly pro-

longed in cases that were managed outside of recom-

mended guidelines when compared to appropriately

managed patients in the comparator group.

A trend towards extended length of stay was also seen

in any hospitalization where management deviated from

standard guidelines. Lastly, no persons in the case group

with a low absolute CD4 count and preserved CD4 per-

centage were diagnosed with an AIDS related opportun-

istic infection.

Sudden declines in absolute CD4 count associated

with acute illness in non HIV infected patients have been

previously reported [7,8]. Beck investigated the effects of

active pulmonary tuberculosis on lymphocyte subsets,

finding that individuals infected with tuberculosis had

significantly lower absolute CD4 counts than uninfected

patients (748 cells/mm3 compared to 1043 cells/mm3).

Challenges in Managing Hospitalized HIV Infected Persons with Low Absolute CD4 and Preserved CD4 Percentage 243

No data regarding CD4 percentage was recorded by this

group [7]. Williams evaluated the effects of various

forms of acute infection on lymphocyte subpopulations.

Patients with pneumonia or respiratory infections (574

cells/mm3; 45%) and generalized sepsis (669 cells/mm3;

43.9%) had significantly lower absolute CD4 counts and

percentages than comparator groups of healthy patients

aged 21 - 53 years (1075 cells/mm3; 52.5%) and 67 - 88

years (924 cells/mm3; 52.6%) [8]. Thus, it is not surpris-

ing that we found significant declines in the absolute

CD4 count associated with acute illness in persons hos-

pitalized with HIV infection.

The mechanism of the sudden decline in absolute CD4

count associated with acute illness or injury may be ex-

plained by a stress reaction that leads to a reduction in

the total number of circulating lymphocytes and increase

in the number of neutrophils, commonly known as a “left

shift.” As neutrophils demarginate and enter circulation,

lymphocytes shift to the lymphatic-reticular systems,

altering the balance within the bloodstream. There is no

evidence that total body CD4 counts decline in this situa-

tion. Thus, the absolute CD4 count can appear falsely

depressed. While the actual number of circulating lym-

phocytes has decreased, the relative CD4 percentage re-

mains nearly stable during acute illness. This could also

explain why the absolute CD4 count promptly returns to

baseline once the stress has been removed. It is also re-

assuring that no patients with the relative decline in ab-

solute CD4 count had an AIDS-related OI. This suggests

that the CD4 population remains functional despite lower

numbers in the bloodstream. It is unclear whether these

sudden changes result in altered immune protection, as

plasma CD4 cells represent <2% of the total CD4 cells in

the body.

Our results should be viewed carefully because of

several important limitations. Our overall sample size

may limit our ability to discern important differences.

There were very few deaths, making it difficult to evalu-

ate if management decisions would affect mortality. As

in all retrospective studies, we did not have uniform data

collection. Not all subjects were investigated equally,

thus, AIDS defining OIs could have been missed. We

believe this is unlikely since we reviewed subsequent

hospitalizations and visits beyond the study period and

no cases of AIDS defining OIs were found.

The management of acutely ill persons hospitalized

with HIV is always challenging. It may be prudent to

evaluate for AIDS-defining opportunistic infections in

persons with measured CD4 counts < 200 cells/mm3 be-

cause one cannot be certain that patients are adhering to

their antiretroviral therapy. Rapid declines in CD4 counts

have been reported shortly after discontinuing antiretro-

viral therapy [9]. However, in these cases, typically the

CD4 percentage declines as well. The inappropriate ad-

ministration of prophylaxis for Pneumocystis jirovecii is

unlikely to harm many patients. It is a very reasonable

clinical decision to provide prophylaxis if CD4 criteria

are met. However, the importance of this observation is

that it was associated with prolonged length of stay

which leads to added cost and the risk of harm. Indeed,

the inappropriate use of antibiotics has been associated

with emergence of resistant bacteria and should generally

be avoided.

The phenomenon of the significant decline in CD4

count with preserved CD4 percentage appears to occur in

HIV infected patients on stable antiretroviral therapy

with acute febrile illnesses or severe stressful conditions.

Discordant results between absolute inpatient and prior

recent outpatient CD4 counts and percentages in persons

on stable antiretroviral therapy should raise suspicion

amongst clinicians. CD4 count risk stratification based

upon the value obtained during an acute illness requiring

hospitalization may not always be accurate. Administra-

tion of unnecessary antibiotics, overutilization of proce-

dures, and excessive ordering of laboratory assays may

result from inappropriate risk stratification. Providers

tend to extend periods of inpatient observation in persons

with depressed CD4 counts to ensure resolution of illness.

These factors lead to prolonged hospitalizations with

increased risk of complication to the patient and cost to

the health care system. In conclusion, clinicians should

review prior and current CD4 counts, HIV viral loads,

and antiretroviral treatment history to adequately risk

stratify patients with HIV infection presenting with acute

illnesses to ensure that they avoid unnecessary interven-

tions and prolongation of hospitalization.

5. Acknowledgements

Potential Conflicts of Interest: SMB: None. CJF: None.

No financial support was received for the development

and performance of this study. The authors thank Ms.

Susan Groh for her expertise and assistance in the con-

duct of this project.

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