M A J O R A R T I C L E
Detection of Acute HIV Infection: A Field
Evaluation of the Determine? HIV-1/2 Ag/Ab
Nora E. Rosenberg,1Gift Kamanga,5Sam Phiri,6Dominic Nsona,6Audrey Pettifor,1Sarah E. Rutstein,2
Deborah Kamwendo,5,3Irving F. Hoffman,3Maria Keating,5,aLillian B. Brown,1,3Beatrice Ndalama,5Susan A. Fiscus,6
Seth Congdon,5Myron S. Cohen,1,3,4and William C. Miller1,3
Departments of1Epidemiology,2Health Policy and Management,3Medicine, and4Microbiology and Immunology, University of North Carolina, Chapel
Hill; and the5UNC Project, Lilongwe, Malawi; and6Lighthouse Trust, Lilongwe, Malawi
(See the editorial commentary by Branson and Stekler, on pages 521–4.)
p24 antigen (Ag) or RNA. In the absence of antibodies, p24 antigen and RNA typically indicate acute HIV infection.
We conducted a field evaluation of the Determine? HIV-1/2 Ag/Ab Combo rapid test (Combo RT).
Methods. The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor
HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was
compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV
testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic
and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant
antibody results and in all center participants.
Results.Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV
infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983.
For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992.
Conclusions.Combo RT displayed excellent performance for detecting established HIV infection and poor
performance for detectingacute HIV infection.In thissetting, Combo RT is no more usefulthan currentalgorithms.
Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not
Point-of-care rapid tests for human immunodeficiency
virus (HIV) antibody (Ab) detection have facilitated the
scale-up of HIV counseling and testing throughout sub-
Saharan Africa [1, 2]. The sensitivity of these tests
approaches 100% for antibody detection [3, 4]. How-
ever, the tests cannot identify persons with acute HIV
infection who have not yet developed HIV-specific an-
tibodies [5–7]. Persons with acute HIV infection are
often hyperinfectious because of high viral loads [8–12].
Integrating acute HIV infection detection into HIV
testing algorithms would enable acutely infected persons
to learn their true HIV status, rather than being informed
that they were HIV seronegative. Identifying these per-
sons with acute HIV infection could enable intervention
to prevent transmission and early treatment, potentially
preserving immune function [13, 14].
Identification of acute HIV infection requires detection
of HIV nucleic acids or p24 antigens. Available assays
are laboratory based, resource intensive, and require
follow-up. HIV RNA polymerase chain reaction (PCR),
used for either individual or pooled samples, is the ref-
erence standard for detecting antibody-negative acute
HIV infection, but it is expensive and difficult to imple-
ment in resource-poor settings. HIV p24 antigen (Ag)
enzyme-linked immunosorbent assays (ELISAs) have
good performance characteristics compared with HIV
RNA PCR analysis, but they have been challenging to
Received 9 July 2011; accepted 23 September 2011; electronically published 29
aPresent affiliation: Weill Cornell Medical College, New York.
Presented in part: 18th Conference on Retroviruses and Opportunistic Infections,
Boston, Massachusetts, 27 February to 2 March 2011. Abstract 654.
Correspondence: Nora E. Rosenberg, MSPH, Department of Epidemiology,
UNC-CH, Campus Box7435, Chapel Hill,NC27599-7435 (firstname.lastname@example.org).
The Journal of Infectious Diseases
? The Author 2011. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
d JID 2012:205 (15 February)
d Rosenberg et al
implement on a wide scale. Fourth-generation HIV ELISAs detect
both antibodies and antigens [6, 15, 16] but do not distinguish
between the two and require venipuncture, a laboratory, and
patient follow-up, limiting routine use in most settings.
A rapid point-of-care test capable of distinguishing established
from acute HIV infection could improve the sensitivity of existing
algorithms and enable provision of acute HIV infection results in
real time . The Determine? HIV-1/2 Ag/Ab Combo (Combo
RT) is a point-of-care rapid test with separate indicators for HIV
antibodies and p24 antigen. The Combo RT was designed to
identify HIV earlier than other conventional rapid tests. The an-
tibody portion is reported to be analogous to the Determine?
