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What's New in the Adult and Adolescent Antiretroviral Treatment Guidelines?
Revisions to the February 12, 2013, version of the guidelines include both a new section and key updates to existing sections. Significant updates are highlighted throughout the PDF version of the document.
New Section
Cost Considerations and Antiretroviral Therapy
- In the past, this guideline has not formally discussed costs related to antiretroviral therapy (ART). This new section provides an overview of costs as they relate to adherence, including discussion of cost-sharing, prior authorizations, and use of generic drugs. This section also elaborates on potential strategies for cost containment that do not compromise treatment effectiveness.
Key Updates to Existing Sections
The following are key updates to existing sections of the guidelines.
Change in Recommendations on Frequency of CD4 Count Monitoring
This change can be found in the “Laboratory Testing: HIV-RNA (Viral Load) and CD4 Count Monitoring ” section.
- The Panel emphasizes that viral load is the most important measure of response to ART, and should be monitored during therapy to assure consistent viral suppression. CD4+ T-lymphocyte cell count (CD4 count) measurement is essential when a patient enters into care, both to determine the urgency for ART initiation and the need for prophylaxis against opportunistic infections (OIs). After ART initiation, CD4 count monitoring is most helpful in patients with advanced HIV infection to guide the timing of discontinuation of OI prophylaxis or treatment.
- Frequent monitoring of CD4 counts, especially in those with higher counts (>300 cells/mm3) and consistently suppressed viral loads, is generally not required for patient management. Therefore, the Panel recommends the following frequency of CD4 monitoring in patients who have been on ART for at least 2 years with consistent viral suppression:
- CD4 count between 300–500 cells/mm3: CD4 count monitoring every 12 months (BII).
- CD4 count >500 cells/mm3: CD4 count monitoring is optional (CIII).
- The Panel recommends resumption of more frequent CD4 count monitoring in patients who experience virologic rebound; who develop new HIV-associated clinical symptoms; or who develop conditions or initiate therapy that may lead to reduction of CD4 cell count (AIII).
- The Panel also emphasizes that monitoring of lymphocyte subsets other than CD4 (e.g., CD8, CD19) is not clinically useful, is more expensive, and is not routinely recommended (BIII).
- A new table (Table 4) has been added to outline the Panel’s recommendations on the frequency of viral load and CD4 count monitoring. In addition, Table 3 has been updated to reflect these changes.
Change in Classification of Recommendations for Initial Treatment From “Preferred Regimens” to “Recommended Regimens”
This change can be found in the “What to Start: Initial Combination Regimens for the Antiretroviral-Naive Patient” section.
- In the past few years, the FDA has approved several new antiretroviral (ARV) agents and co-formulations for treatment-naive individuals. On the basis of data from long-term follow-up studies and experience in clinical practice, the Panel recognizes that options for initial therapy have expanded. Consequently, the Panel now refers to options for initial treatment as "Recommended" rather than "Preferred" regimens.
- Recommended regimens are further divided into two categories:
1. Regimens for ART-naive patients regardless of baseline viral load or CD4 cell count. These regimens include those previously termed “Preferred,” namely tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) with either efavirenz (EFV); ritonavir-boosted atazanavir (ATV/r) or darunavir (DRV/r); or raltegravir (RAL). In addition, 3 new regimens have been added to this category:
- Dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC): only for patients who are HLA-B*5701 negative
- DTG + TDF/FTC
- Elvitegravir (EVG)/cobicistat (cobi)/TDF/FTC: only for patients with pre-ART creatinine clearance ≥70 mL/min
2. Regimens that are also recommended, but only for patients with pre-ART plasma HIV RNA <100,000 copies/mL. These regimens include the following:
- EFV + ABC/3TC: only for patients who are HLA-B*5701 negative
- Rilpivirine (RPV)/TDF/FTC: only for patients with CD4 count >200 cells/mm3
- ATV/r + ABC/3TC: only for patients who are HLA-B*5701 negative
- The Panel has revised its list of Alternative Regimens (Table 6). Those listed as Alternative Regimens are effective and tolerable but, when compared with Recommended options, have potential disadvantages or fewer data supporting their use.
- Given the large number of Recommended and Alternative options, a number of ARV drugs are no longer recommended for initial therapy; these drugs include zidovudine (ZDV), nevirapine (NVP), unboosted ATV, ritonavir-boosted fosamprenavir (FPV/r) or saquinavir (SQV/r), and maraviroc (MVC).
- A new subsection has been added summarizing clinical trial data on antiretroviral strategies for initial therapy when ABC or TDF cannot be used.
Emphasis on Key Principles to Follow When Switching ARV Drugs in the Setting of Viral Suppression
The “Regimen Simplification” section of the previous guideline has been updated with a new title—“Regimen Switching in the Setting of Viral Suppression”—and includes the following key revisions.
- The Panel emphasizes that the key principle of regimen switch in this setting is to maintain viral suppression without compromising future options and that a patient’s prior treatment history and responses to ART, resistance profiles, and drug tolerance should be considered when contemplating a regimen switch.
- A new subsection has been added to discuss data from clinical trials investigating switching from traditional to alternative regimens.
Addition of a New Table That Provides Recommendations on ARV Drug Options When Switching ARV Drugs Because of Adverse Effects
- This new table has been added to the “Adverse Effects of Antiretroviral Agents” section to guide clinicians when it is necessary to switch ARV drugs because of adverse effects.
- In the introduction to this table, the Panel also emphasizes that the key principle of ARV switch in this situation is to maintain viral suppression without compromising future treatment options and that a patient’s prior treatment history and responses, resistance profiles, and drug tolerance should be considered when selecting a new ARV drug.
Additional Updates
Minor revisions have also been made to the following sections:
The most up-to-date versions of all the Clinical Guidelines can always be found at the Clinical Guidelines Portal, at the AIDSinfo web site.
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration
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