Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents

US Health & Human Services, December 1998

Introduction

These guidelines are intended for use by physicians and other health care providers who use antiretroviral therapy to treat HIV-infected adults and adolescents and serves as the companion document to the therapeutic principles formulated by the National Institutes of Health (NIH) Panel to Define Principles of Therapy of HIV Infection. The recommendations in this document are presented in the context of and with reference to the Principles of Therapy contained in the companion document. Together the documents should provide the pathogenesis-based rationale for therapeutic strategies as well as practical guidelines for implementing these strategies. While the guidelines represent the current state of knowledge regarding the use of antiretroviral agents, this is a rapidly evolving field of science, and the availability of new agents or new clinical data regarding the use of existing agents will result in changes in therapeutic options and preferences. Thus, in recognition of the need for frequent updates to this document, a subgroup of the Panel, the Antiretroviral Working Group, will meet monthly to review new data as it becomes available; recommendations for changes in this document will then be submitted to the Panel and incorporated as appropriate. Copies of this document and all updates are available from the HIV/AIDS Treatment Information Service (1-800-448-0440; TTY 1-888-480-3739; Fax 301-519-6616) and on the ATIS Web site (http://www.hivatis.org). They are also available from the National Prevention Information Network (NPIN) Web site (http://www.cdcnpin.org). These recommendations are not intended to substitute for the judgment of a physician who is an expert in the care of HIV-infected individuals. It is important to note that the Panel felt that where possible the treatment of HIV-infected patients should be directed by a physician with extensive experience in the care of these patients. When this is not possible, it is important to have access to such expertise through consultations.

Each recommendation is accompanied by a rating that includes a letter and a Roman numeral (Table I), similar to the rating schemes used in previous guidelines on the prophylaxis of opportunistic infections (Ols) issued by the U.S. Public Health Service and the Infectious Diseases Society of America^[1]. The letter indicates the strength of the recommendation, based on the opinion of the Panel, while the Roman numeral rating reflects the nature of the evidence for the recommendation (Table I). Thus, recommendations based on data from clinical trials with clinical endpoints are differentiated from those with laboratory endpoints such as CD4⁺ T lymphocyte count or plasma HIV RNA levels; where no clinical trial data are available, recommendations are based on the opinions of experts familiar with the relevant scientific literature. It should be noted that the majority of clinical trial data available to date regarding the use of antiretroviral agents have been obtained in trials enrolling predominantly young to middle-aged males. While current knowledge indicates that women may differ from men in the absorption, metabolism and clinical effects of certain pharmacologic agents, clinical experience and data available to date would suggest that there are no significant gender differences known that would modify these guidelines. However, theoretical concerns exist. The Panel urges continuation of the current efforts to enroll more women in antiretroviral clinical trials so that the data needed to re-evaluate this issue can be gathered expeditiously.

This document addresses the following issues: the use of testing for plasma HIV RNA levels (viral load) and CD4⁺ T cell count; considerations for when to initiate therapy in established HIV infection; special considerations for therapy in patients with advanced stage disease; interruption of therapy; considerations for changing therapy and available therapeutic options; the treatment of acute HIV infection; considerations for antiretroviral therapy in adolescents; and considerations for antiretroviral therapy in the pregnant woman.