International AIDS Society-USA Guidelines Recommend Starting Antiretroviral
Therapy at 500
Coinciding with the XVIII International AIDS Conference (AIDS
2010) this week in Vienna, the International AIDS Society-USA
(IAS-USA) has released new antiretroviral therapy (ART) guidelines
for adults with HIV. The updated guidelines, published in
21, 2010 Journal of the American Medical Association (JAMA)
concur with the current U.S. Department of Health and Human
Services recommendations, which advise that asymptomatic people
should initiate ART when their CD4 T-cell count falls to 500
cells/mm3. But there is no CD4 count upper limit for starting
treatment, and the expert panel recommended therapy for certain
groups regardless of CD4 cell level. However, they emphasized,
it is important to assess individual readiness before starting
who should consider ART at all CD4 counts, according to the IAS panel,
include pregnant women, people over age 60, and those with co-existing
conditions such as hepatitis B or C coinfection, HIV-associated kidney
disease or elevated cardiovascular disease risk.
treatment early may help prevent inflammation and other adverse consequences
of chronic HIV infection, and beginning therapy during primary or acute
infection may help keep the viral set-point low. Under certain circumstances,
the guidelines panel added, ART may be used to reduce the risk of HIV
is the text of a JAMA announcement summarizing the revised guidelines.
The full recommendations are available for free online at http://jama.ama-assn.org/cgi/content/full/304/3/321.
Treatment Guidelines Indicate Importance of Early,
Individualized Antiretroviral Treatment
Austria -- July 18, 2010 -- Advances in antiretroviral treatment (ART)
have shown that the progressive immune system destruction caused by
HIV infection, including AIDS, can be prevented, indicating the importance
of beginning ART early, when a person with HIV infection is without
symptoms, according to the 2010 recommendations of the International
AIDS Society-USA Panel, published in the July 21 issue of JAMA,
a theme issue on HIV/AIDS. This shift to earlier therapy is made possible
by the increased understanding of the negative consequences of ongoing
HIV replication and the development of newer drugs providing the potential
for potent viral suppression in initial and subsequent therapy.
Melanie A. Thompson, MD, of the AIDS Research Consortium of Atlanta
and chair of the International AIDS Society-USA Antiretroviral Therapy
Guidelines Panel, presented the recommendations of the panel at a JAMA
media briefing at the International AIDS Conference in Vienna.
"Successful ART is associated with dramatic decreases in AIDS-defining
conditions and their associated mortality. Expansion of treatment options
and evolving knowledge require revision of guidelines for the initiation
and long-term management of ART in adults with HIV infection,"
the authors write. Since the 2008 International AIDS Society-USA ART
guidelines, new data have emerged regarding timing of therapy, optimal
regimen choices, monitoring, and newer drugs are better understood in
terms of efficacy, toxicity, and potential uses in HIV management. New
relevant HIV data and research since 2008 was reviewed by the panel
for the 2010 recommendations
When to Start
"The prominence of non-AIDS events as a major cause of morbidity
and mortality in those with ongoing HIV replication suggests that early
ART initiation may further improve the quality and length of life for
persons living with HIV," the authors write. They add that patient
readiness for treatment is a key consideration when deciding when to
initiate ART. There is no CD4+ cell count threshold at which initiating
therapy is contraindicated. Initiation of therapy is recommended for
asymptomatic individuals with CD4+ cell counts at 500 [cells/mm3] or
below. Treatment should be considered for asymptomatic individuals with
CD4+ cell counts greater than 500 [cells/mm3] and is recommended regardless
of CD4+ cell count for patients with symptomatic established HIV disease.
Therapy is also recommended for patients with other conditions such
as pregnancy, age older than 60 years, hepatitis B or C virus coinfections,
HIV-associated kidney disease, active or high risk for cardiovascular
disease, opportunistic diseases, symptomatic primary HIV infection,
and situations in which there is high risk for HIV transmission such
as serodiscordant (one HIV-infected and one HIV-uninfected) partners.
Once initiated, ART should be continued, except in the context of a
clinical trial. Risk reduction counseling should be a routine part of
care at each patient-clinician interaction.
