The following changes have been made to several sections of the December 1, 2007
version of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents:

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 r
ecommended 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:

• “Antiretroviral components that are acceptable as initial antiretroviral components but are
  Inferior to preferred or alternative components”; and
• “Treatment outcome of selected clinical trials of combination antiretroviral regimens in treatment-naïve
  patients with 48-week follow-up data”.
   

The complete January 29, 2008 version of the adult treatment guidelines is available on the
aidsinfo web site at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. 

Changes will display highlighted in yellow.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration