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Probability of a false-negative HIV antibody test result during the window period: a tool for pre- and post-test counselling


Abstract and Figures

Failure to understand the risk of false-negative HIV test results during the window period results in anxiety. Patients typically want accurate test results as soon as possible while clinicians prefer to wait until the probability of a false-negative is virtually nil. This review summarizes the median window periods for third-generation antibody and fourth-generation HIV tests and provides the probability of a false-negative result for various days post-exposure. Data were extracted from published seroconversion panels. A 10-day eclipse period was used to estimate days from infection to first detection of HIV RNA. Median (interquartile range) days to seroconversion were calculated and probabilities of a false-negative result at various time periods post-exposure are reported. The median (interquartile range) window period for third-generation tests was 22 days (19-25) and 18 days (16-24) for fourth-generation tests. The probability of a false-negative result is 0.01 at 80 days’ post-exposure for third-generation tests and at 42 days for fourth-generation tests. The table of probabilities of falsely-negative HIV test results may be useful during pre- and post-test HIV counselling to inform co-decision making regarding the ideal time to test for HIV.
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Review article
Probability of a false-negative HIV
antibody test result during the window
period: a tool for pre- and post-test
Darlene Taylor
, Monica Durigon
, Heather Davis
Chris Archibald
, Bernhard Konrad
, Daniel Coombs
Mark Gilbert
, Darrel Cook
, Mel Krajden
, Tom Wong
and Gina Ogilvie
Failure to understand the risk of false-negative HIV test results during the window period results in anxiety. Patients
typically want accurate test results as soon as possible while clinicians prefer to wait until the probability of a false-
negative is virtually nil. This review summarizes the median window periods for third-generation antibody and fourth-
generation HIV tests and provides the probability of a false-negative result for various days post-exposure. Data were
extracted from published seroconversion panels. A 10-day eclipse period was used to estimate days from infection to
first detection of HIV RNA. Median (interquartile range) days to seroconversion were calculated and probabilities of a
false-negative result at various time periods post-exposure are reported. The median (interquartile range) window
period for third-generation tests was 22 days (19–25) and 18 days (16–24) for fourth-generation tests. The probability
of a false-negative result is 0.01 at 80 days’ post-exposure for third-generation tests and at 42 days for fourth-generation
tests. The table of probabilities of falsely-negative HIV test results may be useful during pre- and post-test HIV counselling
to inform co-decision making regarding the ideal time to test for HIV.
HIV, AIDS, diagnosis, testing, seroconversion, HIV assays, window period, eclipse period, false-negative
Date received: 3 March 2014; accepted: 9 June 2014
Over 34 million people worldwide are estimated to be
living with HIV infection.
Detection of acute HIV is key
to reducing onward transmission as individuals are most
infectious at this phase.
Moreover, individuals who are
unaware of their HIV status have been shown to dispro-
portionately contribute to onward transmission.
test technologies, including assays that detect viral
RNA, p24 antigen, HIV antibodies and antibody/anti-
gen in combination are beneficial in that, collectively,
they diagnose HIV in acute and latent phases.
However, clinicians face challenges when they attempt
to provide accurate estimates of window periods (WPs),
i.e., the time between the infection and first detection of
during pre- and post-test counseling with clients.
For antibody-based tests, the WP is the time to first
detection of antibodies and leads to full seroconversion,
which is the serological confirmation of HIV infection
following a prior negative test. Time from infection to
the appearance of antibodies varies among individuals,
British Columbia Centre for Disease Control, Vancouver, BC, Canada
School of Population and Public Health, University of British Columbia,
Vancouver, BC, Canada
Alberta Health Services, Edmonton, AB, Canada
Public Health Agency of Canada, Ottawa, ON, Canada
BCCDC Public Health Microbiology and Reference Laboratory,
Vancouver, BC, Canada
Pathology and Laboratory Medicine, University of British Columbia,
Vancouver, BC, Canada
Family Practice, University of British Columiba, Vancouver, BC, Canada
Corresponding author:
Darlene Taylor, BC Centre for Disease Control, 655 W12th Ave.,
Vancouver, BC V5Z 4R4, Canada.
International Journal of STD & AIDS
2015, Vol. 26(4) 215–224
!The Author(s) 2014
Reprints and permissions:
DOI: 10.1177/0956462414542987
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and while seroconversion demonstrates a final diagnosis
of HIV, markers of infection such as RNA and p24 anti-
gen appear earlier. Figure 1 illustrates the appearance of
these markers leading up to seroconversion.
Early diagnosis after HIV exposure has potential
benefits to patients. Early treatment has been shown
to improve long-term outcomes
and can reduce the
likelihood of onward transmission, especially if strate-
gies, such as risk-behaviour counselling and/or early
treatment to reduce viral load, can be rapidly imple-
There is a utilitarian public health benefit
for adopting test technologies that provide accurate
results with minimal WP; however, from a clinical per-
spective it has become increasing difficult to counsel
clients about the optimal time to test after a risk
event, especially when clients are anxious to know the
earliest time they can test to confirm positivity, or the
longest time they have to wait to know with a fair
degree of certainty that they are indeed HIV-negative.
Research has shown that pre-test anxiety is high for
a large percentage of individuals testing for HIV which,
in some cases, results in denial of risk and test
Figure 1. Time to detection of HIV RNA, p24 antigen and antibody via various HIV assays.
216 International Journal of STD & AIDS 26(4)
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When these individuals decide to test, rec-
ommendations to ‘‘wait out’’ the WP can create further
anxiety related to fear of a positive result and the
accompanying HIV-related stigma.
People use the
words ‘nerve-wracking,’ ‘constant fear’, and ‘paranoid’
to describe their feelings while waiting for results
while waiting for the ‘appropriate’ time to present for a
test, even for people with low risk. Some people value
the time between the blood draw and receipt of results
because it allows them time to prepare for the outcome,
but research has also shown that HIV testers are pri-
marily concerned about speedy and accurate test
Moreover, client anxiety is magnified with
the ambiguity of an unconfirmed result caused by fal-
sely-reactive screen tests and/or indeterminate Western
blot (WB) tests. An indeterminate result occurs when a
reactive third- or fourth-generation test fails to be con-
firmed by a WB test or when persons are in the process
of HIV seroconversion. False antibody test reactivity
usually results from antibodies binding to non-HIV
components of the screening tests. The frequency of
false-positivity may range from 0.03 in a low incidence
setting such as China to 0.20 in an American low inci-
dence population
to 14% in high incidence settings in
Supplemental tests conducted with a new
blood sample are recommended to confirm the diagno-
Indeterminate results that occur during early sero-
conversion are usually resolved with follow-up WB
and/or HIV RNA testing. Follow-up testing will also
be required if the individual tests non-reactive, but is
within the WP for the screening test.
information is often delivered to patients with indeter-
minate results, raising even further angst.
it is incumbent upon clinicians to be able to pro-
vide accurate information about the probability of
an accurate test result given an estimated date of
Determining the WP length, which varies due to the
dynamic and heterogeneous nature of viral and host
responses, has preoccupied researchers for dec-
Busch et al.
identified six major elements
relevant to determining WP lengths: (1) patients with
symptoms of acute HIV infection, (2) patients with pri-
mary HIV infection with a known date of exposure, (3)
recipients of infected blood products, (4) seroconvert-
ing plasma donors who provide serial blood samples,
(5) serial blood samples from high-risk cohort studies
and (6) animal models. The current literature reports
average WPs (variances are rarely provided) or ranges
of days after infection that any given assay will detect
HIV infection.
Seroconversion panels from plasma
donors are likely the most informative source of WP
data for different tests, due to the frequency of speci-
men collection before and after HIV RNA is identified
during screening, often at Fiebig Stage I.
The number
of days from infection to detection of viraemia is
known as the eclipse phase and is crucial to calculating
an assay’s overall WP. Markov models have been used
to describe the progress through the various stages of
HIV in an infected person.
Markov modelling
examines a collection of states (like various stages of
HIV infection) and determines how HIV infection tran-
sitions from the state of eclipse period state through to
the state to the latent infection state, given statistical
information about the way that these state transitions
are set up.
Modeling has estimated the eclipse period
to be 10 days in duration.
The purpose of our study was to use knowledge of
the eclipse period and data from commercial and litera-
ture-reported seroconversion panels to calculate the
WPs for third- and fourth-generation HIV tests and
to provide a table reflecting the probability of a nega-
tive test result during the WP among known HIV-
infected individuals.
Third- and fourth-generation HIV test data were
extracted from publicly available data sheets from
HIV-positive seroconversion reference panels from
Boston Biomedica Inc/Seracare (BBI) (West
Bridgewater, MA) dated April 1981–October 2006
and ZeptoMetrix Corporation (Buffalo New York)
dated May 1996–December 2006.
These manufac-
turer panels include third-generation antibody, fourth-
generation antigen/antibody, p24 antigen, polymerase
chain reaction (PCR), and WB results from serial
bleeds of plasma donors on repeated days before and
after seroconversion. Each panel represents data from
one HIV-infected individual and consists of results
from a variety of assays. Panels were included in our
analysis only if they provided a third-generation or
fourth-generation test result and a PCR test result, and
are currently in use for HIV diagnosis. Results of rapid
point-of-care tests were excluded from the analysis.
Manuscripts with seroconversion data not already
included in the BBI and ZeptoMetric panels were iden-
tified by a systematic review of the literature. We
searched Medline and Embase databases for articles
published between 1990 and 2010. Both databases
were searched using the following terms: HIV infection;
HIV diagnosis; HIV screening; immunoassay; HIV
diagnostic test; serology; nucleic acid assay; nucleic
acid amplification test (NAAT); HIV antibody tests;
enzyme-linked immunosorbent assay; enzyme immuno-
assay (EIA); PCR; western blot; HIV-negative; acute
infection; WP; reverse transcription (RT)-PCR amplifi-
cation assay; pooled HIV RNA; HIV RNA; HIV
NAAT; NAAT; HIV NAT; NAT; diagnostic tests,
diagnostic testing, and screening. Titles and abstracts
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were reviewed by two reviewers (DT and MD) to deter-
mine if they should be included in the analysis, dupli-
cates were removed and data including date of last
negative and date of first positive for third-generation
fourth-generation and PCR/NAAT tests were
Third- and fourth-generation test results are typic-
ally expressed as signal to cutoff (s/co) ratios. Ratios
1.0 are considered reactive. The date of each blood
draw, associated s/co (or positive/negative status) and
name of assay were extracted for each donor. The
number of days between blood draws was calculated
and the date of first positive PCR/NAAT test for
each assay was noted. The number of days from the
positive PCR/NAAT test to the first positive third- or
fourth-generation test for each panel was calculated,
and added to an estimated eclipse period to represent
the number of days from infection to first positive
third- or fourth-generation results.
In order to estimate the eclipse period, which is the
time from infection to detection of virus by PCR/
NAAT test, the information assembled by this system-
atic review was used to parameterize a stochastic model
of early HIV infection.
This new methodology, based
on a continuous time branching process of infection,
conditioned on survival of the virus, allows the dur-
ation of the HIV WP to be estimated subject to a
small number of well-defined assumptions. The model
confirms the widely held hypothesis that typical eclipse
periods are in the range of 8–14 days, consistent with
Fiebig’s estimate of 10 days.
Therefore, we used an
eclipse period of 10 days to calculate the probability of
a negative test at a given time post-exposure in an HIV-
positive individual. WPs for each third-generation and
Figure 2. The number of individual assay results included and excluded for panels provided by manufacturers and panels that were
retrieved from the literature.
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fourth-generation HIV assay were calculated as fol-
lows: 10 days þnumber of days between the first posi-
tive PCR test and the first positive third- or fourth-
generation test.
Frequency analysis was conducted to describe the
estimated WP for both third- and fourth-generation
tests. These data were then used to draw a Kaplan-
Meier curve and the cumulative proportion of tests
remaining negative was used to calculate the condi-
tional probability of a negative test result at various
time intervals.
The study received ethical approval from the
University of British Columbia Clinical Research
Ethics Board (H11-01197).
Third-generation antibody tests
Data from 136 seroconversion panels were identified
consisting of 1361 individual assay results. A total of
780 individual assay results were excluded because they
did not have both a PCR and third-generation results
(n¼436), they used an assay that was no longer in rou-
tine use (n¼61), the donor did not seroconvert prior to
cessation of donating plasma (n¼49), the length of
time between blood draws resulted in the PCR being
positive on the same day as the antibody test (n¼41),
and duplicate records (n¼193). Panels that had the
same panel ID number, the same assay and the same
manufacturer were considered duplicates. Figure 2 dis-
plays the number of individual assay results included
and excluded for panels provided by manufacturers and
panels that were retrieved from the literature. Due to
the anonymous nature of the samples, no demographic
or risk factor information is known.
WPs ranged from 12 to 99 days. Overall the mean
(SD) WP for all assays is 25.04 (13.1) days (manufac-
turer: 22.16 [7.1]; literature: 26.68 [16.9]). The median
WP is 22 days (interquartile range [IQR]: 19–25)
(manufacturer: 21; IQR: 19–24); literature: 24; IQR:
19–28). Table 1 displays the probability of a negative
test result for a third-generation HIV test at various
time points in an HIV-positive individual. Figure 3 dis-
plays the distribution of WP days for third-generation
EIA tests. Figure 4 displays time to seroconversion
using a Kaplan-Meier curve.
Fourth-generation antibody/antigen tests
Data from 211 seroconversion panels were identified
consisting of 1229 individual assay results. A total of
569 individual assay results were excluded because they
did not have both a PCR and a fourth-generation test
result (n¼415), they used an assay that was no longer
in routine use (n¼6), the donor did not seroconvert
prior to cessation of donating plasma (n¼21), and
the length of time between blood draws resulted in
the PCR being positive on the same day (n¼127).
Figure 5 displays the number of individual assay results
included and excluded for panels provided by a manu-
facturer and panels that were retrieved from the
WPs ranged from 11 to 43 days. Overall the mean
(SD) WP for all assays is 20.45 (7.0) days (manufac-
turer: 18.4 [4.0]; literature: 20.76 [7.2]). The median
WP is 18 days (IQR: 16–24) (manufacturer: 17,
Table 1. Probability of a negative test result for a third- and
fourth-generation HIV test at various time points in an HIV-
positive individual.
Time since
infection (days)
Cumulative conditional probability
(99% confidence interval)
Third generation Fourth generation
0–9 1.00 (.991–1.00) 1.00 (.992–1.00)
10 1.00 (.991–1.00) 0.99 (.968–.993)
12 0.99 (.971–.996) 0.86 (.820–.890)
14 0.95 (.920–.968) 0.79 (.748–.829)
16 0.80 (.751–.837) 0.51 (.463–.562)
18 0.70 (.650–.747) 0.40 (.356–.453)
20 0.56 (.503–.609) 0.35 (.305–.400)
22 0.46 (.403–.509) 0.31 (.264–.355)
24 0.23 (.187–.277) 0.20 (.159–.238)
26 0.22 (.174–.262) 0.18 (.141–.216)
28 0.13 (.097–.169) 0.08 (.058–.113)
30 0.09 (.062–.122) 0.08 (.054–.108)
32 0.09 (.062–.122) 0.07 (.048–.099)
34 0.07 (.049–.104) 0.05 (.034–.078)
40 0.05 (.038–.088) 0.05 (.034–.078)
42 0.05 (.038–.088) 0.01 (.005–.027)
45 0.05 (.038–.088) 0.01 (.005–.027)
50 0.05 (.028–.074) 0.00
55 0.04 (.026–.070)
60 0.04 (.020–.061)
65 0.04 (.020–.061)
70 0.03 (.014–.050)
75 0.03 (.014–.050)
80 0.03 (.014–.050)
85 0.01 (.002–.022)
90 0.01 (.002–.022)
95 0.01 (.002–.022)
99 0.00
These numbers are based on a sample of seroconversion panels.
