|HIV||Etiology||Viral load||Correlation with co-culture|
|High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.|| ||Piatak M Jr et al.
| ||“Circulating levels of plasma virus determined by QC-PCR also correlated with, but exceeded by an average of nearly 60,000-fold..., titers [amounts] of infectious HIV-1 determined by quantitative endpoint dilution culture of identical portions of plasma...Total virions have been reported (in other studies) to exceed culturable infectious units by factors of 10,000 to 10,000,000, ratios similar to those we observed in plasma” This study showed that viral load test results do not correlate with... the finding of virus by co-culture (53% of HIV positives with detectable levels of viral loads had 0 (zero) virus by co-culture including people with viral loads as high as 815,000 copies per milliliter) => the number of viral copies estimated by these tests represent between 99.99% and 99.9999% non-infectious viruses which are not considered to be able to cause disease, since by definition they cannot infect cells.|
| ||Science. 1993 Mar 19;259:1749-54.||1993|
|Manufacturer's notice|| ||Roche
| ||"Quantitative [co-]culture has limited utility for monitoring virus levels in infected individuals since only a small fraction of virus particles is infectious in vitro. Infectious virus is often undetectable in asymptomatic individuals...|
| ||Amplicor HIV-1 Monitor Test||1996|
|Viral burden and HIV disease.|| ||Sheppard HW, Ascher MS, Krowka JF.
| ||“the high level of plasma virus observed by Piatak et al, was about 99.9 per cent non-culturable, suggesting that it was either neutralized or defective. Therefore, rather than supporting a cytopathic model, this observation actually may help explain the relatively slow dissemination of the infected cell burden and thus the relative ineffectiveness of therapy with nucleoside analogues which target this process.”|
| ||Nature. 1993 Jul 22;364(6435):291-2.||1993|
|Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction.|| ||Bagasra O et al.
| ||“Our study of PBMC [Peripheral Blood Mononuclear Cells] from 56 HIV-1-seropositive patients, using in situ hybridization alone, also [as did other studies] revealed only 1 in 5000 to 1 in 100,000 cells positive for HIV-1-specific nucleic acids [DNA]...Our finding with the use of in situ PCR that large numbers [if you consider 0.1% to 13.5% of cells a ‘large number’] of PBMC from HIV-1-seropositive patients contain the provirus suggests that direct cytopathic [cell-killing] effects of the virus may be an important but not necessarily the sole cause of depletion of CD4-positive lymphocytes. "|
| ||NEJM. 1992;326(21):1385-91.||1992|