Viral Load: How Low Can You Go?

For nearly three years, viral load (plasma RNA) measurement has been the gold standard of HIV disease prognostic markers.

Initially, viral load was used as a predictor of disease progression. With the advent of protease inhibitor use, the test has been employed to evaluate the efficacy of combination therapies and the emergence of drug resistance. Low plasma RNA levels are highly associated with prolonged survival in HIV-infected individuals and, excluding viral eradication, have been the ultimate goal of antiretroviral therapy. What is low? Under 4,000? 400? 40?

In terms of progression to AIDS or death, lower viral load has always been better, but many numbers have been bandied about as "pretty good." A viral load under 3,000 copies is associated with low risk of progression to AIDS. Eleven thousand copies doesn't sound so bad if you've come down from 900,000. Twelve hundred copies down from 60,000? After enduring years of what we now know is sub-optimal therapy, many people have to live with a viral load far above the level of detection at the risk of developing drug resistant virus because it's the best they could get.

One of the more recent applications of viral load testing stems from its potential as a predictor of the durability of a given drug regimen -- in other words, how long the combination will work for an individual. In a retrospective study of patients taking ritonavir-containing regimens, Dr. Dale Kempf of Abbott Laboratories and colleagues observed "a strong correlation between the durability of response and the nadir (lowest point) in the RNA curve for each patient." They found lesser correlations to baseline viral load and the initial drop in viral load. However, neither the duration of response to treatment nor the decline in viral load correlated with initial CD4 counts. (A report on this study can be read in its entirety in the medical journal AIDS, Vol. 12, No. 5, which is available in the HIV Resource Center at AIDS Project Los Angeles.)

Simply put, the lower a person's viral load becomes on drug therapy, the longer that therapy may work for them. For HIV-infected individuals who are less treatment-experienced and have more treatment options, these data fortify the rationale for a "hit hard" strategy, using a fully suppressive regimen.

The plot thickens with the availability of ultrasensitive assays, which can measure viral load down to 20-50 copies. How much longer can one remain "successful" on a given regimen if their viral load goes down to 38 copies as opposed to 380 copies? At what point does an individual flirt with viral breakthrough? Although common sense would lead most to say that "less is more," at this time there is no clear answer.

What does seem clear is that languishing on dual or protease inhibitor-sparing therapy, if not maximally suppressive, may be a set up for the outgrowth of drug resistant HIV. Additionally, an ultrasensitive viral load assay must become the industry standard.

In a section examining lab results in the May POZ magazine, executive editor Sean Strub's viral load is the subject of the month. It is 28 copies. Low enough? Dr. Paul Bellman, a New York clinician with extensive experience treating HIV, states, "I would feel a lot more secure if Sean's viral load went below 20."

This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).