The prevalence of HIV resistance to protease inhibitors fell
sharply between 2003 and 2010, according to a study presented to the 51st
ICAAC meeting in Chicago.
Investigators from Monogram Biosciences analysed the profile
of almost 70,000 stored blood samples with resistance to at least one
antiretroviral drug. Over the seven years of the study, the percentage of
samples with resistance to a protease inhibitor fell by half.
A marked fall was also observed in the proportion of samples
with resistance to drugs in the three main antiretroviral classes.
HIV can develop resistance to the drugs used in
Early generations of anti-HIV drugs had a low genetic
barrier to resistance, and demanded extremely high levels of patient adherence.
This was especially the case with unboosted protease inhibitors, some of which
needed to be taken two or three times daily and also had complicated food and drink
However, since 2000 there have been significant improvements
in HIV care, including the almost universal adoption of ritonavir-boosting of protease
inhibitors. These drugs have a powerful anti-HIV effect. Even if they fail to
suppress viral load, this rarely involves the emergence of drug-resistant
Improved drugs in the nucleoside reverse transcriptase inhibitor
(NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) classes have been
introduced, and completely new classes of antiretrovirals such as entry and
integrase inhibitors have been developed. This means that an undetectable viral
load is now the aim of HIV therapy, regardless of a patient’s treatment history
or resistance profile.
Resistance tests are an integral component of HIV care and
are used to guide the choice of suitable antiretroviral agents. Investigators
from Monogram Biosciences wished to see if the prevalence of virus resistant to
any protease inhibitor, NRTI, or NNRTI had changed in recent years. They also
wished to establish trends in the prevalence of single, dual and triple class
A total of 68,587 samples submitted to their laboratories
between 2003 and 2010 for resistance testing were analysed.
In 2003, a total of 52% of samples had detectable resistance to a
protease inhibitor. However, this had fallen to 26% by 2010 (p < 0.05).
“A strong trend of decreasing prevalence of protease inhibitor
resistance was observed in the…database between 2003 and 2010,” comment the
Prevalence of NRTI resistance also fell from 77% to 70% (p
< 0.05), and there was also a fall in the proportion of samples with
evidence of resistance to NNRTIs (70% to 61%; p < 0.05).
Moreover, there was also a significant decline in the
proportion of blood samples with triple-class resistance. Prevalence fell from
29% in 2003 to 11% in 2010 (p < 0.05). The prevalence of dual-class
resistance also fell, from 40% to 35%. These falls were accompanied by an
increase in the proportion of samples with resistance to one class of drug
(31% to 54%; p < 0.05).
The resistance profile of samples with dual-class resistance
was examined in more detail.
In 2003, resistance to NRTIs and NNRTIs was detected in 54%
of samples; 37% exhibited resistance to protease inhibitors and NRTIs; and 9%
showed evidence of resistance to protease inhibitors and NNRTIs.
By 2010, however, dual-class resistance profiles had changed
significantly. Resistance to NRTIs and NNRTIs was evident in 70% of samples;
protease inhibitor and NRTI resistance in 24%; and protease inhibitor and NNRTI
resistance in 7%.
The investigators believe their results “may have important
implications for ARV [antiretroviral] selection, clinical trial design and drug