clotet.qxp 4/2/09 11:38 am Page 52
HIV and AIDS
HIV Drug Resistance Testing
a report by
Roger Paredes
1
and Bonaventura Clotet
2
1. Physician, HIV Unit; 2. Head, HIV Unit, and Director, Retrovirology Laboratory, irsiCaixa Foundation, University Hospital Germans Trias i Pujol
The International AIDS Society-USA (IAS-USA) updated its resistance maintain viral suppression. All guidelines agree that HIV drug resistance
testing guidelines
1
in July 2008 to include the many recent additions to testing should be performed when HIV-infected persons enter into
the HIV armamentarium and increasing knowledge and understanding clinical care, whether or not they will be treated immediately. The goal
of HIV drug resistance. These changes include: the incorporation of of this strategy is to maximise the chances of detecting transmitted
new drug classes such as fusion inhibitors, CCR-5 antagonists and resistance. In addition, genotypic resistance testing is recommended for
integrase strand-transfer inhibitors; the increased complexity of all pregnant women prior to initiation of therapy and for those entering
antiretroviral therapy (ART), with the incorporation of new non- pregnancy with detectable HIV RNA levels while on therapy. In HIV-
nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g. etravirine) and infected individuals receiving antiretroviral therapy, resistance testing
protease inhibitors (PIs) (e.g. darunavir-ritonavir) retaining activity should be performed in the presence of virological failure. To ensure
against resistant virus; the need to address the biochemical correlates adequate performance of resistance testing, HIV-1 RNA levels should be
and clinical significance of antiretroviral drug resistance in non-B HIV- at least 1,000 copies/ml at the time of testing, although guidelines
1 strains, as ART programmes expand in resource-limited settings; the agree that resistance testing could be also attempted in individuals with
development of more sensitive techniques to detect drug resistance in HIV-1 RNA levels between 500 and 1,000 copies/ml. However, in this
minority variants; and the need to define a clinical role for viral tropism last group of patient the chances of amplifying HIV-1 sequences are
and replication capacity testing. All of these factors play key roles in markedly lower. Drug resistance testing might also be helpful when
the prevention and treatment of drug-resistant virus. managing suboptimal viral load reduction. However, this is less clear
because the addition of, or switch to, new antiretroviral drugs could be
The Department of Health and Human Services (DHHS) Panel on helpful to achieve viral suppression.
Antiretroviral Guidelines for Adults and Adolescents also included
recommendations for antiretroviral drug resistance testing in the last update Importantly, given that drug resistance mutations wane after treatment
of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected interruption, drug resistance testing in the setting of virological failure
Adults and Adolescents, published on 23 November 2008.
2
These guidelines should be performed while the patient is taking his/her antiretroviral drugs,
show high concordance with the latest IAS-USA guidelines regarding the or within four weeks after discontinuing therapy.
clinical indication of resistance testing (see Tables 1 and 2).
Because the CCR-5 antagonist maraviroc was incorporated into clinical
Clinical Indications of Resistance Testing practice during 2008, resistance testing guidelines address for the first time
The goal of resistance testing is to provide information to assist in the the clinical indications of tropism testing.
selection of the antiretroviral regimen(s) more likely achieve and
The US Food and Drug Administration (FDA) label and both the IAS-USA
and DHHS guidelines agree that co-receptor tropism assays should be
Roger Paredes is an Internal Medicine and Infectious
performed whenever the use of a CCR-5 inhibitor is being considered.
Diseases Physician at the HIV Unit of the University Hospital
Germans Trias i Pujol in Badalona and a Senior Researcher
In addition, co-receptor tropism testing might be considered for patients
in Molecular Virology at the Institut de Recerca de la SIDA. who exhibit virological failure on maraviroc (or any other CCR-5
His group develops translational research on epidemiology
antagonist) because virological failure to CCR-5 antagonists is frequently
and clinical aspects of HIV drug resistance, viral tropism and
the virology of HIV/AIDS vaccines. He is member of the
associated with a CCR-5 to CXCR-4 tropism switch. However, the
EuroHIVResistance Study Group and a virologist at the
practical applications of detecting such tropism change, are unclear at
Catalan HIV Vaccine Development Program (HIVACAT)
present. On one hand, there is only one CCR-5 antagonist available for
project for the development of an AIDS vaccine.
clinical use. Even if other CCR-5 antagonists become available, it is
unclear whether exposure to a new CCR-5 antagonist in subjects with
Bonaventura Clotet is Head of the HIV Unit and Director of
the Retrovirology laboratory irsiCaixa Foundation at the
previous CCR-5 antagonist failure would be an effective strategy, even
University Hospital Germans Trias i Pujol in Badalona. He is
if no tropism switch were detected after the first virological failure.
a member of the Drug Resistance Mutations Group of the
Finally, it is unknown whether the rates of virological suppression with a
International AIDS Society (IAS) and the Governing Council
of the IAS. Since 2006, Dr Clotet has been Co-director of the
salvage regimen not including a CCR-5 antagonist would be different
Catalan HIV Vaccine Development Program (HIVACAT)
depending on the viral tropism at the previous treatment failure.
project for the development of an AIDS vaccine.
E:
bclotet@irsicaixa.es
Given that that the emergence of X4 viruses is associated with
accelerated progression towards AIDS or death, co-receptor tropism
52 © TOUCH BRIEFINGS 2008
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