anemia

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The prevalence of anemia in HIV-infected persons has not been well characterized in the HAART era. In a single-

center, retrospective study, anemia prevalence and risk factors, including use of HAART, were assessed in an

ambulatory clinical cohort of 758 HIV-infected patients for the calendar year 2000. The relationships between anemia

(hemoglobin level less than 12.5 g/dL) and demographic variables, antiretroviral treatment regimens, and disease

markers were analyzed. Mean baseline patient characteristics were hemoglobin level, 13.7 ± 1.9 g/dL; CD4 + cell

count, 405 ± 293/µL; and HIV RNA level, 77,841 ± 148,394 copies/mL. Overall anemia prevalence was 30.3%.

Multivariate logistic regression analysis demonstrated that anemia was associated with a CD4 + cell count below 50/

µL, female sex, black race, a viral load above 100,000 copies/mL, zidovudine use, and older age. Severe anemia was

less prevalent in this study population than in historical comparators; however, mild to moderate anemia rates remain

high.

Anemia is a common and serious complication of both HIV infection and its treatment.[1] In the setting of HIV

infection, anemia has been associated with decreased quality of life, functional status, and survival.[2-7] Antiretroviral

therapy, particularly HAART, has been associated with a decrease in the incidence and severity of anemia in HIV-

infected patients who have received a HAART regimen for at least 1 year.[1,8,9]

However, recent large, multicenter studies of patients receiving HAART suggest that decreases in hemoglobin (Hb)

level still occur among these patients and are predictors of poor clinical outcomes.[4,10,11] These studies also

indicate that several demographic and clinical factors are associated with an increased risk of anemia. These factors

include female sex, black race, low CD4+ cell count, high plasma HIV RNA levels, current use of zidovudine, and a

history of clinical AIDS.[9-11] Large multicenter studies provide valuable data on the prevalence of anemia across a

broad range of patients. However, the number of patients from each site may be small, and there is a risk that

differences in standard-treatment protocols among sites may play a role in the interpretation of data.

In order to gain further practical data on the prevalence of anemia in a typical clinical practice setting, we conducted a

study of anemia among the HIV-infected patients treated in our clinic during the course of 1 year. The primary

objective was to determine the prevalence of anemia and its clinical and demographic correlates in a cohort of HIV-

infected patients receiving care in a single-center public health setting in the HAART era. The secondary objective

was to identify the predictors of anemia in this patient population.

The retrospective manual review of patients' charts and cross-sectional analysis were conducted at the Hillsborough

County Health Department Specialty Care Clinic in Florida. All active patient charts dated January 1, 2000, through

December 31, 2000, were reviewed. Institutional Review Board approval was obtained before data collection. Waiver of

informed consent was granted based on the minimal risk the research posed to patients and the conclusion that such

a waiver did not violate patients' rights.

Data were collected from all patient records for the year 2000 that included any Hb level and an HIV RNA level

measured within 30 days of the Hb level. Collected data were recorded on forms that included patient age, sex,

race/ethnicity, Hb level, CD4+ cell count, plasma HIV RNA level, history of AIDS-defining illness, and antiretroviral

therapy regimen (including the dates and nature of any changes in treatment). In addition, the use of any medications

or supplements that could affect anemia (iron sulfate, iron gluconate, vitamin B12, folate, erythropoietin, testosterone)

was recorded.

Anemia Prevalence and Associated Risk Factors in a Single-Center Ambulatory HIV Clinical CohortTodd S. Wills, MD, Jeffrey P. Nadler, MD, Charurut Somboonwit, MD, Albert Vincent, PhD, Gerhard Leitz, MD, PhD, Kimberly

Marino, Eknath Naik, MD, PhD, Stacy Powers, MPH, Nadeem Khan, MD, Brent Laartz, MD

AIDS Read. 2004;14(6)

http://www.medscape.com/



Charts were excluded if both a change in antiretroviral drug class and a change in Hb level beyond the threshold of

12.5 g/dL (in either direction) occurred during the calendar year. Anemia for both men and women was defined as Hb

level of 12.5 g/dL or less. Although most laboratory reference ranges for Hb vary based on sex, this study used the

same definition of anemia for both sexes, given the lack of evidence in earlier studies to show that quality of life or

survival changes based on Hb level in HIV infection are sex-specific.[5] Patients' physicians or other primary care

providers were notified if any patients were found to be anemic during data collection to allow for further evaluation and

management, as appropriate.

