Dissident AIDS Database

Viral loadFalse viral loadInconsistency with antibody testsGeneral
Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series.
 Rich JD, Merriman NA, Mylonakis E, Greenough TC, Flanigan TP, Mady BJ, Carpenter CC
  "Plasma viral load tests for HIV-1 were neither developed nor evaluated for the diagnosis of HIV-1 infection; therefore their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. 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)...These three cases illustrate the potential problems of using HIV-1 plasma viral load tests for diagnosis of HIV infection...Only patients who have a high pre-test probability of a positive result should be evaluated for primary infection by using plasma viral load testing...Their performance in patients who are not infected with HIV is unknown. Physicians should exercise caution when using plasma viral assays to detect primary HIV infection, particularly when the pretest probability of infection is low". This series is significant because it demonstrates that false positives on viral load may be likely to occur in conjunction with false positives on both the ELISA and Western Blot HIV antibody tests. Since the RNA assays look for RNA that is based in the amino-acid sequence of the same proteins used in the ELISA and Western Blot, this would not be surprising.
  Ann Intern Med 1999 Jan 5;130(1):37-91999
False-negative HIV viral load in AIDS patients.
 Simons P, Muyldermans G, Lacor P, Zissis G, Lauwers S
  No abstract / Pubmed
  AIDS 1997 Nov 15;11(14):1783-41997
False positives for HIV using commercial viral load quantification assays.
 De Mendoza C, Holguin A, Soriano V
  No abstract / Pubmed
  AIDS 1998 Oct 22;12(15):2076-71998
Dynamics of co-infection with M. Tuberculosis and HIV-1.
 Kirschner D
  "If this (viral) load is increased due to the presence of opportunistic infections, the disease progression is much more rapid"
  Theor Popul Biol 1999 Feb;55(1):94-1091999
1
 Cehim, C.,I., et al.,
  "HIV-I infection in only 4 (12.5%) of 32 high-risk cases" with repeatedly positive ELISAs. HIV infection was negative by Western blot, provirus amplification with the polymerase chain reaction (PCR), and virus isolation tests.
  J Infect. Dis. 164, 656-664, 19911991
Plasma viraemia in seronegative HIV-1-infected individuals
 Ensoli F, Fiorelli V, Mezzaroma I, D'Offizi G, Rainaldi L, Luzi G, Fiorilli M, Aiuti F.
  "We have performed a prospective study of 65 high-risk HIV-1-antibody-negative individuals who were followed-up for a period of at least 1 year. Twelve of these individuals were shown by polymerase chain reaction (PCR) to be carriers of HIV-1 proviral sequences. The virus was isolated from lymphocytes in five out of 10 PCR-positive subjects and from cell-free plasma in two."
  AIDS 1991 Oct;5(10):1195-91991
Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results.
 Sullivan PS, Schable C.
  “This report describes the field and laboratory investigation of eight patients who had clinical evidence of HIV infection, but repeatedly negative HIV-1 antibody screening results in the course of their clinical care. In all patients, HIV infection was proven [sic] by other diagnostic methods [PCR/viral load, p24 antigen and co-culture techniques]...”
  AIDS. 1999 Jan 14;13(1):89-961999
HIV testing: State of the Art
 Sloand, E.M., et al.,
  Even using concordance with antibody tests as a gold standard, PCR was not found to be very specific for HIV. Citing a proficiency study involving five laboratories with extensive PCR experience, Sloand states that the average speci-ficity was 94.7%." Specificity was as low as 90%. Numbers in the 90s may sound good, but in reality, this is not the case. The number of false-positives compared to true positives is dependent on the prevalence of HIV infection in any population being tested - the lower the prevalence, the more false-positives. Sloand comments that if the specificity levels achieved in this study were applied to the potential blood donor population" (blood donors now consisting of members of the low-prevalence general population), then "...for every true silent infection detected, 1800 uninfected donors would be classified as PCR positive and 3500 as PCR indeterminate. Thus PCR is clearly not suitable for routine screening of transfused blood" and by infer-ence, any low-prevalence population.
  JAMA 266, 2861-2866, 19911991
Polymerase Chain Reaction for the Diagnosis of HIV Infection in Adults : A Meta-Analysis with Recommendations for Clinical Practice and Study Design
 Owens Douglas K. et al
  “Evaluation of the performance of PCR poses difficult methodologic challenges... Typically, a new test is compared with a superior reference (or gold standard) test…The lack of an appropriate reference test [for PCR] substantially complicates evaluation…[using the Western blot as a gold standard] We sought to 1) assess the validity and reliability of the scientific evidence on the diagnostic accuracy of PCR; 2) characterize the sensitivity and specificity of PCR on the basis of a formal analysis of the available studies… We assessed the appropriateness of the study design for the evaluation of the diagnostic performance of PCR on a four-point scale (1,2,3, or 4). A rating of 1 indicated that the design made the study susceptible to significant bias; a rating of 4 indicated that the study design satisfied all criteria for the evaluation of diagnostic tests... Reported sensitivities for PCR range from 10% to 100%, and specificities range from 40% to 100%. A summary receiver-operating characteristic curve based on all 96 studies has a maximum joint sensitivity and specificity of 97.0% to 98.1%... The PCR assay is not sufficiently accurate to be used for the diagnosis of HIV infection without confirmation. Use of PCR for the diagnosis of HIV in adults should be limited to situations in which antibody tests are known to be insufficient.” [Perth Group analysis : In this analysis the numbers of studies receiving a rating of 1, 2, 3, or 4 for overall study design were 73, 12, 6, and 5, respectively… All studies that were awarded a rating of 4 or 3 (11) used both negative and positive controls and were also blinded.However, of the 11, 6 did not satisfy other criteria (for example the "diseased" and "control" population may have received different reference tests). Secondly, it is not sufficient merely to have controls, controls should not be a "non-diseased" population and even less blood "donors" as is the case in the Owens et al analysis. The control patients should consist of sick individuals diagnosed with diseases and laboratory abnormalities resembling as closely as possible the abnormalities characteristic of AIDS patients].