What to Start
According to the authors, components of the initial and subsequent regimens
must be individualized, particularly in the context of concurrent (occurring
at the same time) conditions. Fixed-dose combinations are recommended
when possible for convenience. Tenofovir
plus emtricitabine [Truvada] is the recommended NRTI (nucleoside
or nucleotide analogue reverse transcriptase inhibitor) combination
in initial therapy. Zidovudine
plus lamivudine [Combivir] should be reserved for instances in which
neither tenofovir nor abacavir [Ziagen, also in the Epzicom
and Trizivir combinations]
can be used. The recommended third component should be efavirenz
[Sustiva] or a ritonavir-boosted protease inhibitor (particularly
or darunavir [Prezista])
or the integrase inhibitor raltegravir
[Isentress]. Three or 4 NRTIs alone are not recommended for initial
therapy. There are also considerations for initial therapy in patients
with specific conditions.
Plasma HIV-1 RNA levels should be monitored frequently when treatment
is initiated or changed for virologic failure until viral load decreases
below detection limits and regularly thereafter, the authors write.
Once the viral load is suppressed for a year and CD4+ cell counts are
stable at 350 [cells/mm3] or greater, viral load and CD4+ cell counts
can be monitored at intervals up to 6 months in patients with dependable
adherence. Baseline genotypic testing for resistance should be performed
in all patients who have not received treatment before and in cases
of confirmed virologic failure. The goal of therapy, even in heavily
pre-treated patients, should be HIV-1 RNA suppression below commercially
available assay quantification limits.
When to Change and What To Change To
According to the authors, maintenance of regimen potency is the objective
when switching ART regimens. Virologic failure of an initial regimen
(confirmed measurable viremia [presence of the virus in the blood stream])
should be identified and treated as early as possible with at least
2 (and ideally 3) fully active drugs to avoid the accumulation of resistance
mutations. Depending on the resistance profile and options available,
inclusion of agents from new drug classes should be considered. Monotherapy
with a ritonavir-boosted protease inhibitor should be avoided unless
other drugs cannot be considered for reasons of toxicity or tolerability.
Design of a new regimen should consider previous drug exposure, previous
and current resistance profile, drug interactions, and history of intolerance
or toxicity. Treatment interruptions should be avoided, except in the
context of controlled clinical trials.
far too many HIV-infected persons present for medical care
with advanced disease, both in wealthy and resource-limited settings.
Universal voluntary HIV testing, comprehensive prevention services,
and early linkage to care and treatment are necessary to ensure that
advances in ART are made available during earlier disease stages. Advances
in ART have shown that AIDS, as traditionally defined, can be prevented.
One of the greatest challenges is that full implementation of these
guidelines will require addressing social and structural barriers to
diagnosis and care, as well as the pervasive stigma and discrimination
associated with an HIV diagnosis," the authors conclude.
Panel affiliations: AIDS Research Consortium of Atlanta, Atlanta,
GA; University of California San Diego, La Jolla, CA; New York University
School of Medicine, New York, NY; Hospital Juan Fernandez/University
of Buenos Aires Medical School and Fundacion Huesped, Argentina; Hospital
Clinic-IDIBAPS, University of Barcelona, Spain; University Hospital
Zurich, Division of Infectious Diseases and Hospital Epidemiology, University
of Zurich, Switzerland; Columbia University College of Physicians and
Surgeons, New York, NY; Harvard Medical School, Boston, MA; International
AIDS Society-USA, San Francisco, CA; BC-Centre for Excellence in HIV/AIDS,
Providence Health Care and University of British Columbia, Vancouver,
Canada; Academic Medical Center, University of Amsterdam, Netherlands;
University of California San Diego and Veterans Affairs San Diego Healthcare
System, San Diego, CA; Luigi Sacco Hospital, Milan, Italy; University
Hospital of Lausanne, Switzerland; University of California San Francisco
and San Francisco Veterans Affairs Medical Center, San Francisco, CA;
Hôpital Bichat-Claude Bernard and Xavier Bichat Medical School,
Thompson, JA Aberg, P Cahn, and others. Antiretroviral Treatment of
Adult HIV Infection: 2010 Recommendations of the International AIDS
Society-USA Panel. JAMA 304(3): 321-333 (Free full text[http://jama.ama-assn.org/cgi/content/short/304/3/321]).
July 21, 2010.
and Archives Journals. New HIV Treatment Guidelines Indicate Importance
of Early, Individualized Antiretroviral Treatment. Press release. July