HAART regimens were defined as either any antiretroviral regimen that included a nonnucleoside reverse

transcriptase inhibitor (NNRTI) or protease inhibitor (PI) in combination with other antiretroviral agents, or a triple–

nucleoside reverse transcriptase inhibitor (NRTI) regimen. For the purposes of this analysis, 8 antiretroviral regimens

were identified: no antiretroviral treatment (R1), triple-NRTI therapy that included zidovudine (R2), dual-NRTI plus PI

(including zidovudine) (R3), dual-NRTI plus PI (no zidovudine) (R4), dual-NRTI plus NNRTI (including zidovudine) (R5),

dual-NRTI plus NNRTI (no zidovudine) (R6), any other combination that included zidovudine (R7), and any other

combination that did not contain zidovudine (R8). Those regimens consisting of only 2 NRTIs were defined as non-

HAART regimens. Only antiretroviral therapy data for the calendar year 2000 were collected from the charts.

If any Hb value of 12.5 g/dL or less was recorded during the year, the nadir Hb level was recorded in order to obtain a

record of the entire population that had ever been anemic ("ever-anemic" group). Univariate chi-square analyses were

performed for those patients who were ever anemic, examining the following demographics: age, sex, race/ethnicity,

clinical disease status (HIV-infected, immunologic AIDS [evidence of HIV infection and CD4+ cell count of less than

200/µL], or clinical AIDS [evidence of HIV infection and history of AIDS-defining illness]), and drug treatment class

(R1 to R8, as described above). For this analysis, the baseline Hb level was the first Hb measurement for which there

was a viral load reading within 30 days. The Mann-Whitney U test was performed for correlation of sex, CD4+ cell

counts, and viral load readings with baseline Hb levels of 12.5 g/dL or less.

Multivariate logistic regression analysis was employed to identify risk factors for anemia. These included the

demographic variables of age (in 5- and 10-year intervals); race/ ethnicity (black vs white); sex; and clinical variables

of AIDS history, including CD4+ cell count (cell count intervals of 0 to 49, 50 to 199, 200 to 349, 350 to 499, and 500

or more), viral load (by 2-log and 3-log intervals), and duration of HIV infection.

For this study, 1278 patient charts were screened, and 758 were included in the study. The remaining 520 were

excluded because they either did not have complete data or met 1 or more of the exclusion criteria. Baseline CD4+

cell count and viral load data were not available for the entire screened population, and the absence of these data was

the primary reason for exclusion.

The demographic and mean base line clinical characteristics of the study population are summarized in . The study

population was not able for being highly treatment-experienced, with 633 patients receiving antiretroviral therapy; the

mean CD4+ cell count was 405/µL. Demographic characteristics of the study population were similar to those of the

general clinic population.

Table 1. Baseline Patient Demographics, Disease Status, and Treatment

Characteristic Total population

Patients enrolled 758

Age (y)

Mean 40

Range 17 - 69

Sex (n)



Male 530 (70%)

Female 228 (30%)

Race (n)

White 289 (38%)

Black 376 (50%)

Hispanic 88 (12%)

Other 5 (< 1%)

Mean hemoglobin level (g/dL) 13.7 ± 1.9

CD4+ cell count (/µL)

Mean 405 ± 293

Median (range) 374 (1 - 2305)

HIV RNA level (copies/mL)

Mean 77,841 ± 148,394*

Median (range) 9696 (51 - 750,000)

Patients with AIDS (n)

AIDS-defining illness 107

CD4+ cell count < 200/µL only 152

Duration of AIDS (y)

Mean 5.06 ± 1.10

Median (range) 3.98 (0 - 19)

Patients receiving antiretroviral treatment (n)

HAART 633 (84%)

Non-HAART therapy 18 (2%)

No treatment 107 (14%)

*Standard deviation exceeds mean viral load value secondary to wide discrepancy of absolute values.