HIV-1/2 antibody test, a widely used rapid test for HIV identifi-
cation. The antigen component of the test is intended to expand
the diagnostic spectrum to identify persons with circulating free
RT antigen was assessed using stored serum from commercial
seroconversion panels . For primary HIV samples in the pre-
or periseroconversion period, the reported sensitivity of the anti-
generation HIV ELISA as the reference standard. Specificity of the
antigen portion of the test was reported at 96.6%. The Combo RT
is currently commercially available outside the United States.
We conducted a field evaluation in Lilongwe, Malawi, to assess
the accuracy of the antigen portion of Combo RT to detect per-
sons with acute HIV infection. The Roche Monitor HIV RNA
PCR assay was used to identify persons with acute HIV infection
after routine HIV rapid test evaluation for established HIV in-
fection. We also performed an ‘‘ultrasensitive’’ heat-dissociated
assessed the antibody portion of Combo RT against a standard
rapid test antibody algorithm.
Participants and Procedures
Participants were recruited from the Kamuzu Central Hospital
Sexually Transmitted Infection Clinic and the Lighthouse Trust
HIV Testing and Counseling Center in Lilongwe, Malawi, bet-
ween October 2009 and June 2010. At both sites, patients were
eligible if they were $18 years old, and willing to provide up to
1200 lL of blood in microvette capillary tubes, and willing to
provide informed consent. In the HIV testing and counseling
center, all consenting persons presenting for HIV testing were
enrolled before standard opt-out HIV rapid testing. In the sex-
ually transmitted infection clinic, only patients with negative or
discordant HIV rapid test results at high risk for acute HIV
infection were invited to participate to minimize the number of
persons screened and maximize the likelihood of identifying
persons with acute HIV infection . Participants completed
an interviewer-administered questionnaire on demographics,
sexual behavior, and symptoms.
All personnel conducting the standard HIV rapid tests and the
Combo RT were highly experienced HIV counselors. Training in
the performance and interpretation of the Combo RT was con-
ducted at the initiation of the study. Procedures were reviewed
during weekly study meetings.All tests were performedaccording
to the manufacturer instructions, including reading results within
the specified time frame.
The Combo RT (Inverness Medical Japan) is an in vitro, visual
qualitative immunoassay for use with human serum, plasma or
a chase buffer. If antibodies are present, they bind to an antigen–
selenium colloid and recombinant antigen in the test strip to
form a line. If free p24 antigen is present, it binds to a bio-
tinylated anti-p24 antibody in the sample pad, and to selenium
colloid anti-p24 antibody and immobilized avidin in the test
strip to form a separate line.
Ultrasensitive HIV p24 Antigen
To determine whether p24 antigen was present, an ELISA
(Alliance HIV-1 p24; Perkin Elmer Life Sciences) was used with
additional steps of heat dissociation and signal amplification.
Specimens were lysed, boiled to disrupt antigen–antibody
complexes, and enhanced with signal amplification (ELAST;
Perkin Elmer Life Sciences) [20, 21]. These steps have been
followed previously in this setting to improve sensitivity of p24
antigen detection [22, 23].
In the sexually transmitted infection clinic, routine parallel
testing was performed with Determine? HIV-1/2 (Inverness
Medical Japan) and Uni-Gold? Recombigen? HIV (Trinity
Biotech). As a part of routine procedures in this clinic, persons
with negative or discordant HIV antibody rapid test results and
a high risk score on a validated acute HIV risk score algorithm
were referred for individual testing with a Roche Monitor HIV
RNA PCR assay (Roche Molecular Systems) . After in-
formed consent was obtained, specimens were obtained by
the ultrasensitive p24 antigen assay, which was performed in the
Inthe HIV testing andcounseling center,routineserialtesting
was performed first with the Determine? HIV-1/2 assay, and
then, if positive, with the Uni-Gold? Recombigen? HIV assay
following national protocol. For discordant results, SD Bioline
HIV 1/2 3.0, (Standard Diagnostics) was the arbiter. As part of
study protocol, the Combo RT was added for study participants.
All study participants whose results were negative or discordant
(positive for Determine? HIV-1/2 antibody assay, negative for
Uni-Gold? Recombigen? and Bioline HIV 1/2 3.0 assays) were
tested individually with the Roche Monitor HIV RNA PCR and
ultrasensitive p24 antigen assay.
Acute HIV Point-of-Care Diagnostic
d JID 2012:205 (15 February)
In both settings, participants were classified as HIV negative if
they had negative or discordant rapid antibody test results and
undetectable HIV RNA. They were classified as having acute
HIV infection if they had negative or discordant rapid antibody
test results and detectable HIV RNA and were classified as
having established HIV infection if they had 2 positive rapid
antibody test results.
