Robert A. Livingston

A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection

BACKGROUND Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. METHODS In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. RESULTS The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). CONCLUSIONS In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.

Effect of Enteral Tube Feeding on Growth of Children with Symptomatic Human Immunodeficiency Virus Infection

Summary Malnutrition and growth failure are frequent clinical consequences of human immunodeficiency virus (HIV) infection in children. Tube feeding is a means by which to increase the enteral intake of nutrients. We examined the effect of tube feeding in 18 children, median age 6 months (range, 3–159). Tube feedings were initiated due to growth failure in all, which was also associated with dysfunctional swallowing or aspiration in seven children and gastroesophageal reflux in two. Tube feedings were infused via nasogastric tube (n = 4) or gastrostomy tube (n = 14) and were continued for a median of 8.5 months (range, 2–24). Stoma complications developed in three children with gastrostomy tubes; these were the only tube-related side effect. Tube feedings were discontinued due to noncompliance (n = 3), gastrostomy leakage (n = 2), intolerance (n = 2), and death (n = 3). Anthropometric changes were evaluated comparing mean standard deviation scores (Z) before and after tube feeding. Tube feeding resulted in significantly increased weight for age (Z, −2.13 + 0.7 vs. −1.46 + 1.4; p = 0.04), weight for height (Z, −1.07 + 1.0 vs. −0.13 + 1.0; p = 0.004), and arm fat area (Z, −1.75 + 1.3 vs. −0.62 + 1.2; p = 0.01). However, tube feeding did not result in significant changes in height for age (Z, −1.93 + 0.8 vs. −1.74 + 1.6) or arm muscle area (Z, −1.24 + 0.9 vs. −0.57 + 1.2). Tube feedings effectively increased the weight of HIV-infected children in this study, but they were not sufficient to correct linear growth deficits.

Human Immunodeficiency Virus Type 1 (HIV-1) gp120–Specific Antibodies in Neonates Receiving an HIV-1 Recombinant gp120 Vaccine

Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P=.01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission.

Safety and Immunogenicity of HIV Recombinant Envelope Vaccines in HIV-Infected Infants and Children

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

SAFETY AND IMMUNOGENICITY OF HIV RECOMBINANT ENVELOPE VACCINES IN HIV-INFECTED INFANTS AND CHILDREN. † 57

SAFETY AND IMMUNOGENICITY OF HIV RECOMBINANT ENVELOPE VACCINES IN HIV-INFECTED INFANTS AND CHILDREN. † 57