III. Results

Data from the medical records of 32,867 patients were analyzed. Of these, 31,534 (96%) had at least one hemoglobin concentration abstracted. The distribution of the first abstracted value (prevalent concentration) is shown in Table 3. The distribution of hemoglobin strata varied dramatically with stage of HIV disease: For HIV-infected persons with no AIDS, 72% and 69% of men and women, respectively, had hemoglobin concentrations within the reference range (greater than 14 or 12 g/dL, respectively). However, for persons with clinical AIDS, only 13% and 23% of men and women, respectively, had hemoglobin concentrations within the reference range.

A total of 13,315 had sufficient follow-up time and all information required for analysis of incidence; the characteristics of persons who were included and those who were excluded were similar (Table 1). Incidence of anemia was associated with clinical stage of disease: 1-year incidence was 3.2% for 6,094 persons with HIV infection but not AIDS, 12.1% for 2,579 persons with immunologic AIDS (CD4 of <200/µL or CD4 percentage of <14), but not clinical AIDS, and 36.9% for 4,642 persons with clinical AIDS. In all groups there were 2,222 anemia diagnoses, of which 494 (22.2%) were drug related. Most diagnoses (1,311, 59%) were based only on low hemoglobin level; 505 diagnoses (23%) were based only on ICD-9 codes and 406 diagnoses (18%) were based both on hemoglobin level and ICD-9 codes. The incidence of anemia differed by race/ethnicity, stage of disease, presence of concurrent illnesses, and prescription of chemotherapeutic agents (Table 4). Anemia, whether drug-related or unrelated to drugs, was positively associated with clinical AIDS, a CD4 count of <200, bacterial septicemia, neutropenia, thrombocytopenia, prescription of ganciclovir, and prescription of fluconazole and negatively associated with the prescription of TMP-SMX. Additionally, drug-related anemia was positively associated with prescription of ZDV (Table 5). Anemia unrelated to drugs was also associated with black race, female sex, and lymphoma and was negatively associated with prescription of ZDV (Table 5).

Of 19,213 persons included in survival analysis (Table 2), 6,632 (35%) died during follow-up. Median follow-up time for all persons included was 17 months. Survival did not differ significantly for persons with a diagnosis of drug-related anemia versus those with a diagnosis of anemia unrelated to drugs (P = .3 by log rank test), so all anemic persons were considered together in the mortality analysis. Median survival was significantly shorter for persons with anemia than for those without anemia, regardless of first CD4 count (Table 6), Proportional hazards regression was used to control for CD4 count, clinical AIDS, age, neutropenia, thrombocytopenia, antiretroviral therapy, and Pneumocystis carinii pneumonia (PCP) prophylaxis. After controlling for these factors, anemia was significantly associated with increased risk of death at all levels of first CD4 count (Table 6). Stratified proportional hazards regression analysis showed that the effect of anemia on survival differed by first CD4 counts; for persons with a first CD4 count of <200 cells/µL, the risk ratio was 1.56 (99% CI, 1.43 to 1.71 summary data not shown in Table 6), but for persons with a first CD4 count of > or = 200 cells/µL, the risk ratio was 2.48 (99% CI, 2.14 to 2.88).

There were 7,261 anemic persons in the initial mortality analysis, of whom 3,203 (44%) had subsequent hemoglobin level determinations and were, thus, also included in analyses of the effect of recovery from anemia on mortality. The results of mortality analyses were not different for persons recovering from drug-related anemia or anemia unrelated to drugs, so all persons with anemia were considered together for these analyses. Of these, 1,341 (42%) were treated with either erythropoietin or blood transfusion and 1,208 (38%) recovered from anemia. Median survival was significantly longer for persons who recovered than for those who did not recover, regardless of first CD4 count (Table 7). When clinical AIDS, CD4 count, neutropenia, thrombocytopenia, antiretroviral therapy, and PCP prophylaxis were controlled, recovery from anemia was significantly associated with decreased risk of death (Table 7); there was no interaction with first CD4 count, and the combined risk ratio was 0.37 (99% CI, 0.33 to 0.43).