Early Testing Can Identify HIV Treatment Failure
After reviewing data obtained from three clinical trials involving a total of 124 patients, researchers found that a persons response to antiretroviral therapy on day six was a strong predictor of whether the therapy would fail several weeks later.
"If a person doesnt have an early response to drug therapy, evidenced by an early drop [in viral RNA], theyre not likely to have a good long-term response," said Michael Polis, M.D., senior investigator at the National Institute of Allergy and Infectious Diseases. Polis is the lead author of the report, which appeared in the Nov. 24, 2001, Lancet.
|Garlic May Affect Saquinavir Metabolism |
14 December 2001 A preliminary study in healthy volunteers suggests that long-term use of garlic supplements may decrease patients' plasma level of the antiretroviral drug saquinavir.
On average, the concentration of saquinavir present in the nine volunteers plasma fell to half of the baseline amount after they began taking a garlic supplement, according to a report in the Jan. 15, 2002, issue of Clinical Infectious Diseases.
The apparent effect of garlic on saquinavir metabolism persisted after the volunteers stopped taking the supplement. After a "washout" period during which patients received neither garlic nor saquinavir for 10 days and then took saquinavir for three days, plasma levels of the drug were about 3040 percent lower than at baseline.
The research team speculated that garlic alters the cytochrome P-450 pathway through which saquinavir is metabolized and decreases the bioavailability of the drug.
The daily "garlic dose" used in the study was about the same as that contained in eight grams of garlic cloves.
Polis and colleagues found that most patients whose plasma HIV RNA concentration had fallen by about 50-fold or more between baseline and day six of therapy were also likely to have had a low viral RNA level at week 12. About 84 percent of the time, the researchers could use data obtained during the first six days of therapy to determine which patients would have a low plasma viral RNA level after 12 weeks of therapy.
But Polis described as "much stronger" his groups ability to predict which patients' treatment would fail.
Ninety-nine percent of the time, patients whose plasma viral RNA level had not decreased by about fivefold on day six also had a high viral RNA level by week 12 of therapy.
The day-six evaluation suggests that ineffective drug regimens can be stopped early during treatment, potentially limiting adverse drug events in patients and lessening the emergence of antiretroviral resistance.
"This is a good way of sparing the persons exposure to the toxicities of some agents, and also for saving some drugs that may be efficacious," Polis said.
Current U.S. guidelines recommend the use of a drug regimen for at least four weeks before determining its success against HIV.
"In general," Polis noted, "persons are not evaluated for the first two to four weeks of therapy."
According to the report, the day-six viral RNA level had dropped precipitously in all of the patients who were receiving highly active antiretroviral therapy (HAART) consisting of zidovudine, lamivudine, nevirapine, and indinavir. Patients whose viral RNA level remained high on day six had received a single-drug regimenthe protease inhibitor indinavir or ritonavir. These patients were treated before HAART became the standard of care for HIV-infected patients.
None of the patients whose data was used for the analysis had taken a study drug before beginning antiretroviral therapy. In the report, Polis and colleagues advised that their findings be examined in prospective studies involving larger numbers of patients, including people who have already used an antiretroviral drug.