Scientists from Johns Hopkins and Uganda say that counting
the number of HIV viruses in the
blood rather than relying solely on counting the number of
circulating HIV-fighting CD4 immune
system cells is a far better way to uncover early signs
that antiretroviral drugs are losing their punch,
and to signal the need to get patients on more potent
treatments to keep the disease in check.
In a new study, presented at the 2009 Conference on
Retroviruses and Opportunistic
Infections held Feb. 8 to 11 in Montreal, the expert team
compared treatment-failure predictability
of the HIV so-called viral load test to the one that counts
immune system CD4 cells to track the
disease's progression in 1,133 HIV-positive Ugandan men and
women.
Viral load testing, the experts say, has long been
considered the gold standard but has not been
as widely used as CD4 testing in developing countries
because, at $20 to $50 per test, it costs at
least four times more than the CD4 test.
But study results show that it is worth adopting more
widely because it is more accurate in
predicting treatment failure, according to lead study
investigator and infectious diseases specialist
Steven Reynolds, an assistant professor at the
Johns Hopkins University School of Medicine and a
staff clinician at the U.S. National Institute for Allergy
and Infectious Diseases.
Overall, viral load testing confirmed that 80 people
(7.1 percent) were failing on drug
treatments. A majority (62) of the treatment failures,
however, were not detected by standard CD4
test counts. All participants were tested every six months
for the three-year duration of the study.
However, CD4 testing by itself identified 125
treatment failures, most of which (107) were
subsequently proven not to be failing by virologic
monitoring. Only 18 infected people were correctly
identified as patients with treatment failure by both
tests. In general, drug treatment is considered a
failure if it does not suppress viral particles in the
blood to nearly undetectable levels.
Reynolds says the new results may lead to changes in
HIV-monitoring and -testing guidelines
from the United Nations' World Health Organization.
"Our results clearly show that practicing current CD4
immunologic monitoring guidelines, as
recommended by WHO, wrongly identifies drug failures in
infected people and misses a large number
of infected people who are failing and need to switch to
more potent medications," says Reynolds, who
is also a medical microbiologist.
Since 2004, Reynolds and his team of experts have been
studying various means of preventing
and treating the disease among 12,000 people in Rakai,
Uganda.
Early study findings, he says, prompted the Rakai team
to switch annual and biannual monitoring
practices to viral load tests only, despite the increased
costs.
"Detecting antiretroviral drug failures accurately and
early is essential to avoiding HIV drug
resistance, which could result in HIV disease progressing
to AIDS and leading to illness and death,"
Reynolds says.
Reynolds points out that although patients can be
switched to more potent drugs after a
treatment failure, their HIV virus becomes resistant to the
older regimen and they cannot go back.
"So switching limits their treatment options, and it
also costs a lot more," he said. "And in
developing countries with limited resources, maximizing the
number of people and their duration on
first-line therapy through adherence and monitoring is
critical."
First-line drug regimens, he notes, usually consist of
a cocktail of three drugs, usually
zidovudine (AZT), lamivudine (3TC) and nevirapine
(Viramune), which cost nearly $240 per year. The
second-line, more powerful drug regimens, often made up of
tenofovir (Viread), emtricitabine
(Emtriva) and lopinavir (Kaletra, Alluvia) cost as much as
$750 per year.
More than 90 percent of the 2 million people infected
with HIV in sub-Saharan Africa are
currently taking first-line antiretroviral therapy.
In the study, conducted jointly by Johns Hopkins and
Rakai Health Sciences Program
researchers, the experts defined a drug failure as evident
when a viral count per cubic millimeter of
blood jumped to more than 10,000 copies, or when viral
counts rose sharply, with back-to-back tests
showing a rise of at least 400 copies per cubic millimeter
of blood.
Blood testing for a strong immune response to the
viral infection is measured by the number of
CD4 cells and reported as a treatment failure if there is
either a persistent CD4 count that is less
than 100 per cubic millimeters of blood or if there is a
steep drop of at least 50 percent in immune
cells, or if CD4 levels fall below those detected when drug
therapy was started.
Researchers involved in the study are Reynolds,
Gertrude Nakigozi, Kevin Newell, Anthony
Ndyanabo, Ronald Galiwongo, Iga Boaz, Thomas Quinn, Ronald
Gray, Maria Wawer and David Serwadda.
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