  Annals of internal medicine, 1 May 1996 | Volume 124 Issue 9 | Pages 803-8151996
VIRAL LOAD e PCR
 Johnson Christine
  "In a FAX I received from the Centers for Disease Control (CDC) in 1994 regarding PCR, they stated that "Neither its speci-ficity nor its sensitivity is known," and that "PCR is not recommended and is not licensed for routine diagnostic purposes. In a nutshell, "The specificity of any form of PCR, for the HIV genome, has not been determined."
  CONTINUUM vol 4,nr 41
Manufacturer's notice
 Roche Molecular Systems.
  The manufacturers' statement in test package inserts note that "the 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" .
  Amplicor HIV-1 Monitor test, version 1.5. 58003466-01. August 2002.2002
False positives for HIV using commercial viral load quantification assays.
 Mendoza C, Holguin A, & Soriano V
  The plasma of 20 healthy volunteers, all of whom yielded negative results for HIV antibodies using different screening tests, were analyzed by three currently available HIV viral load tests. The first assay, which used a branched DNA assay from Chiron laboratory, found that 2 of the 20 volunteers (10%) had a positive viral load. The nucelic acid based amplification test, from Organon Teknika, also yielded 2 of 20 false positives. For the final assay, RT-PCR Monitor from Roche, a false positive rate of 20% was found. The authors do not reveal whether the same people who tested positive on one assay were more likely to test positive on another, but they do state that repeat testing reproduced the same results in more than half of the specimens that were able to be retested
  AIDS, 1998, 12(15); 2076-20771998
Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of a false positive PCR
 Schwartz DH et al.
  The patient was a participant in an HIV vaccine clinical trial who was being carefully followed and whose blood had been tested for antibodies to HIV every few months for several years. A viral load test was first performed on his serum (positive) when the patient reported flu-like symptoms. The authors then decided to run viral load tests on all of the available samples of blood from that patient which had been stored over the course of the clinical trial which turned out to be positive (with the largest viral load being "in the range of 10,000 to 100,000") while the antibody tests on these serum samples had all been negative. This patient had repeated antibody testing for the next year which continued to show negative results.
  Lancet, 1997, 350; 256-259.1997
Acute HIV Infection among Patients Tested for Mononucleosis.
 Rosenberg ES, Caliendo AM, Walker BD
  A study found very high viral loads in people who were negative on the HIV antibody tests, with the highest being greater than 1.5 million copies per mL. This study was designed as an attempt to see if people diagnosed previously with acute mononucleosis were actually having symptoms of acute HIV-infection.
  New England Journal of Medicine, 1999, 340 (12):969.1999
Diagnosis of primary HIV-1 infection.
 Daar ES, Little S, Pitt J, Santangelo J, Ho P, Harawa N, Kerndt P, Glorgi JV, Bai J, Gaut P, Richman DD, Mandel S, Nichols S
  "Follow-up was not available for these 127 patients (cohort 1); therefore, before testing any samples, we determined that an HIV RNA result above 10,000 copies/mL would be considered a true-positive result. ... Two of 127 patients in cohort 1 were negative for HIV antibody and negative for p24 antigen, but positive for HIV RNA with levels of greater than 100,000 copies/mL. For the purpose of this analysis, they were considered to be true positive for primary HIV infection." (which is totally abitrary). This study also looked at two other cohorts of people at risk for HIV infection in which antibody testing was available, and they found that 8 of 217 (3.7%) subjects had a false positive result, with viral loads ranging from 50 to 2000 copies/mL. Because the authors include cohort 1 in their data even though no follow-up data is available for this cohort, their conclusions and abstract report a lower false positive rate of 2.6%.
  Ann Intern Med, January 2, 2001;134(1):25-92001
Incidence and prevalence of HIV, hepatitis B virus, and cytomegalovirus among health care personnell at risk for blood exposure: Final report from a longitudinal study.
 Gerberding JL
  In this study, they did PCR tests on 133 of the 327 healthy workers who had experienced needle sticks in their clinic. All of these 133 subjects remained HIV negative on the ELISA antibody test, but seven of them had "indeterminate" PCR results, and four others had one or more actual positive results, for a false positive rate of 3%. If the indeterminate results are counted as well, the false positive rate is 8%. "The failure to demonstrate seroconversion... among those with positive PCR tests suggests that false positives occur even under stringent test conditions. The low predicitive value of a positive or indeterminate PCR test... contraindicates the routine use of gene amplification in this clinical setting."
  J Infect Dis, 1994, 170; 1410-14171994
Molecular diagnostics. The polymerase chain reaction and its use in the diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae.
 Uhrin M.
  The diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae was performed using classical microbiological techniques of chlamydial cell culture and agar isolation respectively in patients studied in Pittsburgh. The polymerase chain reaction (PCR) was compared to standard procedures used for diagnosing these sexually transmitted organisms. Statistically significant differences were observed in molecular diagnostics versus classical isolation techniques. Numerous specimen handling problems were identified in the handling of Neisseria. The enhanced ability to diagnose these sexually transmitted organisms is discussed in relation to HIV
  Gac Med Mex 1997;133 Suppl 1:133-71997
Scientists Race to Detect SARS, but First They Must Test the Test
 POLLACK ANDREW and ALTMAN LAWRENCE K
  "The C.D.C. says polymerase chain reaction tests also tend to produce false positives, so that any positive finding should be confirmed by repeating the test or having the specimen tested by another laboratory."
  The New York Times June 3, 20032003