WASHINGTON _ AIDS researchers may have a new tool forpatient management and clinical trial data collection. In a studypublished in the November 1994 Journal of Infectious Diseases,Chiron Corp.'s branched (bDNA) assay measured viral load in HIV-infected patients more sensitively and reproducibly than standardtests, including blood culture techniques and the p24 antigen captureassay.Monitoring viral burden more accurately could allow researchers tobetter understand disease progression in AIDS and could helpdetermine when to start, stop or switch therapies for individual AIDSpatients."The ability to measure levels of HIV in the blood is critical becausechanges in the amount of circulating virus may predict a patient'sclinical course," said Clifford Lane, clinical director of the NationalInstitute of Allergy and Infectious Diseases, in a prepared statement."The branched DNA assay is a sensitive, reproducible and rapidmethod for evaluating HIV viral burden at all stages of infection."The study, which was supported by an NIAID grant, showed that in102 patients enrolled in clinical trials of antiretroviral and immune-based experimental AIDS drugs, the bDNA assay detected virus-associated RNA in 74 percent of patients while the p24 assay foundviral proteins in 60 percent of patients. In a subset of 56 patients, thebDNA assay detected virus in 89 percent of patients while bloodculture tests detected virus in 61 percent of patients.However, the journal article did not state whether the differencesbetween the assays were statistically significant, an important clue asto the strength and validity of the findings. NIAID researchers couldnot be reached at press time.The bDNA assay also was able to measure viral burden in patientswho had high counts of critical immune system CD4 cells and whoare thus considered at an early stage of disease. "These resultssuggest that the assay could be used to monitor patients at all stagesof disease," said Lane.Blood culture techniques are labor-intensive and results can varyfrom hospital to hospital and laboratory to laboratory, according toNIAID. The p24 antigen assay measures HIV-produced proteins inthe blood but may not capture the full amount of viable HIV in apatient's blood. The bDNA assay measures the amount of RNA, thegenetic material of HIV, in virus particles in a patient's blood.The study also demonstrated that bDNA-measured increases in viralload corresponded with decreasing amounts of critical immunesystem CD4 cells. The correlation was statistically significant (pvalue less than 0.05). Currently, researchers rely heavily upon"surrogate markers," such as CD4 cell counts, to measure diseaseprogression. During HIV infection, CD4 counts are depleted.However, changes in CD4 counts have thus far not been associatedwith improved clinical outcome in AIDS patients.Spencer Cox of the Treatment Action Group (TAG) in New Yorksaid it remains to be seen how direct the correlation between viralburden and clinical outcome is. He said that no one has shown astatistically significant link between decreasing levels of virus in theblood and improving health in AIDS patients. Another unansweredquestion in AIDS research is whether it's the magnitude of change insurrogate markers or viral load (i.e. a sharp decrease in viral load ora sharp increase in immune-boosting CD4 cells) or the duration ofthat change (i.e. dramatically higher or lower levels for two weeksversus moderately higher or lower levels for two months) that makesa difference for patients.He said he was not that impressed by a viral load assay that wasbetter than the p24 assay. "The p24 assay was an easy standard tobeat since it was useless as a marker of treatment effect," Cox toldBioWorld. "p24 was not a good surrogate marker and most peoplebelieve that the new measures of viral burden will be better." n
-- Lisa Piercey Washington Editor
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