Among individuals without established HIV infection, the sen-
sitivity and specificity of the Combo RT antigen (Ag) and the
ultrasensitive p24 antigen assay were calculated using the defi-
nition of acute HIV infection mentioned earlier. Additionally,
among those without established HIV infection, the sensitivity
and specificity of the Combo antibody alone, and in combina-
tion with Combo RT Ag, were assessed for acute HIV infection
using the foregoing definition. Among those without acute HIV
infection, the performance of Combo RT antibody (Ab) was
assessed for established HIV infection using the definition of
established HIV infection mentioned earlier. We used exact
methods to calculate 95% confidence intervals (CIs). The j
coefficient for agreement between Combo RT Ab and
Determine? HIV-1/2 results was calculated. Analyses were
conducted using SAS software, version 9.2 (SAS Institute)
and Stata software, version 10 (StataCorp).
The study was approvedbytheInstitutional Review Boardat the
University of North Carolina at Chapel Hill and by the National
Health Sciences Research Committee, which is the local ethics
committee in Malawi.
Characteristics of Study Population
Overall, 1009 participants had complete HIV status information
and a Combo RT Ag result, including 195 in the sexually
transmitted infection clinic and 814 in the HIV testing and
counseling center (Table 1). An additional 5 persons in the
sexually transmitted infection clinic and 29 in the HIV testing
and counseling center were excluded because their true HIV
status could not be determined or because they lacked a Combo
RT Ag result.
Most participants were male (sexually transmitted infection
clinic, 65%, HIV testing and counseling center, 52%). The mean
age was 28 years (standard deviation, 7) in the sexually trans-
HIV testing and counseling center. In the sexually transmitted
infection clinic, 7 persons (4%) had acute HIV infection and
188 (96%) were HIV negative. Inthe HIV testing and counseling
center, 1 person (0.1%) had acute HIV infection, 163 (20%) had
established HIV infection, and 650 (80%) were HIV negative.
Performance of the Combo RT Antigen Component
In the field, using whole blood, results of the Combo RT Ag
were negative in all 8 persons with acute HIV infection
(sensitivity, 0.000; 95% CI, .000–.369) (Table 2). HIV RNA
values for the 8 persons with acute HIV infection were
$750 000 copies/mL in 6 and 45 000 and 359 000 copies/mL
in the other 2. After completion of enrollment, we examined
stored plasma from 6 of the persons with acute HIV infection;
all 6 of the stored plasma specimens were negative with the
Combo RT Ag.
Among the 838uninfected persons across both testing sites, we
observed 14 false-positive Combo RT Ag results, for an overall
0.957 (95% CI, .918–.982) for the sexually transmitted infection
clinic, and a specificity of 644/650 or 0.991 (95% CI, .980–.997)
for the HIV testing and counseling center. None of the HIV-
uninfected persons with false-positive Combo RT Ag results had
discordant rapid test results.
With the observed sensitivity and specificity, the positive
predictive value (PPV) of the Combo RT Ag would be 0%,
regardless of acute HIV prevalence. However, given that the
sensitivity estimate is based on a small number of specimens, we
assessed the upper range of plausible PPVs of the Combo RT Ag
using the upper 95% confidence limits of the overall sensitivity
(0.369), the overall specificity (0.991), and the specificity in the
HIV testing and counseling center (0.997). With the overall
sensitivity and specificity values, in a setting with a relatively
Table 1. Population Characteristics
Participants, No. (%)
(n 5 195)
(n 5 814)
(n 5 1009)
Male125 (0.65) 417 (0.52)542 (0.55)
68 (0.35)378 (0.48)446 (0.45)
18–2468 (0.35) 235 (0.29)303 (0.30)
25–34 90 (0.46)367 (0.45)457 (0.46)
29 (0.15) 135 (0.17)164 (0.16)
7 (0.04) 70 (0.09)77 (0.08)
188 (0.96)650 (0.80) 838 (0.83)
0 (0.00) 163 (0.20)163 (0.16)
Acute infection7 (0.04) 1 (0.001)8 (0.01)
Abbreviations: HIV, human immunodeficiency virus; HTC, HIV testing and
counseling; STI, sexually transmitted infection.
aInformation on sex was missing for 2 participants in the STI clinic and 19 in
the HTC center.
bInformation on age was missing for 1 participant in the STI clinic and 7 in the
cIndividuals in the STI clinic with established HIV infection were excluded.
d JID 2012:205 (15 February)
d Rosenberg et al
high acute HIV prevalence (1%), the PPV would be 29.3%, and
with the HIV testing and counseling center specificity, the PPV
would be 55.4%.