Of the 758 evaluable patients, 30.3% (230) were anemic (Hb level of 12.5 g/dL or less) at some time during the study.

Figure 1 shows the distribution of Hb levels by 1-g increments in the ever-anemic patient group. The majority of the

ever-anemic patients (67%; 154 of 230) had a nadir Hb level of 12.0 to 12.5 g/dL, which was considered mild to

moderate anemia. Anemia was more prevalent among female patients than male patients: 54.0% and 20.2%,

respectively (P = .0001). The prevalence of anemia in this study was greater in black patients (44.7%; 168 of 376)

than in white patients (14.5%; 42 of 289), and this difference was statistically significant (P = .0001). Black women in

the study population had the highest prevalence of anemia (66.2%). The prevalence of anemia in black men was

32.1%; in white women, 27.9%; and in white men, 11.0%.



Distribution of hemoglobin levels in the ever-anemic patient group.

The prevalence of anemia was greater in patients with more advanced HIV disease. Of patients with CD4+ cell counts

of less than 200/µL and no AIDS-defining illness (n = 152), 46.1% were anemic. Of patients with clinical AIDS (n =

107), 46.7% were anemic. These prevalence rates were significantly higher than those in the patients with no AIDS

diagnosis in univariate analysis (P = .00005).

Figure 2 shows the prevalence of anemia at any time during the study by treatment regimen. No significant

differences in prevalence were found in patients receiving HAART (n = 633) compared with those on non-HAART

treatment regimens (n = 18). Anemia was significantly more prevalent in patients who were currently being treated

with HAART regimens containing zidovudine (groups R2, R3, R5, and R7) than in patients treated with non–

zidovudine-containing HAART regimens (groups R4, R6, and R8; P> .0001) ( ). The exception was those patients

treated with zidovudine-containing regimens that also included an NNRTI (R5 vs R6; P = .16).

Table 2. Variables Associated With Anemia as Calculated From Multivariate Logistic Regression Analysis

Variable Number of patients Odds ratio 95% CI P value

Patient demographics

Age* 758 1.04 1.02 - 1.07 .001

Age5 758 1.24 1.09 - 1.42 .0011

Age10 758 1.55 1.19 - 2.01 .0011

Black 376 4.13 2.52 - 6.79 .0001



Female 228 6.79 3.98 - 11.60 .0001

Disease status

AIDS (immunologic or clinical) 259 1.80 1.00 - 3.26 .05

Years with AIDS† 259 0.97 0.94 - 1.02 .3066

HIV RNA level >

100,000 copies/mL

104 1.95 1.04 - 3.66 .02


< 50 66 14.10 4.86 - 40.87 .0001

< 200 136 4.17 1.60 - 10.86 .0034

< 300 143 4.40 1.92 - 10.09 .0005

< 500 182 2.15 0.96 - 4.85 .063

Treatment regimen

R3 (ZDV + NRTI + PI) vs

R4 (2 NRTIs + PI; no ZDV)

137

155

3.15 1.87 - 5.32 .0001

R5 (ZDV + NRTI + NNRTI) vs

R6 (2 NRTIs + NNRTI; no ZDV)

163

116

1.45 0.86 - 2.44 .16

R7 (any other regimen with ZDV) vs

R8 (any other regimen without ZDV)

12

48

1.68 0.42 - 6.66 .45

All regimens with ZDV vs

all regimens without ZDV

332

319

2.06 1.46 - 2.90 .0001

CI, confidence interval; ZDV, zidovudine; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor;

NNRTI, nonnucleoside reverse transcriptase inhibitor.

*Age was analyzed as a continuous variable, with anemia risk increasing linearly with increasing age. Age5 and

Age10 refer to anemia risk with age when calculated in 5- and 10-year intervals, respectively.

†Years with AIDS was analyzed as a continuous variable.



Prevalence of anemia (defined as hemoglobin level of 12.5 g/dL or less) according to treatment regimen. (ZDV,

zidovudine; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; NNRTI, nonnucleoside reverse

transcriptase inhibitor.)

