Barbara Starrett

Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.

OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

Trichosanthin, a ribosomal inhibitor protein, blocks HIV replication in lymphocytes and macrophages. This agent was used to treat 51 patients with advanced HIV disease in a dose-escalation study in which three injections were administered over a 9-21-day period in a dose range of 10-30 micrograms/kg per injection. The maximum tolerated dose was estimated to be 30 micrograms/kg. Reversible but severe fatigue and myalgias were the major dose-limiting side-effects; mild leucocytosis and elevations in serum transaminases were noted and were reversible. Non-dose-related reversible mental status changes were seen in six patients and were considered to be associated with the drug. This was usually manifest as dementia, but progressed to coma in two patients. This reversed, but the sequelae resulted in death in one patient. Decreases in serum p24 antigen levels were noted 1 month after the first infusion in 10 of 18 patients who entered the study with elevated levels; one converted to negative. Values usually remained low to the end of the study period (2 months). In those patients with CD4+ cell levels greater than 50 x 10(6) cells/l significant decreases in sedimentation rate and increases in CD4+ cell numbers were also noted. These changes were found at all dose levels but only in patients receiving three infusions.

OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

We report a case of prostate abscess due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome. The diagnosis and management are discussed, and the literature is reviewed.