In a randomized, controlled double-blind study, 15 patients with AIDS-related complex/Walter-Reed 5 (ARC/WR5) were compared during 6 months intravenous immunoglobulin (IVIG) treatment (0.4g/kg body weight every 2 weeks) with 15 placebo-treated patients. This study was aimed at the lymphocyte response to T and B cell mitogens and antigens. 3H-thymidine uptake was determined after stimulation with the unspecific mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), formalinized Staphylococcus aureus-Cowan I (SAC), and with the antigens tuberculin and herpes simplex virus (HSV) at the onset, on days 85, 183, 267 and 351; IgG and IgM antibodies against HSV were measured by ELISA. In addition, 30 untreated HIV-negative controls were tested. For the T cell mitogen PHA, T-cell-dependent B cell mitogen PWM and B cell mitogen SAC, no differences between the two patient groups were observed before therapy nor in the course of therapy or the 6-month observation period thereafter. The entire patient group showed significantly impaired mitogenic response on day 1 as compared to the controls. There was no significant difference in response to tuberculin between the patients and HIV-negative controls, nor for both patients groups before and in the course of treatment. All patients had IgG antibodies against HSV. Three of them showed blastogenie lymphocyte response to HSV on day 1. Among 19 seropositive controls, 7 individuals showed positive HSV lymphocyte response; but for both patient groups, there was no significant difference before and in the course of the treatment and observation period. We concluded that, in spite of some clinical improvement regarding fever and fatigue during IVIG treatment of ARC/WR5 patients, there is no influence on lymphocyte function, as measured by response to mitogens and antigens.

The influence of high-dose intravenous immunoglobulins (HD-IVIG) on the clinical status and T4 cell count of adults with AIDS-related complex (ARC) and Walter-Reed 5 (WR5) was evaluated in a randomized double-blind longitudinal study. Inclusion criteria were: (1) T4 cells <400/µl and (2a) oral thrush or cutaneous anergy or (2b) two clinical ARC criteria (fever, diarrhea, weight loss, fatigue, night sweats). Thirty patients [28 males, 2 females, median age 41 (24-64) years] with ARC (n = 8), WR5 (n = 12) and both (n = 10) were stratified according to their T4 cell count (≥ vs. <300/µl). Fifteen patients received 0.4g/kg body weight IVIG and 15 placebo (albumin 0.03%) every other week for 26 weeks with follow-up for another 26 weeks. The clinical status was defined as a score consisting of fever, diarrhea, night sweats, fatigue, weight loss, oral candidiasis and mucosal or cutaneous herpes simplex. Clinical examination and routine laboratory assessments were performed before initiation of the study and before each administration, lymphocyte phenotyping every 4 weeks and cutaneous reaction, serology and lymphocyte stimulation every 12 weeks. Both groups were comparable in initial clinical symptoms and laboratory values. Seven patients developed AIDS (treatment group: 3, placebo group: 4), 1 patient died by homicide. After 26 weeks, the clinical score (particularly fatigue and fever) was significantly improved in the treatment group, while the T4 cell count and other clinical and immunological parameters remained unaltered. This limited effect was still evident at termination of the study after 52 weeks. In conclusion, HD-IVIG can improve the clinical status of patients with advanced HIV-1 infection without obviously correcting the underlying impaired cellular immunity. The substitution of intact antibodies in the state of functional hypogammaglobulinemia is suggested as possible therapeutic mechanism.