+ Cell Count, and Viral Load

Figure 3 shows the distribution of baseline Hb values in men and women by 1-g Hb increments. In this study, 4.8% of

women and 1.3% of men had Hb levels of less than 10 g/dL, consistent with severe anemia. Baseline Hb levels

between 10 g/dL and less than 11 g/dL were found in 6.2% of women and 1.5% of men. Baseline Hb values between

11 and 13 g/dL, consistent with mild to moderate anemia, were found in 31.2% of women and 10.1% of men.



Distribution of hemoglobin level by sex.

An increased prevalence of baseline anemia was associated with several clinical factors. Lower baseline CD4+ cell

counts were associated with lower baseline Hb values (Figure 4A). In patients with CD4+ cell counts of less than 200/

µL, 38.6% had an Hb level of less than 13 g/dL, compared with 12.2% of patients with a CD4+ cell count of 500 or

more/µL (P = .0001). Higher baseline viral load was associated with lower baseline Hb values (Figure 4B). In patients

with HIV RNA levels of greater than 30,000 copies/mL, 37.5% had a baseline Hb level of less than 13 g/dL, compared

with 16% of those with HIV RNA level of less than 500 copies/mL, but this difference was not significant.



Baseline hemoglobin levels: A, by CD4+ cell count strata (cumulative) and B, by viral load strata (cumulative).

Using multivariate logistic regression analysis, risk factors for anemia were identified ( ). An increased risk of anemia

was found to be associated with CD4+ cell counts of less than 50/µL, female sex, black race, treatment regimens

containing zidovudine (with the exception of those zidovudine-containing HAART regimens that include an NNRTI),

viral load of greater than 100,000 copies/mL, and older age. The presence of an AIDS diagnosis was not an

independent risk factor for anemia in multivariate logistic regression analysis, although markers of disease

progression, such as decreasing CD4+ cell count and increasing viral load, remain independent predictors of risk.



Table 2. Variables Associated With Anemia as Calculated From Multivariate Logistic Regression Analysis

Variable Number of patients Odds ratio 95% CI P value

Patient demographics

Age* 758 1.04 1.02 - 1.07 .001

Age5 758 1.24 1.09 - 1.42 .0011

Age10 758 1.55 1.19 - 2.01 .0011

Black 376 4.13 2.52 - 6.79 .0001

Female 228 6.79 3.98 - 11.60 .0001

Disease status

AIDS (immunologic or clinical) 259 1.80 1.00 - 3.26 .05

Years with AIDS† 259 0.97 0.94 - 1.02 .3066

HIV RNA level >

100,000 copies/mL

104 1.95 1.04 - 3.66 .02


< 50 66 14.10 4.86 - 40.87 .0001

< 200 136 4.17 1.60 - 10.86 .0034

< 300 143 4.40 1.92 - 10.09 .0005

< 500 182 2.15 0.96 - 4.85 .063

Treatment regimen

R3 (ZDV + NRTI + PI) vs

R4 (2 NRTIs + PI; no ZDV)

137

155

3.15 1.87 - 5.32 .0001

R5 (ZDV + NRTI + NNRTI) vs

R6 (2 NRTIs + NNRTI; no ZDV)

163

116

1.45 0.86 - 2.44 .16

R7 (any other regimen with ZDV) vs

R8 (any other regimen without ZDV)

12

48

1.68 0.42 - 6.66 .45

All regimens with ZDV vs

all regimens without ZDV

332

319

2.06 1.46 - 2.90 .0001

CI, confidence interval; ZDV, zidovudine; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor;

NNRTI, nonnucleoside reverse transcriptase inhibitor.

*Age was analyzed as a continuous variable, with anemia risk increasing linearly with increasing age. Age5 and

Age10 refer to anemia risk with age when calculated in 5- and 10-year intervals, respectively.



†Years with AIDS was analyzed as a continuous variable.

This study provides a unique analysis of the prevalence of anemia in HIV-infected patients. It presents the

demographic and clinical correlates of anemia in a single-center cohort of HIV-infected patients with a diverse profile

receiving care in a public health setting well into the HAART era. Previous studies of anemia in HIV-infected patients

were conducted either before the HAART era or early in the HAART era,[2,9] across multiple treatment sites,[4,10,12]

or with a select patient population with limited diversity (eg, women only).[8,11,13]

The use of a single-center cohort reduces the likelihood of differences in clinical assessment and treatment protocols

that might be the case across a large number of treatment sites. Although multicenter studies have provided a valid

picture of the prevalence of anemia in HIV-infected patients, they may have been limited because of the small number

of patients enrolled from each treatment site. Our study had a patient population of 758 men and women.

