Antiretroviral Therapy Guidelines Updated, but No Major Changes
previous revision of the guidelines in December
2009 shifted the recommended threshold for initiating ART
from 350 to 500 cells/mm3; half of the panel issuing the guidelines
thought treatment should be started even sooner. The latest
update, however, does not make any changes with regard to when
to start treatment.
On January 10, 2011, the U.S.
Department of Health and Human Services (DHHS) announced
the latest revision of its Guidelines for the
Use of Antiretroviral Agents in HIV-1-Infected Adults
and Adolescents. The recent update does not
introduce major changes related to when to start
antiretroviral therapy (ART) or what drugs to use,
but it includes new recommendations related to CD4
cell count and viral load testing, as well treatment
of HIV positive people with hepatitis B or tuberculosis
CCR5 antagonist maraviroc
(Selzentry) plus zidovudine/lamivudine
(Combivir) was added as an "acceptable" option
for first-line therapy; other NRTI backbones have not yet
been adequately studied with maraviroc. But boosted saquinavir
(Invirase) was downgraded -- from "alternative"
to "acceptable but should be used with caution"
-- due to the potential for heart rhythm disturbances.
regard to monitoring, the DHHS panel now recommends that people
on ART with a high CD4 cell count and no other health issues
can generally get their T-cells measured less often, every
6-12 months. They also said that since viral load "blips"
-- or transient, low-level increases -- are common, changes
should only be considered a reflection of treatment failure
only if confirmed above 200 copies/mL.
to coinfections, the panel offered more specific advice for
treatment of HIV/HBV coinfection,
especially for people who are resistant to or unable to take
also in the Truvada
coformulations). And based on the latest research, they now
recommend that all HIV positive patients with tuberculosis
should receive ART, generally within 2-4 weeks, but at least
within 8 weeks of starting TB treatment.
The full revised guidelines are available
Below is the text of the introductory
section explaining the latest changes in more detail. Letters
and numbers following each point indicate the strength of
the recommendation and quality of evidence, with "AI"
New in the Guidelines?
changes made to update the December 1, 2009, version of
the guidelines are summarized below. Throughout the revised
guidelines, significant updates are highlighted and fully
The Panel emphasizes its recognition of the importance of
clinical research in generating evidence to address unanswered
questions related to the optimal safety and efficacy of
antiretroviral therapy (ART). The Panel encourages both
the development of protocols and patient participation in
well-designed, Institutional Review Board (IRB)-approved
CD4 T-Cell Count
The Panel recognizes that changes in CD4 cell count are
seldom used in decision for ART changes in a patient on
a suppressive ART regimen whose CD4 count is well above
the threshold for opportunistic infection risk. In such
patients, the Panel recommends that the CD4 count may be
monitored less frequently, for example every 6 to 12 months
(instead of every 3 to 6 months), unless there are changes
in the patient's clinical status, such as new HIV-associated
clinical symptoms or initiation of treatment with interferon,
corticosteroids, or anti-neoplastic [anti-cancer] agents
Viral Load Testing
The Panel recognizes that low-level positive viral load
results (typically < 200 copies/mL) have been commonly
reported with some viral load assays. For the purpose of
patient monitoring, the Panel defines virologic failure
as a confirmed viral load > 200 copies/mL, which eliminates
most cases of viremia caused by isolated blips or assay
The Panel provides more specific recommendations on when
to use genotypic testing to detect resistance to integrase
strand transfer inhibitors (INSTIs).
standard genotypic drug-resistance testing involves
testing for mutations in the reverse transcriptase (RT)
and protease (PR) genes, if transmitted INSTI resistance
is a concern, providers may wish to supplement standard
genotypic resistance testing with genotypic testing
for resistance to this class of drugs (CIII).
persons failing INSTI-based regimens, genotypic testing
for INSTI resistance should be considered to determine
whether to include a drug from this class in subsequent
to Start: Initial Combination Regimens for the Antiretroviral-Naive
Changes to the "What to Start" recommendations
include the following:
regimen consisting of maraviroc (MVC) + zidovudine/lamivudine
(ZDV/3TC) is now listed as an "Acceptable Regimen"
because FDA approval of MVC for use in ART-naive patients
was based on the results of a randomized controlled
trial using this regimen (CI).
+ tenofovir/emtricitabine (TDF/FTC)" and "MVC
+ abacavir (ABC)/3TC" have been added as "Regimens
that may be acceptable but more definitive data are
response to a recent change to the Invirase product
label based on findings from a healthy volunteer study
that reported significant PR and QT interval prolongations,
ritonavir-boosted saquinavir (SQV/r)-based regimens
have been moved from "Alternative PI-based Regimens"
to "Regimens that are Acceptable but Should be
Used with Caution."
B (HBV)/HIV Coinfection
This section has been revised to provide more specific recommendations
for management of HIV patients coinfected with HBV, including
recommendations for patients with 3TC/FTC-resistant HBV
infection [the two drugs in Truvada] and for patients who
cannot tolerate TDF [tenofovir]-based regimens.
Mycobacterium Tuberculosis Disease
With HIV Coinfection
Based on recent randomized controlled trials showing survival
and clinical benefits of starting ART earlier in treatment-naive
patients with active tuberculosis (TB) disease, the Panel
provides the following recommendations on when to start
ART in patients who are receiving treatment for active TB
but are not yet on ART.
HIV-infected patients with diagnosed active TB should
be treated with ART (AI).
patients with CD4 count < 200 cells/mm3, ART should
be initiated within 2-4 weeks of starting TB treatment
patients with CD4 count 200-500 cells/mm3, the Panel
recommends initiating ART within 2-4 weeks, or at least
by 8 weeks after commencement of TB therapy (AIII).
patients with CD4 count > 500 cells/mm3, most panel
members also recommend starting ART within 8 weeks of
TB therapy (BIII).
Effects of Antiretroviral Agents
A new table format provides clinicians with a list of the
most common and/or severe known antiretroviral (ARV)-associated
adverse events listed by ARV drug class.
The following sections and their relevant tables have also
Antiretroviral Therapy in Treatment-Naive Patients
Not to Use
and Immunologic Failure (previously titled "Management
of Patients with Antiretroviral Treatment Failure")
Relationship and Therapeutic Drug Monitoring for Antiretroviral
and Illicit Drug Users (with new Table)
Interactions (and Tables)
Characteristics Tables (Appendices)
Panel on Antiretroviral Guidelines for Adults and Adolescents.
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected
Adults and Adolescents. January 10, 2011.
R Klein and K Struble. Revised Adult HIV Treatment Guidelines
available. HIV/AIDS Update. January 10, 2011.
U.S. DHHS. Updated DHHS Adult and Adolescent Antiretroviral
Treatment Guidelines Now Available. AIDSinfo At-A-Glance 7(2).
January 10, 2011.