TY - JOUR
T1 - Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of false-positive PCR
AU - Schwartz, David H.
AU - Laeyendecker, Oliver B.
AU - Arango-Jaramillo, Silvio
AU - Castillo, Renan C.
AU - Reynolds, Mary Jane
N1 - Funding Information:
We thank: Mary Lou Clements-Mann, Patricia Fast, and Barney Graham for support and helpful discussion; Robert Siciliano's laboratory for CTL assays; and Yaikah Jeng for valued technical assistance. This work was supported by AVEU contract #NO-1-AI-45207.
PY - 1997/7/26
Y1 - 1997/7/26
N2 - Background: In the USA, more than 2000 volunteers have received one or more experimental HIV-1 vaccines in phase I and II clinical trials, and there have been breakthrough HIV-1 infections among participants receiving vaccine and placebo. Serological diagnosis of new HIV-1 infections in vaccine-trial participants will become increasingly complicated as more viral components are used in vaccines. Recognition of this problem has led to a reliance on viral-genome measurement to distinguish vaccine-induced immunity from HIV-1 infection. Currently, quantitative RNA measurement is expensive, prone to contamination, and reliable only in laboratories certified by manufacturers or that have quality-control programmes. Methods: A high-risk vaccinee presented after an acute febrile episode and was tested for HIV-1 infection by reverse transcriptase (RT) PCR of viral RNA. Further extensive tests were required to clarify the HIV-1 infection and immune status of the vaccinee, including repeat RT-PCR, nested DNA PCR, western blot, lymphoproliferation assay, cytotoxic-T-cell lysis, CD8-depleted co-culture, and HIV-1 challenge culture. Findings: Initial testing of plasma by RNA RT-PCR was reported as positive. This result was not confirmed by viral cultures, nested DNA PCR, western blot, or EIA. Additional RNA RT-PCR assays gave positive results from earlier occasions in the vaccine trial. Eventually, testing of all previously reactive samples by RNA RT-PCR was repeated in a quality-controlled laboratory, and confirmed the negative HIV-1 status of the individual. Interpretation: This case report exemplifies the difficulties with use of viral-genome measurement as a screening test to diagnose HIV-1 infection, particularly in individuals who have ever participated in HIV-1 vaccine trials. Monitoring of large numbers of phase III vaccinees by RNA RT-PCR will not be feasible. The design of efficacy trials for new vaccines should be in parallel with development of antibody-based diagnostic tests that are capable of differentiating between immunisation and true HIV-1 infection.
AB - Background: In the USA, more than 2000 volunteers have received one or more experimental HIV-1 vaccines in phase I and II clinical trials, and there have been breakthrough HIV-1 infections among participants receiving vaccine and placebo. Serological diagnosis of new HIV-1 infections in vaccine-trial participants will become increasingly complicated as more viral components are used in vaccines. Recognition of this problem has led to a reliance on viral-genome measurement to distinguish vaccine-induced immunity from HIV-1 infection. Currently, quantitative RNA measurement is expensive, prone to contamination, and reliable only in laboratories certified by manufacturers or that have quality-control programmes. Methods: A high-risk vaccinee presented after an acute febrile episode and was tested for HIV-1 infection by reverse transcriptase (RT) PCR of viral RNA. Further extensive tests were required to clarify the HIV-1 infection and immune status of the vaccinee, including repeat RT-PCR, nested DNA PCR, western blot, lymphoproliferation assay, cytotoxic-T-cell lysis, CD8-depleted co-culture, and HIV-1 challenge culture. Findings: Initial testing of plasma by RNA RT-PCR was reported as positive. This result was not confirmed by viral cultures, nested DNA PCR, western blot, or EIA. Additional RNA RT-PCR assays gave positive results from earlier occasions in the vaccine trial. Eventually, testing of all previously reactive samples by RNA RT-PCR was repeated in a quality-controlled laboratory, and confirmed the negative HIV-1 status of the individual. Interpretation: This case report exemplifies the difficulties with use of viral-genome measurement as a screening test to diagnose HIV-1 infection, particularly in individuals who have ever participated in HIV-1 vaccine trials. Monitoring of large numbers of phase III vaccinees by RNA RT-PCR will not be feasible. The design of efficacy trials for new vaccines should be in parallel with development of antibody-based diagnostic tests that are capable of differentiating between immunisation and true HIV-1 infection.
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U2 - 10.1016/S0140-6736(97)01500-6
DO - 10.1016/S0140-6736(97)01500-6
M3 - Article
C2 - 9242803
AN - SCOPUS:0030841163
SN - 0140-6736
VL - 350
SP - 256
EP - 259
JO - The Lancet
JF - The Lancet
IS - 9073
ER -