Our data confirmed the high prevalence of mild to moderate anemia in HIV-infected patients treated with HAART. The

overall prevalence of anemia (Hb level 12.5 g/dL or less) in this population was 30.3%. These data indicate a higher

prevalence of anemia than that reported in the most recent large, multicenter study of anemia prevalence in an HIV

population in the HAART era.[10] In that study, an overall prevalence of anemia (Hb level 12 g/dL or less for women

and less than 13 g/dL for men) of 22% was found, with a higher prevalence in women (32%) than men (19%). That

study also found a higher prevalence of anemia among black women and black men (39% and 31%, respectively)

than in white women and white men (19% and 12%, respectively).

We also confirmed the finding of a higher prevalence of anemia among women and blacks in our cohort. In our

population, anemia was found in 54.0% of women and 20.2% of men. The prevalence of anemia was 44.7% in black

patients and 14.5% in white patients. This compares with reported anemia rates of 2.2% in men, 2.3% in women,

1.0% in whites, and 3.2% in blacks in a cross-section of the US population.[14] We found the highest prevalence of

anemia in black women (66.2%)—more than double the prevalence in black men (32.1%) and white women (27.9%)

and more than 6 times that found in white men (11.0%). Three studies in women-only multicenter populations in the

HAART era have also shown a significantly higher prevalence of anemia among black HIV-infected women than in

white HIV-infected women.[8,11,13] In these studies, anemia was defined as an Hb level of less than 12 g/dL.

While it appears that the widespread use of HAART has resulted in a decrease in the prevalence of more severe

anemia in HIV-infected patients, mild to moderate anemia may be increasing in prevalence. One study of anemia

conducted before the HAART era (1989 to 1996) in a large urban HIV clinical practice found grade 1 anemia (Hb level

less than 8.0 to 9.4 g/dL) in 12% of patients (men and women).[2] There are no data on the prevalence of less severe

anemia (ie, 12.5 g/dL or less) in this study population. In a study conducted with a similar patient population early in

the HAART era, overall, 11% of patients (men and women) had an Hb level of 10 g/dL or less and 27% had an Hb

level of 10 to 12 g/dL.[9]

In our study, a lower percentage of patients had Hb levels of less than 10 g/dL (4.8% of women and 1.3% of men)

than in these previous studies. Mild to moderate anemia remained prevalent in this study population, with 31.2% of

women and 10.1% of men demonstrating baseline Hb levels between 11 and 13 g/dL. Our study provides further

evidence that the prevalence of more severe anemia (Hb level less than 10 g/dL) may be declining in HIV-infected

patients in the HAART era and that the prevalence of mild to moderate anemia is increasing.

This investigation demonstrated a significantly increased risk of anemia associated with female sex, black race,

increased age, advanced HIV disease, and treatment with HAART regimens that include zidovudine. The highest risk

of anemia, however, was found to be associated with advanced HIV disease. Patients with CD4+ cell counts of less

than 50/µL had a 6-fold increased risk of anemia compared with patients with CD4+ cell counts of less than 500/µL. In

addition, patients with viral loads above 100,000 copies/mL were almost twice as likely as patients with lower viral

loads to have anemia. These data confirm previous findings of an increased risk of anemia associated with advanced

HIV disease.[10,11,13]



We found no significant difference in the prevalence of anemia between patients receiving HAART and those not

receiving HAART, confirming the results of other studies.[8,13] We did, however, find an increase in the risk of anemia

associated with the use of some zidovudine-containing HAART regimens. Patients treated with zidovudine-containing

HAART regimens were found to have a risk of anemia 1.45 to 3.15 times that of patients treated with similar regimens

without zidovudine. The greatest treatment-related risk of anemia was associated with treatment regimens containing

2 NRTIs (1 of which was zidovudine) and a PI. In contrast, Moore and Forney[9] found no effect of the use of

zidovudine-containing regimens on the prevalence of anemia.

