Researchers at Johns Hopkins have concluded that
sudden, temporary spikes in the amount of HIV in the body,
commonly called "blips," generally do not mean the virus is
developing resistance to AIDS drugs and gaining strength in
"These results should provide relief to hundreds of
thousands of HIV-positive patients in the United States
currently taking drug therapy, called highly active
anti-retroviral therapy, or HAART, and reassure them that
their medications have not failed," said senior study
author and infectious
disease specialist Robert Siliciano, a professor at the
School of Medicine and a Howard Hughes Medical Institute
investigator. "Physicians and patients now have a much
better idea of when to worry about these blips and when not
Because HIV mutates rapidly, physicians and patients
have worried that even small, temporary increases in the
amount of virus could indicate the virus had mutated to
evade anti-viral drugs being taken.
Instead, the Johns Hopkins team has shown that these
so-called blips are mathematical artifacts, or variations,
that stem from the test used to gauge the amount of virus
in the body, a measurement known as viral load.
According to the findings, to be published in the
Journal of the American Medical Association online Feb. 16,
unless the blip is higher than 200 copies per milliliter of
blood, or persists upon repeated testing, it does not
signal that the virus has mutated, or changed form.
True drug resistance requires changes in therapy that
can be very difficult for the patient, Siliciano said.
Different combinations of medications can have toxic side
effects, such as lipid abnormalities and diabetes, and can
be considerably harder to tolerate than the originally
prescribed drug cocktail. Today's anti-HIV drug treatments
quickly suppress the virus to nearly undetectable levels,
but blips are a frequent problem. Earlier studies suggested
that blips occur in 11 percent to 46 percent of patients,
while the Johns Hopkins study, which used intensive
sampling, found blips in 90 percent of patients.
To see whether or when blips mean possible mutation,
the Johns Hopkins team conducted a detailed genetic
analysis of multiple blood samples from 10 HIV-positive
patients, taking samples every two to three days for a
period of three months between June 2003 and February 2004.
All patients had their infection under long-term control,
on HAART, and with viral loads of less than 50 copies per
milliliter for at least six months. In total, 36 blood
samples were taken from each patient.
Statistical analysis of the results showed that blips
occurred in nine of the 10 patients with a median viral
load of 79 copies per milliliter. The duration of the blips
was typically less than three days, and blips were not
related to any demographic factors, such as gender or age,
nor to any clinical factors, such as illness, vaccination
or differences in antiretroviral drug regimens.
For every blip, the researchers conducted genetic
tests on the samples before, during and shortly after the
blip, to uncover any mutations in the virus. Measures of
viral load were confirmed by using two independent
laboratories to test each sample.
No new mutations were found in an analysis of nearly
1,000 viral clones for mutations in HIV's two key enzymes
that are blocked by drug therapy, protease and reverse
transcriptase. The authors also found that blips were not,
again, detected when blood samples were assayed twice in
"The lack of any consistency among the tests performed
on blood samples confirms that there is no danger from
these blips in viral load," said study lead author and
infectious disease specialist Richard Nettles, an assistant
professor. "These blips can be attributed to random
statistical artifact inherent in measurements of very low
amounts of virus."
Siliciano warns that drug resistance is a growing
problem in AIDS therapy as the virus can mutate faster than
medical research can develop new drugs. When HIV becomes
resistant to one drug, it may also become resistant to
other drugs in the same class. With only four classes of
HAART drugs — for a total of 20 drugs — the
number of available combinations is limited for people who
have developed drug resistance.
Funding for this study, conducted solely at Johns
Hopkins, was provided by the National Institutes of Health,
the Doris Duke Charitable Foundation and the Howard Hughes
Medical Institute. Other researchers who took part in this
study were Tara Kieffer, Patty Kwon, Daphne Monie, Yefei
Han, Teresa Parsons, Joseph Cofrancesco Jr., Joel Gallant,
Thomas Quinn, Brooks Jackson, Charles Flexner, Kathryn
Carson, Stuart Ray and Deborah Persaud.
Currently, there are more than 40 million people in
the world living with HIV, including an estimated 950,000
in the United States and 23,000 in Maryland. Nearly half of
all HIV-infected patients in the United States develop
resistance to one or more classes of treatment