Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents January 29, 2008 Developed by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC) How to Cite the Adult and Adolescent Guidelines: Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 29, 2008; 1-128. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed (insert date) [insert page number, table number, etc. if applicable] It is emphasized that concepts relevant to HIV management evolve rapidly. The Panel has a mechanism to update recommendations on a regular basis, and the most recent information is available on the AIDSinfo Web site (http://AIDSinfo.nih.gov). January 29, 2008 What’s New in the Document? The following changes have been made to several sections of the December 1, 2007 version of the guidelines. What to Start: Initial Combination Regimens for the Antiretroviral-Naïve Patient? The Panel revised its recommendations for several “preferred” and “alternative” antiretroviral components for treatment-naïve patients: “Abacavir + lamivudine” has been changed from “alternative” to “preferred” 2-NRTI component in patients who have tested negative for HLA-B*5701 (AII). “Zidovudine + lamivudine” has been changed from “preferred” to “alternative” 2-NRTI component (BII). “Ritonavir-boosted saquinavir” has been changed from a PI-option that was considered as “Acceptable as initial antiretroviral components but inferior to preferred or alternative components” to an “alternative” PI component (BII). The following options are no longer recommended as components for initial therapy in treatment-naïve patients: o Nelfinavir as PI component o Stavudine + lamivudine as 2-NRTI components o Abacavir + zidovudine + lamivudine as a triple-NRTI combination regimen A new topic entitled “Other Treatment Options Under Investigation: Insufficient Data to Recommend” has been added, which includes a review of recent clinical trial data in treatment-naïve patients for ritonavir-boosted darunavir- based regimens, maraviroc-based regimens, and raltegravir-based regimens. Treatment Interruption This section has been updated with recent data on short-term and long-term treatment interruption. The Panel reaffirms our recommendation that aside from unplanned or planned short-term interruption due to illnesses precluding oral therapy or toxicities, long-term treatment interruption is not recommended unless in the context of a clinical trial (DI). Acute HIV Infection • A new table on “Identifying, diagnosing, and managing acute HIV-1 infection” has replaced the table on “Associated signs and symptoms of acute retroviral syndrome and percentage of expected frequency”. • The Panel also recommends that since clinically significant resistance to PIs is less common than resistance to NNRTIs in antiretroviral-naïve persons who harbor drug resistant virus, if therapy is initiated before drug resistance test results are available, consideration should be given to using a PI-based regimen (BIII). Mycobacterium Tuberculosis Disease or Latent Tuberculosis Infection with HIV Coinfection This section has been updated with the following information: • Discussions and recommendations on the timing of initiation of antiretroviral therapy in patients with active tuberculosis (TB), with emphasis on the risks and benefits of concomitant therapy related to overlapping toxicities, drug interactions, CD4 cell counts, and potential for immune reconstitution inflammatory syndrome. • Recommendation for repeat testing to detect latent TB infection in persons who had CD4 count <200 cells/mm3 and have tested negative prior to antiretroviral therapy and have improved CD4 count to >200 cells/mm3 (BII). Table Updates: • Various tables have been updated to include information regarding etravirine, updates on various antiretroviral drugs, as well as new atazanavir dosing recommendations when used in combination with proton pump inhibitors or H2 receptor antagonists. • The following tables have been removed from the document: o “Antiretroviral components that are acceptable as initial antiretroviral components but are inferior to preferred or alternative components”; and o “Treatment outcome of selected clinical trials of combination antiretroviral regimens in treatment-naïve patients with 48-week follow-up data”. January 29, 2008 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page i January 29, 2008 Table of Contents Guidelines Panel Roster ............................................................................................................................... v INTRODUCTION .......................................................................................................................................... 1 Key Clinical Questions Addressed by Guidelines ..................................................................... 1 Guidelines Process ..................................................................................................................................... 1 BASELINE EVALUATION ...................................................................................................................... 3 LABORATORY TESTING FOR INITIAL ASSESSMENT AND MONITORING FOR THERAPEUTIC RESPONSE .................................................................................................. 4 CD4 T-Cell Count ..................................................................................................................................... 4 Viral Load Testing .................................................................................................................................... 4 Drug Resistance Testing ........................................................................................................................ 5 Genotypic and Phenotypic Resistance Assays .................................................................. 5 Use of Resistance Assays in Clinical Practice ................................................................. 6 HLA-B*5701 Screening ............................................................................................................................ 7 Coreceptor Tropism Assays..................................................................................................................... 8 TREATMENT GOALS.................................................................................................................................. 10 Strategies to Achieve Treatment Goals.............................................................................................. 10 WHEN TO START: Indications for Initiation of Antiretroviral Therapy ........................... 12 WHAT TO START: Initial Combination Regimens for the Antiretroviral-Naïve Patient ........................................................................................................... 16 Considerations When Selecting a First Antiretroviral Regimen for Treatment-Naïve Patients................................................................................................................. 16 NNRTI–Based Regimens (1 NNRTI + 2 NRTIs) ...................................................................... 17 Summary: NNRTI-Based Regimens ........................................................................................ 17 PI-Based Regimens (Ritonavir-Boosted or Unboosted PIs + 2 NRTIs) ........................ 19 Summary: PI-Based Regimens ................................................................................................ 19 Dual-Nucleoside Options as Part of Initial Combination Therapy....................................... 22 All-NRTI Regimens ................................................................................................................................ 24 Other Treatment Options Under Investigation: Insufficient Data to Recommend ... 24 WHAT NOT TO USE ................................................................................................................................. 26 Antiretroviral Regimens Not Recommended .............................................................................. 26 Antiretroviral Components Not Recommended ........................................................................ 26 LIMITATIONS TO TREATMENT SAFETY AND EFFICACY ......................................... 28 Adherence to Antiretroviral Therapy .............................................................................................. 28 Adverse Effects of Antiretroviral Agents ....................................................................................... 28 Drug Interactions ........................................................................................................................................ 29 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page ii January 29, 2008 MANAGEMENT OF THE TREATMENT–EXPERIENCED PATIENT ........................ 32 The Treatment-Experienced Patient ................................................................................................ 32 Definitions and Causes of Antiretroviral Treatment Failure ................................................ 32 Assessment of Antiretroviral Treatment Failure and Changing