There are several limitations to the interpretation of the results of this study. Because of sample-size constraints, we

did not assess the effect of different treatment regimens or of any individual antiretroviral agents, with the exception of

zidovudine, which limits the ability of the study to correlate anemia with specific treatments. The finding that the

correlation between increased risk of anemia and the use of zidovudine was not seen in patients on NNRTI-containing

regimens may have been better explained had we been able to examine the effect of select individual regimens.

Further, the study did not assess the difference in anemia prevalence between those patients receiving HAART and

those patients not receiving HAART with other variables controlled. In addition, we did not control for the use of

treatments that may have an effect on Hb level (eg, ribavirin, ganciclovir, testosterone, ferrous sulfate, recombinant

human erythropoietin) in patients receiving such therapy (n = 51). Finally, the data collection methods of this study

did not allow for a separate analysis of the correlation of the demographic and clinical variables on anemia in the

female patients.

The data presented here provide evidence of a high prevalence of mild to moderate anemia in HIV-infected patients.

These data confirm similar findings of a recent multicenter anemia prevalence study.[10] These findings help to refine

our understanding of the prevalence of anemia in the HAART era. While HAART use has been associated with a

reduction in the incidence of severe anemia in HIV patients,[8,9] mild to moderate anemia prevalence remains high.

This is particularly true for women and blacks with HIV infection.

Other studies of HIV-infected patients have shown an association between anemia and decreased quality of life,

decreased functional status, increased fatigue, increased risk of disease progression, and decreased survival.[3,6,9,15,16] Some studies have suggested that the treatment of anemia in HIV-infected patients may be associated

with a decreased risk of death.[1,2,15] Because of the negative impact of anemia on HIV-infected patients, a greater

awareness of the risks of anemia and its sequelae in these patients seems warranted.

Although our study did not assess the effect of medical intervention intended to improve or maintain Hb levels in our

patients, we believe that the results suggest that because of its prevalence, particularly among certain higher-risk

groups, including women and blacks, greater attention should be paid to Hb levels in HIV-infected patients and to the

consideration of medical intervention, if warranted.

Anemia has been known to be a common complication of HIV infection since early in the epidemic. Sullivan and

colleagues[1] published the largest study describing the prevalence of anemia before the availability of HAART. In

more than 31,000 patients from the CDC Adult and Adolescent Spectrum of HIV Disease Surveillance Study, the 1-

year incidence of anemia (defined as a hemoglobin level of less than 10 g/dL) ranged from 3.2% in asymptomatic

HIV-infected patients, to 12.1% in patients with immunologic AIDS, to a high of 36.9% in patients who had had an

AIDS-defining illness. In addition to advancing HIV disease, risk factors for anemia included black race, female sex,

and use of myelotoxic drugs, such as zidovudine.

Since the introduction of HAART, several studies have examined the prevalence of anemia, indicating that the

prevalence of severe anemia has declined while mild to moderate anemia remains relatively common.[2-4] The article

by Wills and colleagues[5] reports the prevalence of anemia and associated factors in a clinic in Florida during

calendar year 2000. This cross-sectional analysis was done by retrospective review of patients' medical records. The

definition of anemia was the same for women and men: hemoglobin level of less than 12.5 g/dL. In this study, the

overall prevalence of anemia was 30%, with the majority of patients having mild anemia and hemoglobin levels within



the range of 12 to 12.5 g/dL. As in earlier studies, the authors also found a strong association between anemia and

decreasing CD4 cell count, female sex, black race, and increased age.

One of the difficulties in comparing studies of the prevalence or incidence of anemia has been the differing definitions

of anemia used, with many of the earlier studies using hemoglobin level thresholds of 10 to 11 g/dL to define anemia.

The study by Wills and associates uses a threshold of 12.5 g/dL; such use of a higher hemoglobin level threshold to

define anemia has become more acceptable because of a growing body of evidence that a hemoglobin level of

approximately 12 g/dL can be associated with significant declines in functional status and quality of life.[6-8] As HIV

infection has become a chronic disease with the use of HAART, what was previously considered a hemoglobin level

of little clinical consequence is now considered a degree of anemia that can compromise a patient's quality of life.