However, theoretically, the probability of a negative test result in an
HIV-positive person never reaches zero.
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Figure 4. Time to seroconversion for third- and fourth-generation tests using a Kaplan-Meier curve.
Figure 3. The distribution of WP days for third-generation antibody tests.
220 International Journal of STD & AIDS 26(4)
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IQR: 16–20.5; literature: 18, IQR: 16–25). Table 1 dis-
plays the conditional probability of a negative test
result in an HIV-positive individual for a third- and
fourth-generation HIV test at various time points fol-
lowing an HIV exposure. Figure 4 displays Kaplan-
Meier curves with the time to seroconversion based
on a third- and fourth-generation anti-HIV assays.
Figure 6 displays the distribution of WP days for
fourth-generation tests.
This study provides estimates for the probability of a
false-negative third- and/or fourth-generation EIA HIV
test at various time intervals after HIV infection. The
overall median WPs (22 days for third generation; 18
for fourth generation) are consistent with what others
have reported, mainly through mathematical modeling
which estimates the eclipse period.
Other studies
using dates from the onset of seroconversion illness
symptoms report that third-generation assays become
positive approximately 13 days after the onset of symp-
toms with fourth-generation tests becoming positive in
as little as two days after symptom onset.
these studies do not take into consideration the eclipse
period prior to the onset of symptoms which can be 1–2
In addition, studies examining the WP from
recipients of HIV-infected blood products report a two-
week eclipse period.
The reported mean/median WPs for third- and
fourth-generation tests vary. Older studies of third-gen-
eration tests estimated WPs of 45 days.
The 23-day
reduction in the WP to 22 days likely reflects improve-
ments in the selection of HIV antigen targets as well as
improvements in antibody test signal amplification che-
mistries. However, it may also be due to the methods
and assumptions used to determine the actual date of
seroconversion. Many researchers model estimates of
Figure 5. The number of individual fourth-generation results included and excluded for panels provided by a manufacturer and
panels that were retrieved from the literature.
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the date of seroconversion using the date of last nega-
tive and positive test under the assumption that the
data are normally distributed. However, our analysis
suggests that the time to seroconversion between
blood draws is not normally distributed, in part
because there is an eclipse phase prior to which HIV
RNA is not detected and during this time period, the
antibody response is not typically elicited. Therefore,
we have used a median value which likely provides a
more accurate estimate of the WPs. The median WP for
the fourth-generation assays was four days shorter than
the third-generation assays which results from the
detection of p24 by the fourth-generation assay and is
consistent with earlier findings.
We have combined information from previous math-
ematical modelling of data from known seroconverters
to not only confirm median WPs reported by others,
but also to provide the probability of a false-negative
test result at various points after exposure, which may
be useful in pre- and post-test counselling. For example,
if a patient requests an HIV test 16 days after a high-
risk sexual encounter (e.g., unprotected anal inter-
course), by using our instrument, a clinician might
advise the person that if they are indeed infected there
is an 80% chance a third-generation test would be
negative or a 51% chance that a fourth-generation
test would be negative if they had, in fact, become
infected. In contrast, the clinician can advise that
after 99 days, a third-generation test has essentially a
0% chance of giving a false negative result or after 50
days for a fourth-generation test. This is the first time,
to our knowledge, that such information has been
reported. However, clinicians using this instrument
should understand that these probabilities do not take
into account inter-patient variability in the length of the
eclipse phase and the antibody response. Mathematical
modelling based on the data presented here suggests
that the majority of patients have an eclipse phase dur-
ation in the range of 6–16 days, encompassing the
simple estimate of 10 days that we used to construct
the table of probabilities. However, it is entirely pos-
sible that a small number of patients will have atypical
responses leading to much longer eclipse phases. This
new pre-test counselling instrument may help reduce
anxiety for clients and promote co-decision making
with their health care provider regarding the best time
to undergo testing for HIV.
Results of rapid point-of-care tests were excluded
from analysis so we are unable to estimate the WPs
for these assays. It is expected that rapid assay WPs
are likely to be somewhat longer than for laboratory-
based tests.
Clinicians who offer point-of-care tests
to clients should include this potential limitation in
their pre- and post-test counseling.
This review synthesized data from third- and fourth-
generation HIV tests conducted between 1981 and
2006. Current fourth-generation assays have likely
Figure 6. The distribution of WP days for fourth-generation tests.
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improved since 2006 but it is not possible to determine
what assay modifications may have been made by
manufacturers over time, as this information is not
reported. Specifically, the Abbott fourth-generation
ARCHITECT HIV Ag/Ab Combo assay has been
reported to identify HIV infection within two weeks
compared to the median of 18 days we reported.