Detection of p24 Antigen Using the Ultrasensitive p24 Antigen
Of 8 persons with acute HIV infection, 7 had sufficient specimen
quantity for ultrasensitive p24 antigen assessment. Five of
7 persons with acute HIV infection had detectable p24 antigen
with this assay (sensitivity, 0.714; 95% CI, .290–.963). The HIV
RNA concentrations for the 2 persons with negative ultrasensi-
tive p24 antigen assays were 45 000 and $750 000 copies/mL.
antigen assay (806/806; specificity, 1.000; 95% CI, .995–1.000).
Performance of Antibody and Combined Antigen and Antibody
Components of Combo RT for Acute HIV Infection
Although the Combo RT Ag results were negative in all 8 per-
sons with acute HIV infection, 2 persons without established
HIV infection had positive Combo RT Ab results (sensitiv-
ity, 0.250; 95% CI, .032–.651) (Table 2). However, 6 of 836
persons without HIV infection had false-positive antibody re-
sults (specificity, 0.993; 95% CI, .984–.997), and 18 of 836
persons had false-positive antibody or antigen results (specific-
ity, 0.979; 95% CI, .966–.987). In a setting with a 1% acute HIV
prevalence, the PPV for acute HIV detection among persons
without established HIV infection would be 26.1% for the an-
tibody strip alone and 10.5% when the antigen and antibody
strips were considered together.
Performance of Combo RT HIV Antibody Component for
Established HIV Infection
Of the 813 participants from the HIV testing and counseling
center without acute HIV infection, 2 HIV-negative persons had
participants evaluated with Combo RT Ab, 163 had established
HIV infection using the HIV testing and counseling center
algorithm. The antibody portion of the Combo RT identified
162 of these persons (sensitivity, 0.994; 95% CI, .966–1.000).
Among 648 persons without HIV infection, we observed 5 false-
positive Combo RT Ab results, yielding a specificity of 0.992
(95% CI, .982–.997) (Table 2). In this population with an esta-
portion was 0.970 (95% CI, .932–.990).
We also compared the Combo RT Ab to the standard De-
termine? HIV-1/2 Ab test used routinely in the HIV testing and
counseling center. Among 171 persons with positive De-
termine? HIV-1/2 Ab results, 165 had positive and 6 had neg-
ative Combo RT Ab results. Among 640 persons with negative
Determine? HIV-1/2 Ab results, 638 had negative and 2 had
positive Combo RT Ab results. The j coefficient for overall
agreement was 0.970 (95% CI, .950–.991).
Identification of persons with acute HIV infection represents
a significant challenge, owing to the absence of antibodies in the
earliest stages, limitations of standard rapid tests to detect p24 or
Table 2. Sensitivity and Specificity of the Combo RT and Ultrasensitive p24 Antigen Assays
AssayTP FNTNFP Sensitivity (95% CI) Specificity (95% CI)
Acute HV infection
Combo RT Ag
Overall08 824 140.000 (.000–.369) 0.983 (.972–.991)
HTC center01 6446 0.000 (.000–.975)0.991 (.980–.997)
07 1808 0.000 (.000–.410) 0.957 (.918–.982)
Combo RT Aba
52 8060 0.714 (.290–.963) 1.000 (.995–1.000)
Combo RT Ag or Aba
26 8306 0.250 (.032–.651)0.993 (.984–.997)
Overall26 818 180.250 (.032–.651)0.979 (.966–.987)
Established HIV infection
Combo RT Aba,c
HTC center 1621 6435 0.994 (.966–1.000)0.992 (.982–.997)
Abbreviations: Ab, antibody; Ag, antigen; CI, confidence interval; FN, false-negative; FP, false-positive; HIV, human immunodeficiency virus; HTC, HIV testing and
counseling; STI, sexually transmitted infection; TN, true-negative; TP, true-positive.
aCombo RT Ab results were missing for 2 participants.
bUltrasensitive p24 antigen assay results were missing for 3 participants in the STI clinic and 30 in the HTC center.
cThe participant with acute HIV infection was excluded.
