Prevention of Infection in HI

Abstract & Commentary

Synopsis: A recent study does little to clarify the controversial issue of whether immune globulin is an effective means of reducing serious infections in in HIV-infected patients.

Source: Kiehl MG, et al. Arch Intern Med 1996;56:2545-2550.

Kiehl and colleagues examined the benefits of the administration of intravenous immune globulin to patients with HIV infection. Patients in CDC classes B and C receiving AZT monotherapy were randomized to receive immune globulin 200-400 mg/kg every 21 days. Infections included laboratory-confirmed bacterial and opportunistic infection, as well as cytomegalovirus (CMV) disease as defined by the presence of early antigen. Infections without a known pathogen and all cases of acute sinusitis required confirmation by a second physician blinded to the treatment group.

A total of 171 patients were enrolled; 127 were evaluable. Baseline entry criteria for the two groups were similar with two important exceptions. The median CD4+ at entry count was 140 for patients who received immune globulin and 110 for control subjects. In addition, 19 of 57 (33.3%) vs. 13 of 70 (18.6%) of the treated vs. the control group were receiving prophylaxis with TMP-SMX.

The probability of remaining free of serious infection was significantly greater for patients who received immune globulin (median, 54 weeks) in comparison to the control group (26 weeks) (P < 0.001, log rank analysis). Death due to serious infection occurred in 17% vs. 35% of the treated vs. control patients, but this result did not reach statistical significance. While the percentage of patients with febrile illness was similar between groups, the number of days of fever and hospitalization were significantly lower in patients who received immune globulin.


Whether immune globulin is an effective means of reducing serious infections in HIV-infected adults remains controversial, and this study does little to clarify the issue. The fact that patients in the control group had lower CD4 counts and were less likely to have received TMP-SMX prophylaxis has obvious implications. In addition, 48 (27%) of those who were enrolled failed to meet the entry criteria or died within the first two weeks of study, and another 34 (20%) were censored for a variety of reasons, including discontinuation of AZT, use of other antiretroviral agents, and death due to non-infectious causes (14 vs 3 in the treated vs untreated groups, respectively). Additional information about these deaths and an uncensored analysis may have been helpful.

In a separate study, G-CSF, administered to patients with mild neutropenia (absolute neutrophil counts of 750-1000/mcL), and titrated to maintain a white blood count of 2000-10,000/mcL, was associated with a 54% reduction in severe bacterial infections (P = 0.02), as well as a reduction in hospital days (P = 0.02) (Kurittzkes D. Abstract # 365, Fourth Conference on Retroviruses and Opportunistic Infections). However, similar to the above study, the unblinded nature of this trial makes the interpretation of differences in certain infections and hospital days problematical.

The risk of serious infections in HIV-infected patients can be reduced by other means. A recent double-blind, placebo-controlled study demonstrated that azithromycin, administered in a dose of 1200 mg once weekly to patients with CD4+ counts less than 100/mm3, reduced the incidence of bacterial infections by 50% (most of which were bacterial pneumonias and sinusitis, but also included bacteremia). (Oldfield C, et al. Abstract # 203, Third Conference on Retroviruses and Opportunistic Infections, 1996.) These data suggest that a macrolide, used for Mycobacterium avium prophylaxis, may be the most cost-effective means for reducing the incidence of bacterial infections in patients with advanced AIDS disease.