Practitioners who counsel patients who have been
tested with a fourth-generation test should keep this
in mind when using our table of probabilities.
It is important to recognize that WPs are estimates
and that there is considerable individual variation with
some individuals having shorter or longer than average
WPs. Pollett et al.’s
example of a 21-month time-to
seroconversion in a 30-year-old woman is an excellent
example of how variable WPs can be. Therefore, prac-
titioners using the table of probabilities to counsel their
patients should do so with this caveat.
The authors recognize that the instrument we report
has not been clinically validated. Further research is
required to confirm the validity and reproducibility of
the instrument, as well as its acceptability to clinicians
and clients. In addition, individuals who donated serum
for the commercial seroconversion panels were paid
donors. We do not know the socio-demographic char-
acteristics of these donors, but it is possible that they
may not be representative of the general population.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
The authors disclosed receipt of the following financial sup-
port for the research, authorship, and/or publication of this
article: This work was supported by the Canadian Institutes
for Health Research [FRN: 108451].
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... In the case of recent exposure, the tests should be repeated at 45-50 days (according to the test to be used) from the time of exposure. 83,[87][88][89][102][103][104] (1 B) • Individuals with a high-risk exposure to HIV should not be fully reassured until the test process is completed. 105 (2 D) • When using fourth-generation assays, individuals who have a negative screening test after 45 days of exposure may be recalled for a follow-up in specific circumstances, for example if postexposure prophylaxis (PEP) was given for any reason (e.g. ...
Testing for HIV is critical for early diagnosis of HIV infection, providing long‐term good health for the individual and prevention of onward transmission if antiretroviral treatment is initiated early. The main purpose of the 2021 European Guideline on HIV Testing in Genito‐Urinary Settings is to provide advice on testing for HIV infection in individuals aged 16 years and older who present to sexually transmitted infection, genito‐urinary or dermato‐venereology clinics across Europe. The guideline presents the details of best practice and offers practical guidance to clinicians and laboratories to identify and offer HIV testing to appropriate patient groups.
... Taylor et al. [75] reviewed data from commercial and literature-reported seroconversion panels to calculate the window period for third-and fourth-generation tests and calculate the probability of a false-negative test result during the window period. For third-generation tests the cumulative probability of a false-negative HIV test result was 5%, 1% and 0% post-exposure, respectively, and for fourth-generation tests the corresponding intervals were 34, 42 and 50 days. ...
... We have provided instances from the different laboratory disciplines, but of course this list is far from comprehensive. [12][13][14] There are various clinical scenarios in which an unexpected laboratory result may occur, including: ...
Approximately 70% of all healthcare decisions affecting diagnosis and treatment involve the use of tests performed within pathology laboratories. The utilisation of diagnostic laboratory services continues to increase, with growth both in volume of tests requested, as well as in the breadth of test repertoire. Every year in the United Kingdom, approximately 1 billion tests are run in hospital laboratories, equivalent to 14 tests per person. Fifty million tests are requested in primary care. Accordingly, there is an inevitable increase in the number of unexpected laboratory results which clinicians review. This is an important, and potentially time-consuming, issue, which we considered to merit a more detailed discussion. Unexpected laboratory results may be critical or non-critical in nature. They may be absolutely genuine, reflecting a clinical change in the patient's condition, a differential diagnosis not previously considered, or an additional test specifically added by the laboratory. However, such results may also occur due to a variety of different circumstances, including much more rarely laboratory error. As there is little published evidence or guidance available, herein we discuss aspects of the clinical approach for physicians after receiving an unexpected laboratory test result.
... Após a realização dos TR HIV no CRT -DST/Aids, as 1.141 amostras de soro foram50 que demonstram o tempo de detecção da infecção em diferentes ensaios para HIV, revelando que ensaios de quarta geração e testes rápidos (terceira geração) levam de duas a três semanas para detectar os anticorpos, enquanto os ensaios que empregam a metodologia de WB podem levar um tempo superior.Em relação às amostras com resultados não reagentes no TR (911), quando avaliadas no CHIV, 907 apresentaram-se como não reagentes e quatro foram reagentes. Destas quatro amostras, uma (25%) apresentou-se como não reagente no ensaio confirmatório (IBR), devido à ausência de bandas, sendo nesta amostra o resultado de CHIV próximo ao valor de cut off (1,05/1,00), mantendo-se este valor mesmo após a repetição do ensaio com a amostra analisada em duplicata. ...
