An updated version of the Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, which includes revised recommendations for when to initiate anti-HIV therapy, will be posted to the HIV/AIDS Treatment Information Service (ATIS) Web site (http://www.hivatis.org) at 9:00 a.m. ET on Feb. 5, 2001.
The Guidelines were developed by the Panel on Clinical Practices for the Treatment of HIV Infection, a joint effort of the Department of Health and Human Services and the Henry J. Kaiser Family Foundation. Initially published in 1998, the Guidelines were constructed as a "living document" and are updated by the Panel as new data emerge.
"Although antiretroviral therapy has provided extraordinary benefits to many patients, we know that we cannot eradicate HIV infection with currently available medications," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID) and co-chair of the Panel. "We also recognize that serious toxicities are associated with the long-term use of antiretroviral drugs. The new treatment guidelines provide patients and their doctors with evidence-based recommendations for initiating antiretroviral therapy that take into account both the benefits and potential risks of currently available treatment regimens."
The new Guidelines recommend considering starting antiretroviral therapy when an asymptomatic HIV-infected person's CD4+ T-cell count falls below 350 cells per cubic millimeter (mm3); previous Guidelines recommended consideration of therapy for asymptomatic patients with a CD4+ T-cell count lower than 500 cells/mm3.
For asymptomatic HIV-infected patients with CD4+ T-cell counts higher than 350 cells/mm3, treatment should be considered when the level of HIV in plasma is high [more than 30,000 copies per milliliter (ml) when using the branched DNA test, or more than 55,000 copies/ml when using the RT-PCR test]; previous Guidelines recommended consideration of therapy at lower levels of plasma HIV (10,000 copies/ml measured by branched DNA, or 20,000 copies/ml measured by RT-PCR). The Guidelines continue to recommend antiretroviral therapy for all patients with the acute HIV syndrome, those within six months of HIV seroconversion, and all patients with symptoms ascribed to HIV infection.
The Panel stresses that the Guidelines should be considered as a tool to help patients and their physicians make individual treatment decisions based on the best available information, but that much remains to be learned about how best to treat HIV-infected individuals.
"The updated Guidelines recognize that we do not yet have the data we need to make definitive recommendations about the optimal time to start treatment," says John G. Bartlett, M.D., chief of the division of infectious diseases at the Johns Hopkins University Medical Center and co-chair of the Panel. "We highlight the uncertainty, allow for flexibility, encourage an individualized approach to treatment, and, at the same time, try to provide guidance."
The Guidelines also include new drug-specific recommendations. Two new entries are included in the "strongly recommended" category of anti-HIV drug treatments. One of these is the recently approved protease inhibitor Kaletra, which is a co-formulation of ritonavir (approved in 1996) and lopinavir. The other new entry is the combination of ritonavir and indinavir (another protease inhibitor approved in 1996). These treatment options take advantage of the ability of ritonavir to boost the levels of other protease inhibitors, creating a potent anti-HIV combination. The protease inhibitor combinations are used along with combinations of certain nucleoside analogue reverse transcriptase inhibitors, which represent the "backbone" of anti-HIV treatments.
Also in the revised Guidelines is a section on the importance of adherence to therapy. "Extraordinarily high rates of adherence to an antiviral drug regimen are necessary to maintain control over HIV replication," says Dr. Bartlett. "HIV is very unforgiving in this regard. It is impossible to over-emphasize the importance of maximizing adherence once the decision is made to begin therapy."
Another important addition to the Guidelines is an updated section on the expanding scope of antiretroviral drug toxicities. "We are very concerned about a number of toxicities associated with the long-term use of antiretroviral drugs," says Dr. Fauci. "Particularly alarming is the alteration of fat metabolism that can emerge during treatment. We are seeing an increasing number of patients with dangerously high levels of cholesterol and triglycerides. The good news is that new anti-HIV treatments have dramatically improved the quality of life for many patients, and the incidence of AIDS and AIDS-related deaths has dramatically decreased. The bad news is that we now must find ways to deal with unanticipated toxicities, including the potential for premature coronary disease."
The updated Guidelines are available at http://www.hivatis.org in two formats, a typeset version (PDF) and a Web version (HTML). Single copies can be ordered by calling 1-800-448-0440 (international callers may call 1-301-519-0459), or by sending an e-mail request to firstname.lastname@example.org.
Co-conveners of the Panel on Clinical Practices for the Treatment of HIV Infection are Eric Goosby, M.D., on behalf of the Department of Health and Human Services, and Jennifer Kates, M.A, M.P.A., on behalf of the Henry J. Kaiser Family Foundation. Oren J. Cohen, M.D., NIAID Assistant Director for Medical Affairs, serves as the Panel's Executive Secretary.
NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
The Henry J. Kaiser Family Foundation, based in Menlo Park, Calif., is an independent philanthropy focusing on the major health care issues facing the nation. The Foundation is not associated with Kaiser Permanente or Kaiser Industries.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov. HIV-related information is also available on the Kaiser Family Foundation Web site at http://www.kff.org/sections.cgi?section=hivaids.