Lower levels of hemoglobin (eg, less than 10 g/dL) have now been shown to be associated with higher rates of

opportunistic illness and mortality in HIV-infected persons, after adjusting for other known surrogates for illness

severity, including CD4 cell level, viral load, previous AIDS-defining illness, age, and other factors.[1,2,9,10] Whether

this association between adverse clinical outcomes and severe anemia is causal is not currently known; at the very

least, anemia is an important prognostic marker for early death.[11]

The causes of anemia in HIV infection are myriad and include adverse effects of certain drugs (eg, zidovudine,

ganciclovir), nutritional deficits (eg, iron, folate, and vitamin B12 deficiencies), bone marrow infiltration (eg,

Mycobacterium avium complex infection, lymphoma) and, less commonly, hemolytic anemias and chronic bleeding.

When specific causes such as these are diagnosed, treatment should be targeted to the specific cause. However,

HIV infection itself may be the most common cause of anemia, either through direct infection of hematologic

precursor cells or through the effects of inflammatory cytokines following infection.

Hematopoietic growth factors are an effective therapy for the anemia of HIV infection, restoring hemoglobin levels in

HIV-infected persons who have an endogenous erythropoietin level of less than 500 IU.[6] Human recombinant

erythropoietin has specifically been shown to be an effective therapy in HIV infection for restoring hemoglobin levels

and decreasing the need for red blood cell transfusion.[6,12,13]

Of recent interest has been whether the use of HAART can directly treat anemia caused by HIV infection. Several

previous studies have consistently shown an association between the use of HAART and an increase in hemoglobin

levels.[2,3,14,15] Improvement of anemia and return to normal hemoglobin levels can occur within approximately 6

months. If zidovudine is part of the regimen, the beneficial effect on hemoglobin may be mitigated. The current study

by Wills and colleagues[5] showed an association between HAART and higher hemoglobin levels, although when

zidovudine was part of the HAART regimen the risk of anemia was higher. Of note, a lower viral load was also

associated with a higher hemoglobin level, suggesting the benefit when HAART is effectively lowering viral load. In

another study, when zidovudine was part of the HAART regimen, the hemoglobin response was as robust as when an

alternative nucleoside was used.[3] In my opinion, the jury is still out on whether zidovudine should be used as part of

the HAART regimen when anemia is present.

Anemia continues to be a common complication of HIV infection, although severe anemia appears now to be less

common with the advent of effective antiretroviral therapy. Even mild to moderate anemia can compromise a patient's

functional status and quality of life and should not be ignored. Specific causes of anemia should be sought and

treated. If specific reversible causes are not present, the anemia of HIV infection will usually respond to hematopoietic

growth factors. It is now known that HAART can also be an effective treatment of HIV-associated anemia.

Richard D. Moore, MD, MHS

Professor, Medicine and Epidemiology

Johns Hopkins University



Baltimore

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infected persons: results from the multistate Adult and Adolescent Spectrum of HIV Disease Surveillance

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2. Mocroft A, Kirk O, Barton SE, et al. Anaemia is an independent predictive marker for clinical prognosis in HIV-

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4. Levine AM, Berhane K, Masri-Lavine L, et al. Prevalence and correlates of anemia in a large cohort of HIV-

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Ann Intern Med. 1992;117:739-748.

7. Revicki DA, Brown RE, Henry DH, et al. Recombinant human erythropoietin and health-related quality of life of

AIDS patients with anemia. J Acquir Immune Defic Syndr. 1994;7:474-484.

8. Abrams DI, Steinhart C, Frascino R. Epoetin alfa therapy for anemia in HIV-infected patients: impact on quality

of life. Int J STD AIDS. 2000;11:659-665.

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Funding information

This trial was funded by an unrestricted educational grant from Ortho Biotech Products LP.

AIDS Read. 2004;14(6) © 2004 Cliggott Publishing, Division of CMP Healthcare Media

16. Moyle G. Anaemia in persons with HIV infection: prognostic marker and contributor to morbidity. AIDS Rev.

2002;4:13-20.

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