Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Revisions to the May 1, 2014, version of the guidelines include key updates to several existing sections and the addition of two new tables. Significant updates are highlighted throughout the document.

Key Updates

The following are key updates to existing sections of the guidelines.

What to Start: Initial Combination Regimens for the Antiretroviral-Naive Patient

Since the last version of these guidelines, data from clinical trials and cohort studies, as well as experience in clinical practice, have prompted significant changes to the list of Recommended, Alternative, and Other regimens for treatment-naive patients (Table 6). Additionally, a new table, titled “Antiretroviral (ARV) Regimen Considerations as Initial Therapy Based on Specific Clinical Scenarios,” has been created to guide clinicians on the selection of an initial ARV regimen based on specific clinical scenarios and ARV-related considerations (Table 7).

• There are now five Recommended regimens for antiretroviral therapy (ART)-naive patients—four integrase strand transfer inhibitor (INSTI)-based regimens and one ritonavir-boosted protease inhibitor (PI/r)-based regimen, as listed below:

INSTI-Based Regimens:

• Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC)—only for patients who are HLA-B*5701 negative (AI)
• DTG plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (AI)
• Elvitegravir/cobicistat/TDF/FTC (EVG/c/TDF/FTC)—only for patients with pre-ART CrCl >70 mL/min (AI)
• Raltegravir (RAL) plus TDF/FTC (AI)

PI/r-Based Regimen:
• Darunavir/ritonavir (DRV/r) plus TDF/FTC (AI)

• Two regimens previously classified as Recommended regimens have been moved to the Alternative regimens category, with the rationale stated below:
• Atazanavir/ritonavir (ATV/r) plus TDF/FTC (BI)—Based on the results of a large comparative clinical trial showing a greater rate of discontinuation with ATV/r plus TDF/FTC because of toxicities when compared to (DRV/r or RAL) plus TDF/FTC
• Efavirenz/TDF/FTC (EFV/TDF/FTC) (BI)—Based on concerns about the tolerability of EFV in clinical trials and practice, especially the high rate of central nervous system (CNS)-related toxicities and a possible association with suicidality
• Three regimens (ATV/r plus ABC/3TC, EFV plus ABC/3TC, and rilpivirine/TDF/FTC) that were previously listed as Recommended regimens for baseline HIV RNA <100,000 copies/mL or CD4 T lymphocyte (CD4) count >200 cells/mm3 are now in the Alternative or Other category, with the same caveat about limiting their use in these populations.
• Two regimens that use fewer than two nucleoside reverse transcriptase inhibitors (DRV/r plus RAL and lopinavir/ritonavir plus 3TC) are now listed among the Other regimens, with the caveat that their use would be limited to those patients who cannot take either TDF or ABC.
• Coformulations of atazanavir (ATV) and darunavir (DRV) with the pharmacokinetic (PK) enhancer cobicistat (COBI) have been added to the Alternative regimen options.

Virologic Failure

The following key updates have been made to this section:

• The Management of Virologic Failure in Different Clinical Scenarios subsection has been expanded to provide guidance on the management of patients failing first and second ART regimens.
• A new subsection on Isolated CNS Virologic Failure and New OnsetNeurologic Symptoms has been added.
• The Suboptimal Immunologic Response Despite Viral Suppression subsection has been moved from this section to become a stand-alone section (see below). 

Poor CD4 Cell Recovery and Persistent Inflammation Despite Viral Suppression

• This new section describes the role of persistently low CD4 cell count (<200 cells/mm3) and persistent inflammation/immune activation on the increased risk of AIDS- and non-AIDS-related morbidity.
• The Panel emphasizes that currently no therapeutic intervention designed to improve CD4 cell recovery or immune activation has been proven to improve health.

Acute/Early HIV Infection

• This section has been updated to include the 2014 Centers for Disease Control and Prevention’s recommendation for diagnosis of HIV infection, including in individuals with acute/early HIV infection.

HIV-2 Infection

• This section has been updated with the most recent literature on ARV use in HIV-2-infected patients.

HIV/Hepatitis C Virus (HCV) Coinfection

• The text and table (Table 12) in this section have been updated with information on the concomitant use of different ARV drugs with the new HCV drug combination of ombitasvir, paritaprevir, ritonavir, and dasabuvir.

Drug Interaction

• The text of this section has been updated to focus on mechanisms of interaction of ARV drugs.
• A new table, titled “Mechanisms of Antiretroviral Associated Drug Interactions,” has been developed to provide clinicians with information on clinically relevant mechanisms of PK-associated interactions for individual ARV drugs (Table 17).
• All the Drug Interaction tables have been updated; in particular, interactions related to ATV/c, DRV/c, and EVG plus PI/r have been added to these tables (see Tables 19a–e, 20a, and 20b).

Additional Updates

Minor revisions have also been made to the following sections:

• Discontinuation or Interruption of Antiretroviral Therapy
• Exposure-Response Relationship and Therapeutic Drug Monitoring (TDM) for Antiretroviral Agents
• Monthly Average Wholesale Price of Antiretroviral Drugs (Table 16)
• Drug Characteristics tables (Appendix B, Tables 1–7)

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資料轉載來源：What's New in the Guidelines? | Adult and Adolescent ARV Guidelines | AIDSinfo