Acute HIV Point-of-Care Diagnostic
d JID 2012:205 (15 February)
in HIV transmission, an acute HIV test meeting the ‘‘ASSURED’’
criteria (Affordable, Sensitive, Specific, User-friendly, Robust and
rapid, Equipment-free, and Deliverable)  for routine world-
wide use is urgently needed. The Combo RT has been marketed
as such a test, because it is relatively inexpensive and can be
administered at the point of care. However, in this field evaluation
of the Combo RT, the sensitivity and specificity of the p24 antigen
component of the test were inadequate for widespread use for
detecting acute HIV infection. The Combo RT Ag failed to detect
the 8 cases of acute HIV infection and falsely classified 14 other
with the antibody component.
Developing a point-of-care test with adequate sensitivity and
specificity for acute HIV detection is extremely challenging.
Given the brief window of acute HIV infection, the acute HIV
prevalencein a population isvery low at any given point in time,
even among relatively high-risk groups. Consequently, a test
must have exceptional performance characteristics to be useful,
especially without additional confirmatory testing. The Combo
RT was designed to provide a marginal reduction in the HIV
window period. However, even assuming that the sensitivity of
the Combo RT for acute HIV infection was 50%, in a popula-
tion with a high acute HIV prevalence (1%), more than half
of those identified with acute HIV infection would be false
positives, unless the specificity was greater than 0.995. Thus,
to detect even 50% of cases with reasonable certainty, a near-
perfect specificity is required, a characteristic not achieved in
our field evaluation.
Evaluation of tests capable of identifying persons with acute
HIV infection is also complicated by the low prevalence of
acute HIV infection and the brief window period. During de-
velopment, the Combo RT was evaluated using stored speci-
mens to ensure a reasonable number of cases of acute HIV
infection could be assessed . However, evaluation in a lab-
oratory with serum, plasma, or spiked whole blood is not the
same as a field evaluation, especially for a test designed to be
used at the point of care. Field evaluations on finger-stick blood
are crucial for assessing real-world performance characteristics,
even though they are expensive, time consuming, and chal-
lenging to conduct. Although the performance characteristics
of the Combo RT Ag were insufficient for use in this clinical
setting, field evaluation in other settings may be warranted to
assess whether the test performs better.
The Combo RT has been previously evaluated with stored
serum or plasma specimens. In a comparison with the laboratory-
based ARCHITECT HIV Ag/Ab Combo (Abbott Laboratories)
Combo RT detected fewer acute infections in stored serum or
plasma (17% vs 80%) and fewer recent infections (59% vs 89%)
on a panel of specimens . In a clinic-based performance
assessment of 5 rapid tests, neither the antigen nor the antibody
component of Combo RT detected the 2 recent infections using
finger-stick blood .
The reasonsforlowsensitivityof the ComboRTAg inourfield
evaluation may be related to the time course and detection of p24
antigenemia. The heat-dissociation and signal-amplification steps
used in the ultrasensitive p24 antigen assay substantially improve
the detection of the p24 antigen, which is often in a bound form
[20, 22, 23]. The ultrasensitive p24 antigen assay provides the
most sensitive antigen detection method available. The limit of
detection of the ultrasensitive p24 antigen assay can be as low as
172 fg/mL , ?100 times lower than the limit of detection
reported for the Combo RT antigen component (12.5–25 pg/mL)
. However, the heat-dissociation and signal-amplification
steps are not feasible for a rapid-test strip. In some cases, HIV
RNA may be detectable through PCR, but p24 antigen levels may
be below detection limits, even with ultrasensitive p24 antigen
assays. In our study, among the 7 persons with acute HIV and
ultrasensitive p24 antigen assay results, 2 were negative for p24
antigen, suggesting very low levels of antigenemia. Of those with
p24 antigen present in the ultrasensitive assay, the concentration
of free, unbound p24 antigen may have been below the detection
limits of the Combo RT Ag, other non–heat-dissociated p24
assays, or both.
Alternatively, performance could have been due to reduced
in this study, clade C is the predominant Malawian strain and
accounts for nearly all HIV infections [28–30]. The package
insert and published data to date provide little information
about the performance of the antigen component of the
Combo RT by clade [18, 31, 32]. Among 22 stored plasma
samples from persons with clade C acute HIV infection,
results for the antigen portion of the Combo RT were negative
in all 22, although 6 had positive results with the antibody
portion (J Moodley, unpublished data).
