Viral Load or Virtual Virology?

Author	David Rasnick
Publisher	HEAL Toronto
Category	Viral Load
Topic	Viral Load Reliability
Article Type	Quotes & Citations
Publish Year	2000

Meta Description	The content criticizes the reliability of HIV viral load tests, citing cases of false positives/negatives and arguing that these numbers are often misleading.
Summary	This content discusses the concept of viral load in relation to HIV infection. It questions the accuracy and clinical significance of viral load measurements, suggesting that they may be misleading and not useful for diagnosing HIV infection. The content highlights studies that show discrepancies between viral load measurements and actual virus levels in the body. It also mentions instances of false-positive results in viral load tests. Overall, the content suggests that viral load measurements may not be reliable indicators of HIV infection and should be interpreted with caution.
Meta Tag	Viral Load Virtual Virology HIV Plasma PCR Test False Positives HIV-1 Viral Load Tests HIV Infection Virions Culturable Infectious Units AMPLICOR HIV-1 MONITOR Test
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By David Rasnick
August 2000
Citations from: CONTRIBUTIONS TO MBEKI'S EXPERT AIDS PANEL

From the front page, third paragraph of Roche's insert for the AMPLICOR viral load PCR test:

"The AMPLICOR HIV-1 MONITOR Test is not intended to be used as a screening test for HIV or as a diagnostic test to confirm the presence of HIV infection."

de Mendoza et al.

False positives for HIV using commercial viral load quantification assays. AIDS. 1998; 12(15): 2076-7.

"We selected 20 healthy volunteers, all of whom yield negative results for HIV antibodies using different screening tests. Plasma from all of them were analysed by three different currently available HIV viral load tests: branched DNA (bDNA) signal amplification assay (Chiron), nucleic acid sequence-based amplification (NASBA) Nuclisens (Organon Teknika), and Ultradirect reverse transcriptase (RT)-PCR Monitor (Roche)...2 samples [10%] yielded positive results by the bDNA assay...Another 2 specimens [10%] yielded false-positive results by the NASBA Nuclisens...[and] one of the 20 samples [5%] was interpreted as positive by the Ultradirect RT-PCR Monitor assay...using the Monitor test with non-B primers, up to 4 of the 20 samples [20%] yielded positive values...Results were reproduced in more than half of tested specimens for which plasma volumes were enough for repeat testing"

Schwartz D. H. et al.

"Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of false-positive PCR" (1997) The Lancet 350: 256-259.

In this case report we discover that the patient:

tested positive by PCR, but antibody negative.
had a "viral load" of 100,000 copies RNA per ml, called false positive.
was subjected to $5000 worth of PCR testing to get the "right" answer -- negative.

Christine Defer et al.

"Multicentre quality control of polymerase chain reaction [viral load] for detection of HIV DNA" (1992) AIDS 6: 659-663

"False-positive and false-negative results were observed in all laboratories (concordance with serology ranged from 40 to 100%)."

Michael P. Busch et al.

"Poor sensitivity, specificity, and reproducibility of detection of HIV-1 DNA in serum by polymerase chain reaction" (1992) Journal of Acquired Immune Deficiency 5: 872-877.

"The results indicate that current techniques for detecting cell-free HIV-1 DNA in serum lack adequate sensitivity, specificity, and reproducibility for widespread clinical applications."

"In any event, the levels of viral (and cellular) DNA in serum appear to be so low that reproducible detection, even with use of PCR, is not currently possible."

Josiah D. Rich et al.

"Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series" (1999) Annals of Internal Medicine 130: 37-39.

"The availability of sensitive assays for plasma HIV viral load and the trend toward earlier and more aggressive treatment of HIV infection has led to the inappropriate use of these assays as primary tools for the diagnosis of acute HIV infection."

"Physicians should exercise caution when using the plasma viral load assays to detect primary HIV infection"

"Plasma viral load tests for HIV-1 were neither developed nor evaluated for the diagnosis of HIV infection"

M. Piatak et al.

"High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR" (1993) Science 259: 1749-1754.

Don't be distracted by the title of the paper, the authors were clearly in a trance. The evidence they present demonstrates exactly the opposite:

"Plasma virus levels determined by QC-PCR [viral load or HIV RNA copies/ml in Table 1.] correlated with, but exceeded by an average of 60,000-fold, virus titers measured by endpoint dilution culture." By this they mean a form of pseudo isolation: "Plasma culture (TCID/ml)" -- the column with the most zeros in Table 1.

In fact, 53% of the viral load positive patients had no culturable HIV. "For HIV-1 propagated in vitro, total virions have been reported to exceed culturable infectious units by factors of 10⁴ to 10⁷, ratios similar to those we observed in plasma."

So next time you hear a viral load count get out your calculator and divide by a number between 10,000 and 10,000,000 and you might reach an approximation of reality.

Table 1. [detail] Virologic and clinical summary for 66 consecutively studied HIV-1-infected patients. [full table]

Haynes W. Sheppard et al.

"Viral burden and HIV disease" (1993) Nature 364: 291.

"...the high level of plasma virus observed by Piatak et al. [reference above] was about 99.9 per cent non-culturable, suggesting that it was either neutralized or defective."

Of course, "neutralized" or "defective" virus is of no clinical significance for the patient. "Viral load" numbers are nothing but a laboratory artifact concocted by over zealous HIV researchers to try to save their bankrupt HIV=AIDS hypothesis.