Jill Lietzau

Parameters affecting the development of non-Hodgkin's lymphoma in patients with severe human immunodeficiency virus infection receiving antiretroviral therapy.

PURPOSE To investigate the occurrence of non-Hodgkins lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy and factors associated with the development of these lymphomas. PATIENTS AND METHODS The charts of 55 patients with advanced HIV infection receiving zidovudine (formerly known as azidothymidine [AZT])-based therapy and 61 patients receiving dideoxyinosine (ddI) were examined for the occurrence of NHL. Stored samples from the AZT-based treatment cohort were examined retrospectively for parameters predictive of the subsequent development of lymphoma. RESULTS Eight of 55 patients receiving AZT-based therapy developed NHL, yielding an estimated probability of 12% (95% confidence interval [CI], 4.7% to 27.1%) after 24 months, and 29.2% (95% CI, 15.2% to 48.7%) after 36 months. Four of 61 patients receiving ddI developed NHL, yielding a 6.2% (95% CI, 2.1% to 17%) estimated probability after 24 months, and 9.5% (95% CI, 3.6% to 22.8%) after 36 months. The difference between these cohorts was not significant (two-tailed P [P2] = .13). Patients with less than 50 CD4 cells/microL developed NHL at a significantly higher rate (P2 = .0085). This was particularly true for patients who presented with primary CNS lymphoma (PCNSL). For patients receiving AZT-based therapy, pretreatment serum interleukin-6 (IL-6) levels were somewhat higher in those who subsequently developed NHL than in those who did not (P2 = .048). CONCLUSION HIV-infected patients with profound immunodeficiency, especially those with less than 50 CD4 cells/microL, are at substantial risk of developing NHL and particularly PCNSL. Additional studies are needed to define the role of other factors such as IL-6 in the pathogenesis of these opportunistic tumors.

Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma.

PURPOSE To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposis sarcoma (KS). PATIENTS AND METHODS Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. RESULTS Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. CONCLUSION Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease.

CD4 Count and the Risk for Death in Patients Infected with HIV Receiving Antiretroviral Therapy

OBJECTIVE To investigate the relation between CD4 count and the immediate hazard of dying in patients receiving zidovudine (azidothymidine [AZT])-based antiretroviral therapy. SETTING A research hospital that recruits patients from the entire United States. DESIGN Retrospective analysis of a cohort of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex participating in long-term zidovudine-based antiretroviral protocols. PATIENTS Fifty-five patients with human immunodeficiency virus (HIV) infection and either AIDS or severe AIDS-related complex who were followed for as many as 4 years while they received antiretroviral therapy. MEASUREMENTS CD4 counts were measured. MAIN RESULTS Ten patients are known to be alive and 1 was lost to follow-up. Of the 44 patients who are known to have died, the CD4 range was known within 6 months of death in 41. All but 1 of these 41 assessable deaths occurred in patients whose CD4 counts were known to have fallen below 50 CD4 cells/mm3 (P less than 10(-10)). The hazard of dying in the cohort ranged from 0 deaths/patient-month (95% CI, 0 to 0.008 deaths/patient-month) in patients with 200 or more CD4 cells/mm3 to 0.07 deaths/patient-month (CI, 0.050 to 0.094 deaths/patient-month) in patients with fewer than 50 CD4 cells/mm3. For the patients who died and whose cases were assessable, the mean of the last three CD4 counts obtained before death was 7.7 CD4 cells/mm3 (CI, 0.9 to 63.3 cells/mm3). The median survival of patients once their CD4 counts fell below 50 CD4 cells/mm3 was 12.1 months (CI, 7.2 to 19.4 months). CONCLUSIONS In a carefully followed cohort treated with zidovudine-based antiretroviral therapy, nearly all deaths occurred in patients with fewer than 50 CD4 cells/mm3. These findings may have implications in the monitoring of patients with AIDS and in the use of CD4 count as a clinical trials end point for the antiretroviral therapy of HIV infection.

Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: A comparison of simultaneous and alternating regimens

Objective:To evaluate the effects of treatment with alternating and simultaneous regimens of zidovudine and didanosine on neuropsychological function in patients with symptomatic HIV-1 disease, focusing on patients with possible HIV-1-associated central nervous system (CNS) compromise at entry. Design:Randomized non-blinded clinical trial. Setting:Government medical research center. Patients:Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compromise at entry. Results:After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) were seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0.05). Improvements were also noted in receptive vocabulary, reading, perceptual discrimination and reasoning, divided attention, motor strength, and in mood and affect. Improvements in those latter functions were generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall difference between the two drug regimens in the effects on CNS parameters. Conclusions:Therapy-related improvements were noted particularly for patients with HIV-1-associated CNS compromise. Neuropsychological functions that have been implicated in AIDS dementia — memory and attention — showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens with regard to CNS measures. This supports the contention that the CNS constitutes a relatively independent compartment in terms of HIV disease and treatment.