Combination Therapy With Protease Inhibitor Decreases Mortality Among HIV-Positive Children, Adolescents
Antiretroviral therapy that includes a protease inhibitor can reduce mortality among HIV-positive children and adolescents by 67%, according to a study published in the Nov. 22 issue of the New England Journal of Medicine. Current HIV treatment guidelines recommend that HIV-positive adults and children be treated with combination antiretroviral therapy that includes a protease inhibitor. To chart the effects of protease inhibitors on children and adolescents, researchers from the Harvard School of Public Health followed for four years 1,028 HIV-positive children who had enrolled in the Pediatric AIDS Clinical Trials Group Protocol 219 before Jan. 1, 1996. Study participants ranged in age from zero to 20 years and were categorized according to sex, race, age, educational level of parent or guardian and probable time of infection (perinatal or non-perinatal).
At the beginning of the study, 86% of participants were receiving only nucleoside reverse-transcriptase inhibitors, 9% were receiving nonnucleoside reverse-transcriptase inhibitors, 3% were receiving no antiretroviral medications and 2% of patients' treatment regimens were unknown. No participants were receiving combination therapy including a protease inhibitor. In 1996, the year combination therapy with a protease inhibitor first became available, only 7% of participants were receiving protease inhibitor combination therapy. However, by 1999 73% of subjects were receiving such therapy. The researchers found that participants who were not infected perinatally, were between six- and 20-years-old and who had a T cell ratio of less than 15% received combination therapy with a protease inhibitor sooner than younger, perinatally infected children who had higher T cell ratios. On average, participants received therapy with a protease inhibitor two years after Jan. 1, 1996. Mortality among participants declined from 5.3% in 1996 to 2.1% in 1997, 0.9% in 1998 and 0.7% in 1999, inversely related to the percentage of participants on protease inhibitors.
The researchers determined that initiation of combination therapy with a protease inhibitor reduces the risk of death in HIV-positive children and adolescents by 67%. Although whites and non-whites did not differ greatly regarding time to protease-inhibitor therapy initiation after being adjusted for severity of illness, the researchers note that the initial disparities indicate that "vigilance is needed to ensure equitable access to treatment for HIV." In addition, the researchers also write that extended antiretroviral therapy in children and adolescents may cause short- or long-term adverse reactions that should be taken into consideration. The authors conclude, "The benefits of combination therapy including protease inhibitors in children and adolescents with HIV include a decreased risk of death, improved growth, better immune function and a marked decrease in the incidence of infectious complications" (Gortmaker et al., NEJM, 11/22).
New Therapies Change the Face of Pediatric HIV
The face of pediatric HIV infection "has changed markedly" in the nearly 20 years since the first reported cases of HIV infection in children, Drs. John Sullivan and Katherine Luzuriaga of the University of Massachusetts Medical School write in an accompanying NEJM editorial. The availability of "potent" antiretroviral drugs has altered the course of the disease in children, but there are also several challenges to these new developments, they state. Sullivan and Luzuriaga write that antiretroviral therapy requires adherence to "complex and demanding regimens" and that the drugs can produce toxic side effects. In addition, use of the drugs can contribute to drug-resistant strains of HIV, although "promising second-generation drugs" and new classes of antiretrovirals are currently being tested. As many new HIV infections are occurring among children in developing nations, which do not have access to drug therapy, the United States and other countries and agencies must focus on developing inexpensive triple-drug antiretroviral therapy for all HIV-positive pregnant women and children, the authors state. Sullivan and Luzuriaga conclude, "These efforts would represent an important step toward changing the face of pediatric HIV infection for the many millions who are affected by it around the world" (Sullivan/Luzuriaga, NEJM, 11/22).