Experiment Findings
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A realização de testes diagnósticos de HIV consiste no primeiro passo para identificar indivíduos infectados para a assistência e cuidados, sendo sua acurácia elemento chave neste processo de Vigilância em Saúde. A identificação laboratorial da infecção pelo HIV baseia-se principalmente na detecção de anticorpos específicos em amostras biológicas coletadas de pacientes e/ou de indivíduos com comportamento de risco em adquirir esta infecção. O objetivo principal deste trabalho foi avaliar a comparabilidade do resultado de testes rápidos (TR) utilizados para o diagnóstico de HIV em relação a testes laboratoriais convencionais em amostras de sangue de população de travestis e mulheres transexuais da cidade de São Paulo, provenientes de um estudo de coorte transnacional entre Brasil e Estados Unidos. No Centro de Referência e Tratamento de Doenças Sexualmente Transmissíveis/Aids, 1.141 amostras de sangue foram avaliadas nos TR, e, posteriormente, foram encaminhadas ao Instituto Adolfo Lutz (IAL) para a realização dos testes laboratoriais convencionais (ensaio de quimioluminescência, imunoblot rápido e teste molecular), no período de setembro a dezembro de 2018. As 230 amostras com resultado reagente no TR HIV apresentaram-se também positivas nos ensaios laboratoriais convencionais. No entanto, das 911 amostras com resultado de TR não reagente, três (0,3%) apresentaram-se reagentes nos testes convencionais para HIV. Dessa forma, o estudo mostrou elevada concordância entre testes rápidos e convencionais, apresentando algumas limitações do método único do TR, em função de falha técnica ou humana.
... In the serum evaluation with a new sample (third sample) of that person, it was observed that the reactivity profile was present in all bands of the used RIB (gp160, gp120, gp41, p24); this demonstrates that the appearance of a marker in circulation depends on the infection stage (23,24) . This case presents one of the situations that can be more frequent with the improved identification and incorporation of people living with HIV, having as consequence the increased proportion of recent cases among the total of infected subjects. ...
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Introdução:Muitos fatores podem impactar no desempenho dos testes para diagnóstico da infecção pelo vírus da imunodeficiência humana (HIV), comprometendo os resultados de pesquisas populacionais. Objetivo: O objetivo deste estudo foi avaliar o desempenho dos testes rápidos (TR) – point-of-care – utilizados para o diagnóstico do HIV em relação aos ensaios convencionais em amostras de sangue da população de travestis e mulheres transexuais da cidade de São Paulo, São Paulo, Brasil. Métodos: Ao Instituto Adolfo Lutz (IAL), 1.385 amostras com os resultados dos TR do HIV foram encaminhadas para serem avaliadas por testes laboratoriais convencionais. Resultados: Das 240 (17,3%) amostras que apresentaram resultado reagente nos TR, a positividade para HIV foi confirmada em 100% por testes laboratoriais convencionais. Entretanto, das 1.145 (82,7%) amostras com resultado de TR não reagente avaliadas, três (0,3%) apresentaram-se reagentes e uma (0,1%), indeterminada para HIV. Embora uma porcentagem de resultados falso-negativos nos TR tenha sido encontrada, os testes realizados em campo possuem alta taxa de confirmação quando comparados com os testes sorológicos. Conclusão: Os dados deste estudo ressaltam a importância da adoção de ferramentas de gestão eficazes para assegurar a qualidade do diagnóstico da infecção por HIV.
... Esse estigma é observado no Brasil na proibição legal de doação de sangue por homens que fizeram sexo com homens nos últimos 12 meses, regulamentada pela Portaria nº 158, de 4 de fevereiro de 2016 47 . Essa legislação é discriminatória na medida em que existem no mercado testes laboratoriais de quarta geração que diminuem o tempo de janela imunológica para cerca de 18 dias (intervalo interquartílico de 16 a 24 dias) 48 . Além disso, a comunidade científica tem debatido mudanças no processo de segurança hemoterápica a partir da identificação clínica de práticas sexuais, e não da rotulação de grupos populacionais 49 . ...
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Introduction: Discrimination based on sexual orientation can influence vulnerability to HIV, increasing exposure to risky sexual behavior among men who have sex with men (MSM). Objectives: To analyze data using latent class analysis (LCA) to identify groups of individuals with specific patterns of discrimination based on sexual orientation (DSO). Methods: Cross-sectional study using respondent-driven sampling in 12 Brazilian cities in 2016. LCA was used to characterize discrimination among MSM based on 13 variables in the survey questionnaire. The proportions of men reporting DSO and other variables of interest were estimated using Gile's Successive Sampling estimator. Results: Most MSM were young, single, had a religion, had a high school or college degree, black or brown skin color, and socioeconomic status classified as average. More than half of the participants reported that they had been discriminated against during the last 12 months due to their sexual orientation (65%), more than a third said they had felt afraid of walking in public places during the past 12 months, and about one-fifth of participants reported having been victims of physical or sexual assault due to DSO. DSO was classified into four latent classes: "very high", "high", "moderate" and "low", with estimates of 2.2%, 16.4%, 35.1%, and 46.19%, respectively. Conclusion: We observed a high proportion of discrimination against MSM in this study. The use of LCA differentiated parsimoniously classes of discrimination.
... Due to lower concentrations of antibodies, oral fluid HIVST cannot detect early stages of an HIV infection (25). Given these limitations, oral fluid HIVST (2nd generation) is estimated to have a 55-day window period (26); in contrast, window periods for blood-based markers are about 18 days for tests that assess p24 antigen (4th generation) and about 22 days for antibody only (3rd generation) tests (27). ...
