Item #45: Does ‘Viral Load’ Measure Live Virus?

Generally speaking, HIV can be isolated only by “reactivating” latent copies of the virus, and then only with extraordinary difficulty. Viral load, one of the clinical markers for HIV, is not a measurement of actual, live virus in the body but the amplified fragments of DNA left over from an infection that has been suppressed by antibodies.

Farber writes "Viral load, one of the clinical markers for HIV, is not a measurement of actual, live virus in the body, but the amplified fragments of DNA left over from an infection that has been suppressed by antibodies".

This is nonsense. First, viral load assays do not measure DNA, they measure HIV's content of RNA genomes (HIV is an RNA-containing, not a DNA-containing virus). Second, there is ample evidence that the signals from plasma viral load assays are proportional to the infectious virus content of plasma. In numerous studies monitoring cohorts of HIV patients, viral load increases with time. 71 How is this possible if all that is left over are the “fragments ... from an infection that has been suppressed”?

It is strange that the Gallo document would claim that “In numerous studies monitoring cohorts of HIV patients, viral load increases with time”. How is this possible if all that is left over are the ‘fragments ... from an infection that has been suppressed’? given that viral load is usually monitored in AIDS drug experiments which, if effective, should lower viral load. Their only reference for this point actually shows something considerably different. The reference is to a NIAID/NIH website [1] which is anonymous and not peer reviewed. The graph on this website is taken from a 1993 review paper by Pantaleo [2]. Not being a research paper, this graph did not originate there, but in another non-research paper, a 1991 summary of an NIH conference moderated by Anthony Fauci [3]. It is fairly clear that this graph was not drawn from actual data, but is just illustrative. This is because no source is given for the data, the paper is a summary of a conference not a report of original research and the title is “Typical course of HIV infection”.

Pantaleo described what is seen in this graph, in another 1993 paper [4] “Primary infection with [HIV] is generally followed by a burst of viraemia [high ‘viral load’] with or without clinical symptoms. This in turn is followed by a prolonged period of clinical latency. During this period there is little, if any, detectable viraemia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells”.

Viral load tests definitely have problems when used on an individual basis (as opposed to observing changes in average values). These problems include:

• False Positives…“We report the case of a sexually active woman with symptoms suggestive of ARS [Acute Retroviral Syndrome] who had a false-positive HIV-1 RNA assay result...Laboratory evaluation revealed negative results on HIV-1 ELISA and Western blot [antibody tests]. However, an HIV-1 RT-PCR [viral load] assay...revealed a viral load of 623 copies/ml, through p24, gp120, and gp160 antigens were not present” [5] and…

  “We report two cases of false-positive results obtained by using branched-chain DNA assay...and one case...by using HIV reverse transcriptase polymerase chain reaction (RT-PCR)” [6].

• Lack of Utility…“The 2 articles recently published in JAMA are probably among the most important HIV-related papers of the year and have tremendous implications for decision-making. They question the rather arbitrary viral load threshold used in current antiretroviral guidelines and suggest that the main factor that should influence when to start therapy – and maybe the only one to consider – should be the CD4+ cell count.” [7].
• Association with Parasitic Worms (indicating that ‘viral load’ is not specific to HIV, as the level could be reduced by reducing the number of parasitic worms)…“56 clinically asymptomatic HIV-1-infected individuals [from Ethiopia], 31 (55%) of whom were also infected with helminths [intestinal worms], were studied…At baseline, HIV plasma VL [viral load] was strongly correlated to the number of eggs excreted and was higher in individuals infected with more than one helminth. After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group” [8].

It is sometimes said that plasma viral load is less relevant than the load of virus in the tissues. We close with a comment from a 1999 paper “The results obtained for patients with a broad range of plasma viral loads before and after antiretroviral therapy reveal a constant mean viral (v)RNA copy number (3.6 log10 copies) per infected cell, regardless of plasma virus load or treatment status.” [9].

1. niaid.nih.gov/publications/hivaids/9.htm.
2. Pantaleo G et al. The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med. 1993 Feb 4; 328(5): 327-35.
3. Fauci AS et al. NIH conference. Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1991 Apr 15; 114(8): 678-93.
4. Pantaleo G et al. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25; 362: 355-8.
5. More D et al. Utility of an HIV-1 RNA assay in the diagnosis of acute retroviral syndrome. S Med J. 2000 Oct; 93(10): 1004-6.
6. Rich JD et al. Misdiagnosis of HIV Infection by HIV-1 Plasma Viral Load Testing: A Case Series. Ann Intern Med. 1999 Jan 5; 130(1): 37-9.
7. Tebas P. When should antiretroviral therapy be initiated? Medscape HIV/AIDS. 2002; 8(1).
8. Wolday D et al. Treatment of Intestinal Worms Is Associated With Decreased HIV Plasma Viral Load. J Acquir Immune Defic Syndr. 2002 Sep 1; 31: 56-62.
9. Hockett RD et al. Constant Mean Viral Copy Number per Infected Cell in Tissues Regardless of High, Low, or Undetectable Plasma HIV RNA. J Exp Med. 1999 May 17; 189(10): 1545-54.