INFECTIOUS DISEASES
Preparing Public Health Laboratories for HIV Testing
in a PrEP Era
by Monica Parker, PhD, director, Bloodborne Viruses Laboratory, Wadsworth Center, New York State Department of Health
and Anne Gaynor, PhD, manager, HIV, Hepatitis, STD & TB Programs
In 2019, the US Department of Health and
Human Services launched an initiative
entitled “Ending the HIV Epidemic: A
Plan for America” which aims to end the
HIV epidemic in the United States within
10 years by implementing coordinated
actions in four key areas: prevention,
diagnosis, treatment and care. A central
component of HIV prevention strategy
involves increasing access to and use of
pre-exposure prophylaxis (PrEP). PrEP
consists of two antiretrovirals (ARVs),
tenofovir and emtricitabine, combined
into a single pill which is taken daily to
prevent HIV infection. Several clinical
trials have shown that PrEP significantly
reduces the risk of acquiring HIV
infection 1-3 and is recommended for high
risk, HIV-negative adults. 4,5
A Step Forward in HIV Prevention
Increasing the use of PrEP is expected to
enhance HIV prevention efforts, but may
also pose new challenges for laboratories
when interpreting HIV diagnostic test
results. HIV testing must be conducted
prior to initiating PrEP to document
HIV-negative status and is recommended
every three months during PrEP. 4,5 A
person could be incorrectly considered
eligible for PrEP if they became infected
concurrent with their initial diagnostic
evaluation, or if they were infected prior
to the evaluation but were tested within
the initial test window period. 6,7 HIV
infection during PrEP is extremely rare if
ARVs are taken consistently as prescribed,
but the risk of infection increases as
adherence decreases. 6,8,9 Therefore, people
can become infected after they begin PrEP,
especially if they are not taking ARVs as
prescribed.
If someone is HIV-infected and takes or
continues to take PrEP, it may affect the
typical progression of biological markers
of infection and lead to atypical results
from serologic and nucleic acid tests
used to monitor HIV status during PrEP.
30
LAB MATTERS Fall 2019
We have learned from studies in which
ARV treatment was initiated during
acute HIV-1 infection before antibodies
developed that seroconversion may be
delayed or not occur at all. 6,7 The most
profound effects on antibody development
were seen when ARV treatment was
initiated in patients at the earliest stage of
acute infection before p24 antigen could
be detected. 6 Delayed seroconversion
has also been shown to occur when PrEP
is continued after HIV-1 infection takes
place 11 because the two-drug combination
used for PrEP—while not as potent as the
regimens used to treat HIV-1 infection—
can substantially reduce HIV-1 replication.
Preparing for the Unusual
Laboratories that conduct HIV testing
on specimens collected from individuals
on PrEP may encounter unusual or
inconsistent test results. Serological
screening tests, including HIV antigen/
antibody (Ag/Ab) immunoassays, may
produce a low or borderline signal (just
above or just below the cut-off). In some
cases, successive specimens taken on
different days may fluctuate between
a reactive and non-reactive result.
HIV-1 RNA tests may also show weak
reactivity and, in some cases, viral RNA
may be suppressed below the detection
level leading to a false negative result.
Importantly, the APHL recommended
reporting language for HIV diagnostic
testing 10 may not be appropriate for
interpreting results from people on ARVs.
Since the number of people on PrEP is
likely to increase under the new initiative,
there are some actions that public health
laboratories should consider. It may be
helpful to include a disclaimer on all
negative or inconclusive test reports,
stating “Antiretroviral drugs taken for
treatment or prophylaxis may limit the
ability of diagnostic tests to detect HIV
infection.” Laboratories may also consider
adding a question to the test requisition
PublicHealthLabs
@APHL
APHL.org