HIV self-testing (HIVST) provides an at-home option to counter the barriers that patients face with testing performed in a healthcare setting. HIVST has gradually increased in popularity in a time when social media and tech-based solutions are preferred. In this paper, we consider the aspects of self-testing that merit its integration into HIV testing and prevention systems in the United States. Several elements favor self-testing for large-scale implementation including ease of use, convenience, potential for integration with mobile health (mHealth), and availability for various modes of distribution. HIVST has demonstrated the ability to reach at-risk individuals who might otherwise rarely test. The paradigm of self-testing, however, introduces new challenges such as decreased performance compared to testing performed in a healthcare setting, the role of counseling for receiving test results, and difficulty of linking to care. After discussing the performance of oral fluid vs. blood-based HIVST, we review data regarding acceptability of HIVST, offer insights into counseling and linkage to care for HIVST, and provide examples of novel applications of and future research directions for HIVST.
... 18 In adults, antibody-based tests have limitations due to a long window period, which may lead to failure in detecting recent HIV infection. 19 However, this is less of a concern among older children and younger adolescents who, if infected, are likely to have long-standing HIV, acquired perinatally. ...
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Background: Gaps persist in HIV testing for children who were not tested in prevention of mother-to-child HIV transmission programs. Oral mucosal transudate rapid HIV tests (OMT) have been shown to be highly sensitive in adults but their performance has not been established in children. Methods: ART-naïve children aged 18 months to 18 years in Kenya and Zimbabwe were tested for HIV using rapid OraQuick ADVANCE Rapid HIV-1/2 Antibody test on oral fluids (OMT) and blood-based rapid diagnostic testing (BBT). BBT followed Kenyan and Zimbabwean national algorithms. Sensitivity and specificity were calculated using the national algorithms as the reference standard. Results: A total of 1,776 children were enrolled; median age was 7.3 years (IQR: 4.7, 11.6). Among 71 children positive by BBT, 71 were positive by OMT (sensitivity: 100% [97.5%CI: 94.9-100%]). Among the 1,705 children negative by BBT, 1,703 were negative by OMT (specificity: 99.9% [95%CI: 99.6-100.0%]). Due to discrepant BBT and OMT results, 2 children who initially tested BBT negative and OMT positive were subsequently confirmed positive within 1 week by further tests. Excluding these 2 children, the sensitivity and specificity of OMT compared to BBT were each 100% (97.5%CI: 94.9-100% and 99.8-100%, respectively). Conclusions: Compared to national algorithms, OMT did not miss any HIV-positive children. These data suggest that OMTs are valid in this age range. Future research should explore the acceptability and uptake of OMT by caregivers and health workers to increase pediatric HIV testing coverage.
... The risk of an infant being infected with HIV during pregnancy, delivery or breastfeeding can be reduced to 5% or less if the mother is on antiretroviral treatment (ART). 1 The highest mortality in an infant who has acquired HIV is between the ages of 6 weeks to 4 months; therefore, early infant diagnosis is imperative in identifying the status of the infant for early introduction of treatment. 1,2,3,4 A South African trial conducted in HIV-positive infants showed improved short-term neurodevelopmental outcomes because of early initiation of ART, in comparison to infants for whom treatment was delayed. 5 Violari et al. 6 found that infant mortality was reduced by 76% and HIV progression by 75% when infants infected with HIV were diagnosed and placed on ART before 12 weeks of age. ...
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Background: Birth polymerase chain reaction (PCR) testing improves early detection of HIV and allows for early treatment initiation. National guidelines exist, but it is unknown whether these are being implemented correctly. Objectives: To determine whether HIV-exposed infants at the Mangaung University Community Partnership Programme Community Health Centre (MUCPP CHC) received PCR tests at birth, if HIV-positive infants were initiated on treatment, if follow-up dates were scheduled and the percentage of mothers or caregivers who returned to collect the results. Methods: The study was a retrospective descriptive file audit (1304 files) of births from 01 January to 31 December 2016 at MUCPP CHC. The study sample was 428 infants born to HIV-positive mothers. The birth register was used to collect the infants’ HIV PCR test barcodes. The birth and 10-week PCR results were retrieved from an electronic database at the Virology Department, University of the Free State. Results: In total, 375 infants received a birth PCR test (87.6%) of which 4 (1.1%) tested HIV positive and 327 (87.2%) negative. Follow-up tests were not scheduled. However, 145 (44.3%) HIV-negative infants returned for a 10-week test. Irrespective of the PCR birth result, 157 (36.7%) infants were brought for a 10-week follow-up test at which time 3 (1.9%) tested positive and 151 (96.2%) negative. Conclusion: The majority of HIV-exposed infants received a PCR test at birth; however, the clinic is below the national target (90%) for HIV testing. A record-keeping system of infants’ visits does not exist at MUCPP CHC, making it impossible to determine whether HIV-positive infants were started on antiretroviral treatment.
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Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.