One potential concern regarding the Combo RT performance
both the Determine? HIV-1/2 antibody test and the Combo RT
use the same platform, the false-positive antigen results with the
Combo RT cannot be explained by an association with false-
positive Determine? HIV-1/2 antibody results in the reference
standard. None of the false-positive Combo RT Ag results were
observed in persons with discordant rapid test results (ie, pos-
itive for Determine? HIV-1/2 antibody and negative for Uni-
Gold? Recombigen? HIV antibody).
In contrast to the antigen component, the antibody portion
of the Combo RT performed well in detecting established HIV
infection, consistent with the performance of the Determine?
HIV-1/2 antibody test [3, 4]. The strong correspondence of
the Combo RT antibody component and the Determine?
HIV-1/2 rapid test suggests that the Combo RT was deployed
properly in the field.
d JID 2012:205 (15 February)
d Rosenberg et al
The antibody component of Combo RT also identified more
persons with acute HIV infection than the antigen component.
Acute HIV infection was not detected by the antigen component
25% of participants. The sensitivity of the antibody component
for acute HIV detection is compatible with results from similar
settings, where discordant antibody results are strong predictors
of acute HIV infection [19, 33]. In a setting with a 1% acute HIV
prevalence, in a population of persons without established HIV
infection, a positive result on either of the 2 Combo RT strips is
indicative of acute HIV infection 10% of the time, but a positive
result on the antibody strip alone is indicative of acute HIV
infection 26% of the time. This observation underscores the
excellentperformance characteristics ofthe antibodycomponent
of the Combo RT, and the poor, even potentially detrimental,
characteristics of the antigen component.
Closing the seronegative window after HIV infection is im-
portant. Persons with acute HIV infection contribute dispro-
to diagnose. A point-of care acute HIV diagnostic that meets all
ASSURED criteria is urgently needed. Assessment of any pro-
spective test for acute HIVinfection must start with evaluation of
samples. However, at some point, assessment must include field
evaluation to offer clinicians information on how to interpret
results in clinical settings. This field evaluation suggests that
a false-positive result than a true case of acute HIV infection,
a finding that must be considered if this test is used in practice.
the teams at the Lighthouse Trust HIV testing and counseling center,
Kamuzu Central Hospital Sexually Transmitted Infection Clinic, and UNC
Project laboratory. Specifically, we would like to thank Clement Mapanje,
Happiness Kanyamula Malino, and Hilex Kamzati at the sexually trans-
mitted infection clinic. We would like to thank Shadreck Puruma at the
HIV testing and counseling center. We would also like to thank Inverness
(now Alere) for a limited supply of test kits.
Financial support. This study was supported by grants from the US
National Institutes of Health [DHHS/NIH/NIAID 5 T32 AI 07001-34 and
NIAID R01 AI083059]. Study sponsors played no role in study design,
collection or analysis of data, interpretation of results, writing of the
manuscript, or decision to submit for publication. Inverness (now Alere)
provided 69 (6.8%) of the Determine? HIV-1/2 Ag/Ab Combo rapid tests
used in this study.
Potential conflicts of interest. S. A. F. has consulted for Abbott
Molecular, Roche Molecular, and Gen-Probe. All other authors report no
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
We would like to acknowledge the hard work of
1. Parekh BS, Kalou MB, Alemnji G, Ou CY, Gershy-Damet GM,
Nkengasong JN. Scaling up HIV rapid testing in developing countries:
comprehensive approach for implementing quality assurance. Am J
Clin Pathol 2010; 134:573–84.
2. Yao K, Wafula W, Bile EC, et al. Ensuring the quality of HIV rapid
testing in resource-poor countries using a systematic approach to
training. Am J Clin Pathol 2010; 134:568–72.
3. van den Berk GE, Frissen PH, Regez RM, Rietra PJ. Evaluation of the
rapid immunoassay determine HIV 1/2 for detection of antibodies to
human immunodeficiency virus types 1 and 2. J Clin Microbiol 2003;
4. Piwowar-Manning EM, Tustin NB, Sikateyo P, et al. Validation of
rapid HIV antibody tests in 5 African countries. J Int Assoc Physicians
AIDS Care 2010; 9:170–2.
5. Stekler JD, Swenson PD, Coombs RW, et al. HIV testing in a high-
incidence population: is antibody testing alone good enough? Clin
Infect Dis 2009; 49:444–53.
