Updated Guidelines for Antiretroviral Therapy—2005
Abstract and Commentary
By Dean L. Winslow, MD, FACP, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center, Clinical Professor of Medicine, Stanford University School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Dr. Winslow is a consultant for Bayer Diagnostics and Pfizer/Agouron, and is on the speaker’s bureau for Pfizer/Agouron.
Synopsis: The US Department of Health and Human Services (DHHS) periodically updates their guidelines for antiretroviral therapy. The latest iteration of these guidelines was published in October 2005. While continuing to emphasize triple drug antiretroviral regimens, a number of changes were made. These changes included since the previous DHHS Guidelines (published April 7, 2005) are summarized below.
Source: Panel on Clinical Practices for Treatment of HIV Infection, Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 6, 2005; www.AIDSinfo.nih.gov
What not to use as initial therapy: the panel recommends that a regimen containing ddI+tenofovir+NNRTI not be used as an initial regimen, due to reports of early virologic failure and rapid emergence of resistance mutations with this regimen, as well as a poor incremental CD4 response and, possibly, enhanced nucleoside-related toxicity due to a pharmacologic interaction between ddI and tenofovir. Also, while ritonavir-boosted tipranavir has been shown to be an important advance in treatment of patients who have developed virologic failure on other regimens, the panel does not recommend its use in treatment-naïve patients due to lack of clinical trial data in this setting.
Management of treatment experienced patients: This section of the Guidelines has been updated to redefine the goal of antiretroviral therapy in the management of treatment-experienced patients with virologic failure and reviews the role of more potent ritonavir-boosted protease inhibitors such as tipranavir with or without enfuvirtide. Table 23 clearly restates that the goal of antiretroviral therapy remains suppression of HIV viremia, but also now states that attempts to preserve some degree of immune response by using anti-retroviral drugs which by resistance testing only partial virologic suppression is anticipated, may be appropriate.
The following additional tables have been updated:
- Table 7 (Treatment Outcome of Selected Clinical Trials of Combination Antiretroviral Regimens in Treatment-Naïve Patients with 48-Week Follow-Up Data)-Outcome data with once daily abacavir/lamivudine and lopinavir/ritonavir have been added.
- Table 12 (Characteristics of Protease Inhibitors) was updated to include description of tipranavir and the option of once daily dosing of lopinavir/ritonavir in treatment naïve patients.
- Tables 16-21b (all pertain to toxicities) was updated with information about tipranavir including the black box warning relating to reports of clinical hepatitis and hepatic decompensation, and the recommendation to use this drug with caution in patients co-infected with hepatitis B or hepatitis C.
- Tables 23-25 (all pertain to management of virologic failure) have been updated and emphasize the importance of resistance testing in selecting a salvage regimen and, as expected, recommend regimens containing lopinavir/ritonavir, tipranavir/ritonavir as well as enfuvirtide. Structured treatment interruptions are discouraged as a management strategy.
- Table 26 (Suggested Minimum Target Trough Concentrations for Persons with Wild-type HIV-1) is updated with a suggested Cmin for atazanavir given as 150 ng/mL.
- Tables 28 and 29 (both pertain to use of antiretroviral agents in pregnant patients) update the USPHS perinatal antiretroviral guidelines and make reference to the use of tipranavir. (Animal teratogenicity studies have been essentially negative but since there has been little clinical experience or clinical trials of this agent in pregnancy, the guidelines conclude,". . . data are insufficient to recommend use during pregnancy.")
- Table 30 (Antiretroviral Agent Available Through Expanded Access Program) has been updated to include enrollment information for the Tibotec HIV protease inhibitor, TMC-114. This agent, like tipranavir, has shown good activity in clinical trials studying patients infected with PI-resistant HIV.
These updated guidelines have, as expected, grown quite voluminous (approximately 115 pages including appendices) as the number of available antiretroviral agents has increased over the last 18 years, and our experience in managing patients and using these agents has matured. The document is, over all, well referenced. These consensus guidelines present practical approaches to this important field of clinical practice.