HPTN Requirements
HPTN research sites performing HIV-1 antibody testing for
HPTN protocols must validate each HIV antibody testing algorithm
that they intend to use for any HPTN study in which incident HIV
infection is the primary endpoint.
FDA approved HIV antibody tests are recommended especially
for HPTN protocols conducted under an IND, but regardless of which
HIV antibody tests are used, each site needs to validate the
sensitivity and specificity of the testing algorithm they will use
for HPTN protocols. This
validation is for the algorithm, so if the same algorithm is used
for multiple protocols, the validation need not be repeated for each
study. If different algorithms will be used for different protocols,
each algorithm needs to be validated.
The validation process requires testing specimens from 100
confirmed
HIV-infected individuals and 100 confirmed HIV-uninfected
individuals using an FDA approved kit along with the kit (or kits)
planned for use in a study. If serum or
whole blood (venous) will be used at the site for future testing
then serum or whole blood specimens must be tested. If whole blood
finger prick specimens will be tested, then the assays will need to
be performed using finger prick specimens obtained from confirmed
HIV infected and uninfected subjects. The person testing the
specimens for validation should be blinded as to the HIV status of
the specimens.
For example, if both the Abbott Determine and Ora-Quick
tests will be used on whole blood with resolution of discrepant
results by HIV-1 Western blot, then at least 100 HIV positive
samples and 100 HIV negative samples should be obtained, for which
the positives have been confirmed positive by Western blot or IFA
that is approved by the FDA or your country’s regulatory
authority. The negatives should be confirmed negative by an FDA
approved HIV EIA or by two FDA approved rapid HIV tests. The final
result of the testing
algorithm should then be compared to the positive or negative result
of the reference test (i.e., Western blot if positive or EIA if
negative).
If testing reveals one or fewer false-positive or
false-negative results, then the testing algorithm has been
validated and the testing algorithm is approved for use in HPTN
protocols. If testing results in more than one false-negative or
false-positive sample, then more specimens will need to be tested.
If it is later decided to use a different algorithm for a
study at the site, the validation process should be repeated, as
described, for that algorithm.
Each site should send a validation report to Estelle
Piwowar-Manning (epiwowa@jhmi.edu) describing the validation
process used and the results of the testing in terms of sensitivity
and specificity. Upon
review of this documentation, the NL will provide
written concurrence that the algorithm has been approved for use in
HPTN studies.
There may be unique circumstances at each site that require
clarification or modification
of
this validation process. Sites are encouraged to contact the NL for
further guidance and to provide the NL with the plan for completing
this requirement in advance of implementation to ensure that the
process to be undertaken is adequate If subjects have given consent
to be tested for HIV, additional consent should not be necessary.
Since this is a quality assurance activity, not a research
activity, IRB review is not required, at least in the United States.
|