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Although rapid HIV tests increase the number of persons who are aware of their HIV status, they may fail to detect early HIV infection. To evaluate the sensitivity for early HIV infection of several rapid tests and third- and fourth-generation assays compared with nucleic acid amplification testing (NAAT). Sensitivity for early HIV infection was evaluated using 62 NAAT-positive/WB-negative or indeterminate specimens from the CDC Acute HIV Infection study. Specimens underwent third-generation testing with Genetic Systems 1/2+O(®) and rapid testing with Multispot HIV-1/HIV-2. A subset was also tested with four FDA-approved rapid tests and Determine HIV-1 Antigen/Antibody Rapid Test(®) and Architect HIV Antigen/Antibody Combo(®), both fourth-generation tests. Of 99,111 specimens screened from April 2006 to March 2008, 62 met the definition for early HIV infection (60 NAAT-positive/seronegative and 2 NAAT-positive/Western blot indeterminate). Third-generation testing correctly detected antibody in 34 specimens (55%; 95% confidence interval (CI): 42-67); Multispot detected antibody in 16 (26%; 95% CI: 16-38). Of the 62 specimens, 33 (53%) had sufficient quantity for further testing. Rapid test sensitivities for early HIV infection ranged from 22-33% compared with 55-57% for the third-generation assay and 76-88% for the fourth-generation tests. Many rapid HIV tests failed to detect half of the early HIV infection cases in whom antibody was present. Programs that screen high-incidence populations with rapid tests should consider supplemental testing with NAAT or other antigen-based tests. These data support the need for more sensitive antigen-based point-of-care screening tests for early HIV infection.
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Differentiating HIV-1 from HIV-2 poses another challenge.Almost all screening assays now incorporate antigens to detectboth HIV-1 and HIV-2, but because of cross-reactivity, the HIV-1Western blot is often positive in patients with HIV-2, and no HIV-2confirmatory test is currently approved by the U.S. Food and DrugAdministration (FDA).
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We compared the INSTI(TM) HIV-1 Antibody Point-of-Care (POC) Test to laboratory-based tests for detection of early sero-conversion (i.e. acute) HIV infections. Fifty-three (53) individuals with early HIV infection, (i.e. 3(rd) generation anti-HIV EIA non-reactive or reactive, HIV-1 Western Blot non-reactive or indeterminate and HIV-1 p24 antigen reactive) were tested by INSTI(TM). The INSTI(TM) test was reactive for 34/49 (sensitivity 69.4%; 95% confidence interval 54.6-81.8%) early-infected individuals whose laboratory-based 3(rd) generation HIV EIA test was reactive. Four (4) were non-reactive by both the laboratory-based EIA and INSTI(TM )tests, but were p24 antigen reactive. The INSTI(TM )POC test performs well compared with other POC tests for the detection of early sero-conversion HIV infection, but it may miss 20% to 30% of those detected by laboratory-based 3(rd) generation anti-HIV tests. Both POC and laboratory-based anti-HIV tests will fail to detect a proportion of infected individuals in the first weeks after infection.
Objectives: The characterization of primary HIV infection by the analysis of serial plasma samples from newly infected persons using multiple standard viral assays. Design: A retrospective study involving two sets of archived samples from HIV-infected plasma donors. (A) 435 samples from 51 donors detected by anti-HIV enzyme immunoassays donated during 1984–1994; (B) 145 specimens from 44 donors detected by p24 antigen screening donated during 1996–1998. Setting: Two US plasma products companies. Main outcome measures: The timepoints of appearance of HIV-1 markers and viral load concentrations during primary HIV infection. Results: The pattern of sequential emergence of viral markers in the ‘A’ panels was highly consistent, allowing the definition and estimation of the duration of six sequential stages. From the ‘B’ panels, the viral load at p24 antigen seroconversion was estimated by regression analysis at 10 000 copies/ml (95% CI 2000–93 000) and the HIV replication rate at 0.35 log copies/ml/day, corresponding to a doubling time in the preseroconversion phase of 20.5 h (95% CI 18.2–23.4 h). Consequently, an RNA test with 50 copies/ml sensitivity would detect HIV infection approximately 7 days before a p24 antigen test, and 12 days before a sensitive anti-HIV test. Conclusion: The sequential emergence of assay reactivity allows the classification of primary HIV-1 infection into distinct laboratory stages, which may facilitate the diagnosis of recent infection and stratification of patients enrolled in clinical trials. Quantitative analysis of preseroconversion replication rates of HIV is useful for projecting the yield and predictive value of assays targeting primary HIV infection.
Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011. We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ≥ 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period. A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively. Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.
We report the case of a 30-year-old woman who failed to achieve diagnostic Western blot criteria for HIV-1 infection until 21 months after her initial presentation. This case highlights the importance of suspecting delayed HIV seroconversion in cases with persistently indeterminant Western blots.
HIV testing in non-health care settings is an effective strategy for increasing the proportion of persons aware of their infection. We conducted 21 focus groups with 186 past and potential clients in five U.S. cities to explore attitudes and experiences related to HIV counseling and testing in non-health care settings. Qualitative analysis yielded several key themes. HIV-related stigma and fear emerged as a main theme throughout the discussions. Knowing one's HIV status quickly and accurately was of primary importance; HIV prevention counseling was secondary. Participants prioritized a supportive, nonjudgmental environment with adequate privacy and confidentiality. Provision of immediate emotional support, medical information, and linkage services to HIV-infected clients were considered essential. Staff with HIV-specific skills to address clients' emotional and informational needs was considered a strength of non-health care testing programs. Frequently, however, participants compared non-health care settings unfavorably to health care settings regarding privacy, competency, confidentiality, and test accuracy. Recommendations for enhancing counseling and testing services in non-health care settings are discussed.