Blips and AIDS therapy

Researchers at Johns Hopkins have concluded that sudden, temporary spikes in the amount of HIV in the body, commonly called blips, do not always mean the virus is developing resistance to AIDS drugs.

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 of patients, while the Hopkins study, which used intensive sampling, found blips in nine-tenths of patients.

HIV-positive patients in the United States currently taking drug therapy, called highly active anti-retroviral therapy, or HAART,can be reassured that their medication has not failed," says senior study author and infectious disease specialist Robert Siliciano, M.D., Ph.D., a professor at The Johns Hopkins University 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 to worry."

HIV mutates very rapidly and 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.

The Hopkins team has shown that these so-called blips are variations, that stem from the test used to gauge the amount of virus in the body, a measurement known as viral load.

Their findings show that unless the blip persists upon repeated testing, it does not imply that the virus has mutated, or changed form.

Changes in therapy to cope with drug resistance can be very difficult for the patient,says Siliciano. Different combinations of medications can have toxic side effects, and can be even harder to tolerate than the originally prescribed drug cocktail.

To check for possible mutation, the Hopkins team conducted a detailed genetic analysis of multiple blood samples from 10 HIV-positive patients,they took samples every two to three days over 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.

36 blood samples were taken from each patient in total.

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.

Genetic tests were conducted for every sample, 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. In an analysis of nearly 1,000 viral clones for mutations in HIV's two key enzymes protease and reverse transcriptase; The authors also found that blips were not, again, detected when blood samples were assayed twice in independent laboratories.

The lack of any consistency among the tests performed on blood samples confirms that there is no danger from these blips in viral load," says study lead author and infectious disease specialist Richard Nettles, M.D., an assistant professor at Hopkins.

"The ability of the virus,warns Siliciano, to mutate faster than research for new drugs, means drug resistance is an immediate problem in AIDS therapy;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.