VANCOUVER, B.C. _ HIV-positive patients who have high levelsof HIV RNA have a three to 10 times greater chance of dying within10 years than those with low levels of virus in their body, accordingto new data presented at the XI International Conference On AIDS.
After studying more than 1,600 patients enrolled in the Multi-CenterAIDS Cohort Study (MACS), researchers at the University ofPittsburgh have further defined the extent to which the level of HIVRNA can predict the risk of HIV disease progression.
"To assess progression we can't rely on CD4 counts alone," saidJohn Mellors, associate professor of medicine and director of the PittTreatment Education Unit at the University of Pittsburgh. "Theserecent findings provide strong evidence that viral load determinationsshould be incorporated into clinical decisions about antiretroviraltherapy and patient management."
A natural history study of MACS patients shows that HIV RNAmeasurement is an earlier and stronger predictor of long-term patientoutcome than CD4 counts. The study results break out the survivaltimes of patients based on four levels of HIV RNA. Those patientswith a baseline viral load greater than 36,000 copies/ml survived amedian five years, compared to the more than 70 percent of patientswith baseline viral loads less than 4,500 copies/ml who were stillalive after 10 years.
The highest rates of progression are seen in patients who have morethan 30,000 copies/ml. For example, Mellors' study found that allpatients above that level died after nine years while only 3.4 percentof patients with less than 500 copies/ml had died at the same period.Mellors calculated that patients who experienced a one-log reductionin viral load had an 80 percent decrease in their rate of HIVprogression.
"This provides more prognostic information than CD4 and thus iscritical for understanding when we should initiate antiretroviraltherapy and when to hold off antiretroviral therapy," Mellors said."But there is a paradox here of prognosis. Individuals with the bestprognosis _ the lowest RNA, the highest CD4 _ may be those whobenefit the most from antiretroviral therapy with intent to eradicatethe virus. Intensive antiretroviral therapy in patients with low risk ofprogressing may permanently tip the balance between virus andhost."
Further evidence of the predictive value of HIV RNA comes fromnew data from a virology substudy of ACTG 175, which studied thecombination of AZT and ddI or AZT and ddC. The substudy,following more than 2,000 patients, showed that a one-log decreaseof plasma HIV RNA at baseline was associated with an 88 percentdecrease in the risk of disease progression compared to a 65 percentdecrease in risk for patients who had a one-log decrease at eightweeks. The viral load measurements were more predictive of riskthan CD4 count changes during the same period, said Scott Hammer,professor of medicine at Harvard Medical School, in Boston.
"A number of studies have now consistently shown that the plasmaHIV RNA is a stronger marker than CD4 cell count," he toldconference delegates. "But it is important to use these two markerstogether as complementary information is provided."
In addition to its prognostic value, HIV RNA quantification hasseveral diagnostic and therapeutic applications, Hammer said. HIVRNA measurements will be useful in diagnosing neonates, who havesome of the highest viral loads ever measured. Viral load also may beuseful in documenting the window period following HIV exposureand in diagnosing an acute symptomatic retroviral syndrome prior toseroconversion, he added.
AIDS Alert is published by American Health Consultants, publisherof BioWorld Today. n
-- Skip Connett AIDS Alert Editor
(c) 1997 American Health Consultants. All rights reserved.