Predictive markers of HIV-related weight loss and determination of differences between populations with weight loss stratified by opportunistic processes.

OBJECTIVE: To describe factors predictive of >10% weight loss among enrolled participants in clinical trials of the AIDS Clinical Trial Group (ACTG). DESIGN: A retrospective analysis of data from selected ACTG antiretroviral clinical trials completed prior to 1996 (ACTG 116, 117, 155, 175, and 241), which did not include protease inhibitors. METHODS: Data were analyzed in Cox proportional hazards models to determine significant predictors for >10% weight loss while on study. Weight loss occurring within 30 days before or after an opportunistic infection (OI) was defined as "OI-associated." Both univariate and multivariate models were considered; gender-specific models were also analyzed to provide insight into potential gender differences in predictors of weight loss. RESULTS: We found that substantial weight loss is a frequent occurrence among those enrolled in clinical trials of antiretroviral agents; approximately 15% of subjects in the studies considered experienced >10% weight loss. CD4 cell count and HIV-1 RNA at week 8, Karnofsky score, and injection drug use status were significant multivariate predictive markers for weight loss associated with an OI; baseline weight, hemoglobin, triglycerides, and gender were additional predictors for weight loss not associated with an OI. CONCLUSIONS: This is the first study to characterize the association between baseline viral load and future weight loss. Baseline and week 8 immunologic parameters as well as measures of baseline symptomatology were significant predictors of weight loss associated and not associated with an OI.

Response to treatment with the leukocyte-derived immunomodulator IMREG-1 in immunocompromised patients with AIDS-related complex. A multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if a 6-month course of therapy with IMREG-1, a leukocyte-derived immunomodulator, slows disease progression in patients with AIDS-related complex. DESIGN: Randomized, double-blind trial. SETTING: Five academic- and three community-based clinics. PATIENTS: Immunocompromised patients (143) with HIV. INTERVENTIONS: IMREG-1 or placebo every 2 weeks (13 doses). MAIN RESULTS: Twelve of forty-eight patients on placebo and 5 of 95 patients on IMREG-1 experienced adverse events (AIDS-defining opportunistic infection or neoplasm, wasting syndrome, HIV-associated encephalopathy, or peripheral sensory neuropathy). Based on an intention-to-treat analysis, Kaplan-Meier event probabilities were 26% for the placebo group and 6% for the IMREG-1 group (P less than 0.001); based on the Cox proportional hazards model, the relative risk for patients on placebo compared with patients on IMREG-1 was 5.1 (95% CI, 1.8 to 14.8). The frequency of symptoms significantly increased from baseline in patients receiving placebo. The mean decrease in CD4+ cells from baseline was 80 x 10(6) cells/L in the placebo group and 29 x 10(6) cells/L in patients on IMREG-1, with 20% (8) and 38% (32) of patients, respectively, showing a trend toward an increase (P = 0.04). In patients receiving IMREG-1, the size and rate of delayed hypersensitivity responses were larger than in the placebo group. CONCLUSIONS: Patients with AIDS-related complex experienced fewer adverse events and constitutional symptoms after IMREG-1 treatment. The slower loss of CD4+ cells and increased size and rate of delayed hypersensitivity responses most likely reflect the effect of IMREG-1 on the immune system. No toxicity related to IMREG-1 administration was observed.