Wednesday, November 5, 2008

HIV/AIDS Update - Revised Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

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On November 3, 2008, the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents released a revised version of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.

The following changes have been made to the January 29, 2008 version of the guidelines. Key new updates are highlighted throughout the posted document (see below).

Format Changes

This revision is developed under a new format, whereby the relevant tables and references for each section are incorporated into the body of the document. Some larger tables are placed in an appendix at the end of the document. A separate PDF file with all the tables can be found at the AIDSinfo Web site.

Rating Changes
A new rating scheme is used in this guideline to be more consistent with other guidelines in infectious diseases. The changes are outlined below:

Strength of Recommendations
The D (should usually not be offered) and E (should never be offered) ratings have been removed. The A, B, and C ratings rate the strength of the statement. For example, an A rating for “not to initiate nevirapine in women with pre-treatment CD4 cell count >250 cells/mm3” indicates a strong recommendation to not initiate nevirapine in these patients.

Quality of Evidence

Previously, only randomized trials with clinical endpoints were given a I ranking. In this new rating scheme, a I ranking includes randomized trials with either clinical or validated laboratory outcomes (e.g., viral load). A II rating includes non-randomized trials or well-designed observational cohort studies with long term clinical outcomes. A III rating remains a recommendation based on expert opinion.

Content Changes
The key changes to the different sections of the guidelines are outlined below:

Laboratory Monitoring

  • A new table (Table 3) provides recommendations for laboratory tests to obtain at baseline and while receiving antiretroviral therapy to monitor for safety and treatment responses.
  • The Panel recommends that resistance testing be considered in patients with viral loads of 500–1,000 copies/mL but recognizes that it may not always be reliable at those levels (BII).

What to Start in Antiretroviral-Naïve Patients

Protease Inhibitor–Based Regimens:

  • Ritonavir-boosted darunavir has been added as a preferred PI component (AI).
  • Once-daily ritonavir-boosted lopinavir has been moved from alternative to preferred PI component (except for pregnant women) (AI).

Dual-NRTI Options:

  • Abacavir + lamivudine has been moved from a preferred to an alternative dual-NRTI component because of concerns regarding an increased risk of myocardial infarction in patients with high cardiac risk factors, as suggested by large observational cohort studies, and concerns regarding virologic potency in patients with baseline viral loads >100,000 copies/mL (BI).
Combinations Not to Use or to Use with Caution:
  • A combination of unboosted atazanavir + didanosine + emtricitabine (or lamivudine) is not recommended because of efficacy concerns (BI).
  • A combination of nevirapine + tenofovir + emtricitabine (or lamivudine) should be used with caution and with close monitoring of virologic responses because of reports of early virologic failure in several small studies (CII).

Management of Treatment-Experienced Patients

Regimen Simplification:
  • A new section on Regimen Simplification for virologically suppressed patients has been added to the discussion of Management of the Treatment-Experienced Patient.

Additional Updates
The following sections and their relevant tables have been updated:
  • Introduction
  • CD4+ T-cell count
  • Viral Load Testing
  • Coreceptor Tropism Assay
  • What Not to Use
  • Exposure Response and Therapeutic Drug Monitoring (and table for recommended antiretroviral drug concentrations)
  • HIV-Infected Adolescents
  • HIV-Infected Illicit Drug Users
  • HIV-Infected Women
  • Adherence to Antiretroviral Therapy (with a new table)
  • Antiretroviral-Associated Adverse Effects (and table for detection and management of adverse effects)
  • Antretroviral Drug Interactions (with a new format for interactions between antiretroviral and other drugs)
  • Tables describing the characteristics of antiretroviral drugs

The complete November 3, 2008 version of the adult treatment guidelines is available on the AIDSinfo web site at

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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