Protease Inhibitors in Children: Combination Therapy Reduced Death by Two Thirds

AIDS TREATMENT NEWS Issue #374, November 23, 2001
John S. James

A November 22 article in the NEW ENGLAND JOURNAL OF MEDICINE reported on a cohort of 1028 HIV-infected children studied from 1996 through 1999(1). After statistical analysis to adjust for the fact that those starting treatment tended to be sicker, the study found that introduction of an antiretroviral regimen including a protease inhibitor was associated with a two-thirds reduction in risk of death (hazard ratio 0.33). The total reduction in death -- reflecting many treatment advances, not just antiretroviral therapy -- was more impressive: 5.3% mortality in 1996, 2.1% in 1997, 0.9% in 1998, and 0.7% in 1999. Both findings were highly statistically significant, p<0.001.

This study could not compare combinations including a protease inhibitor with combinations including an NNRTI (efavirenz, nevirapine, or delavirdine) because too few of the children were on NNRTI combinations -- only 3% in the last year of the study, 1999 -- compared to 73% on protease-inhibitor combinations, and 24% receiving only nucleoside analogs. But an accompanying editorial(2) noted that combination therapy with NNRTI drugs can achieve the same result. All the children were on antiretroviral therapy of some kind by 1999.

African American and Hispanic children were found to start therapy later. After statistical adjustment for severity of illness, this effect became less, and was no longer statistically significant. However, the authors suggested continued vigilance to ensure equitable access to treatment.

The authors also urged continued vigilance about the long- term risks of today's antiretroviral drugs when started in childhood; serious metabolic and other side effects have been seen in children as well as adults. This cohort study (PACTG 219) is continuing, and will be able to provide more information about long-term outcome and risk vs. benefit.

The accompanying editorial looked at treatment in developing countries. In the United States, the rate of HIV transmission from infected pregnant women to their children went from 25% to 1.4% with standard antiretroviral therapy; in those children who do get infected, beginning treatment in the first three months of life can stop viral replication completely and preserve normal immune function, provided proper treatment is continued. However, infrastructure in the developing world is just beginning to be created -- the United Nations AIDS Summit this year set a goal of only a 20% reduction in mother-to-child transmission by 2005. "Our efforts must focus on devising simple, relatively inexpensive, triple-combination regimens for the treatment of all HIV-1-infected pregnant women and all HIV-1-infected children. Such a regimen could be provided for $5 per day and would have a substantial effect on the prevention and treatment of HIV-1 disease in the developing world. These efforts would represent an important step toward changing the face of pediatric HIV-1 infection for the many millions who are affected by it around the world."(2)

References

1. Gortmaker SL, Hughes M, Cervia J, and others. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV- 1. THE NEW ENGLAND JOURNAL OF MEDICINE November 22, 2001; volume 345, number 21, pages 1522-1528.

2. Sullivan JL and Luzuriaga K. The Changing Face of Pediatric HIV-1 Infection. THE NEW ENGLAND JOURNAL OF MEDICINE November 22, 2001; volume 345, number 21, pages 1568-1569.

011123
ATN37403

Copyright © 2001 - AIDS Treatment News. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. Subscription lists are kept confidential. AIDS Treatment News, Subscription and Editorial Office: 1233 Locust St., 5th floor Philadelphia, PA 19107 800/TREAT-1-2 toll-free email: aidsnews@critpath.org  http://www.aidsnews.org

Subscription Information: Call 800/TREAT-1-2: Businesses, Institutions, Professionals: $270/year. Includes early delivery of an extra copy by email. Nonprofit organizations: $135/year. Includes early delivery of an extra copy by email. Individuals: $120/year, or $70 for six months. Special discount for persons with financial difficulties: $54/year, or $30 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2001. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1990, 2001. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Feedback/Contact Us.