International AIDS Society Newsletter, no. 21

IAS1
INTERNATIONAL
AIDS SOCIETY
The Global HIV Drug Resistance Surveillance Program:
a Partnership between WHO and IAS
Diane Havlir, MD, Division of Infectious Diseases, University of California, San Diego
150 W Washington Street, Suite 100, San Diego, CA 92103, USA, Stefano Vella, MD, Istituto Superiore Di Sanita, Laboratory of
Virology - Div of Antiviral Therapy, Viale Regina Elena 299, IT-00161 Rome, Italy and Scott Hammer, MD, Division of Infectious
Diseases, Columbia University, 630 West 168th Street, New York, NY 10032, USA

The World Health Organization (WHO) in
conjunction with the International AIDS
Society (IAS) is developing a Global HIV Drug
Resistance Surveillance Program. One of the
principal goals of this ambitious effort is to
provide surveillance information on antiretroviral drug resistance to help guide national and
international antiretroviral treatment programs and guidelines. Through a dynamic and
collaborative global network of institutions,
laboratories and investigators, the program
will assess the geographic and temporal HIV
drug resistance patterns in persons in need or
already treated with antiretroviral (ARV) therapy (ART). Information will be disseminated
rapidly in order to inform policy makers and
program managers. HIV drug resistance surveillance information will also bring an
increased understanding of the determinants of
drug resistance and will identify ways to minimize its appearance, evolution and spread.
Rationale for WHO/IAS Surveillance Program
There is an urgent need for a Global HIV Drug
Resistance Surveillance Program. The WHO
estimates that among the 40 million people
infected with HIV, there are at least 5.8 million individuals in need of ART. There is a
global effort with increasing momentum supported by The Global Fund to Fight AIDS,
Tuberculosis and Malaria, WHO, UNAIDS,
UNICEF, Medecins-Sans-Frontieres and private sector underway to rapidly increase access
to ART in resourcelimited settings. The
Commission on Macroeconomics and Health
proposes a target coverage of antiretroviral use
of 45% to those in need by the year 2007. To
maximize the effectiveness of initial antiretro
viral therapy and to optimize the durability of
available regimens, surveillance information
on drug resistance will be essential. The WHO
recently released interim guidelines designed
to provide guidance to resource limited countries anticipating the incorporation of ART
into their health care system (1). These guidelines make every effort to minimize drug resistance by advocating triple drug regimens that
effectively suppress viral replication and by
stressing adherence to ARV regimens.
Nonetheless, it is an inevitable consequence
that drug resistance will occur with the wider
dissemination of ARV.
The information and data base generated in
the HIV Global Drug Resistance Monitoring
Program will prove an invaluable resource to
public health officials, governments, clinicians, researchers, and industry. Access to this
information will allow public health bodies to
monitor trends in drug resistance and target
education and intervention programs in areas
with increasing rates or high prevalences of
drug resistance. A rational approach for
resource allocation for purchase of antiretroviral agents by governments and the private sector requires knowledge of emerging drug resistance patterns. Treatment guidelines for HIV
are a necessary component of containment of
drug resistance and are based on either knowledge or assumptions of patterns of drug resistance in the community. Both models of
empiric treatment based on known susceptibility patterns or individualized treatment
based on drug resistance testing will be utilized in HIV treatment programs. Researchers
in the area of drug resistance will be able to
address important questions regarding HIV

genetic diversity and drug resistance patterns
through use of the proposed data base.
Population biologists will be able to develop
and test models of the spread of drug resistant
viruses as therapy is introduced into new areas.
And finally, knowledge of drug resistance patterns will direct the prioritization and need for
new antiretroviral agents.
The global program will solicit participation from both developed and resource-limited
countries. In developed countries where ART
has high penetration among persons living
with HIV, there are already excellent existing
networks to monitor HIV drug resistance. The
global program will create important linkages
between these established programs and will
permit us to achieve a truly global view of HIV
drug resistance. One of the goals of the global
program is to establish quality controlled drug
resistance testing sites in resource limited settings. The knowledge and expertise of the
leaders from established programs in developed countries will enable technology transfer
to resource limited settings.
Drug Resistant HIV- Evolution and
Containment
In developed countries, the introduction of
ART was followed shortly by the appearance of
drug resistant HIV (2). HIV, like all living
organisms has mechanisms that facilitate survival in the presence of drugs that inhibit
growth. Variants of HIV that are resistant to
drugs exist prior to drug exposure and become
the predominant population when replication
is inadequately suppressed, as is the case with
single drug therapy (3). The high levels of
HIV, the rapid turnover of HIV producing