6. Patel P, Mackellar D, Simmons P, et al. Detecting acute human immu-
nucleic acid amplification testing for human immunodeficiency virus
RNA, 2006–2008. Arch Intern Med 2010; 170:66–74.
7. Zetola NM, Pilcher CD. Diagnosis and management of acute HIV
infection. Infect Dis Clin North Am 2007; 21:19–48.
8. Morrison CS, Demers K, Kwok C, et al. Plasma and cervical viral loads
among Ugandan and Zimbabwean women during acute and early
HIV-1 infection. AIDS 2010; 24:573–82.
9. Pilcher CD, Tien HC, Eron JJ Jr, et al. Brief but efficient: acute HIV
infection and the sexual transmission of HIV. J Infect Dis 2004; 189:
10. Fiebig EW, Wright DJ, Rawal BD, et al. Dynamics of HIV viremia
and antibody seroconversion in plasma donors: implications for
diagnosis and staging of primary HIV infection. AIDS 2003; 17:
11. Pilcher CD, Shugars DC, Fiscus SA, et al. HIV in body fluids during
primary HIV infection: implications for pathogenesis, treatment and
public health. AIDS 2001; 15:837–45.
Basic, clinical, and public health Perspectives. N Engl J Med 2011; 364:
13. Bell SK, Little SJ, Rosenberg ES. Clinical management of acute
HIV infection: best practice remains unknown. J Infect Dis 2010;
14. Moir S, Buckner CM, Ho J, et al. B cells in early and chronic HIV
infection: evidence for preservation of immune function associated
with early initiation of antiretroviral therapy. Blood 2010; 116:5571–9.
15. Eshleman SH, Khaki L, Laeyendecker O, et al. Detection of individuals
with acute HIV-1 infection using the ARCHITECT HIV Ag/Ab Combo
assay. J Acquir Immune Defic Syndr 2009; 52:121–4.
16. Branson BM. The future of HIV testing. J Acquir Immune Defic Syndr
2010; 55(Suppl 2):S102–5.
17. Pilcher CD, Christopoulos KA, Golden M. Public health rationale for
nucleic acid or p24 antigen tests for HIV. J Infect Dis 2010; 201:10.
18. Determine HIV-1/2 Ag/Ab combo test [package insert]. Princeton, NJ:
Inverness Medical Innovations, 2009.
19. Powers KA, Miller WC, Pilcher CD, et al. Improved detection of acute
HIV-1 infection in sub-Saharan Africa: development of a risk score
algorithm. AIDS 2007; 21:2237–42.
20. Schupbach J, Flepp M, Pontelli D, Tomasik Z, Luthy R, Boni J. Heat-
mediated immune complex dissociation and enzyme-linked immuno-
sorbent assay signal amplification render p24 antigen detection in plasma
as sensitive as HIV-1 RNA detection by polymerase chain reaction. AIDS
21. Schupbach J. Measurement of HIV-1 p24 antigen by signal-
amplification-boosted ELISA of heat-denatured plasma is a simple
and inexpensive alternative to tests for viral RNA. AIDS Rev 2002;
22. Fiscus SA, Pilcher CD, Miller WC, et al. Rapid, real-time detection
of acute HIV infection in patients in Africa. J Infect Dis 2007; 195:
Acute HIV Point-of-Care Diagnostic
d JID 2012:205 (15 February)
23. Mwapasa V, Cachafeiro A, Makuta Y, et al. Using a simplified human Download full-text
immunodeficiency virus type 1 p24 antigen assay to diagnose pediatric
HIV-infection in Malawi. J Clin Virol 2010; 49:299–302.
24. Peeling RW, Mabey D. Point-of-care tests for diagnosing infections in
the developing world. Clin Microbiol Infect 2010; 16:1062–9.
25. Pandori MW, Louie B, Pilcher C, et al. Assessing the sensitivities of
laboratory-based and point-of-care HIV antigen-antibody combina-
tion tests using a panel of specimens from recently and acutely infected
individuals. HIV Diagnostics Conference, Orlando, FL, 2010; http://
Accessed 20 December 2011.
26. Pavie J, Rachline A, Loze B, et al. Sensitivity of five rapid HIV tests
on oral fluid or finger-stick whole blood: a real-time comparison in
a healthcare setting. PLoS One 2010; 5:e11581.
27. Pascual A, Cachafeiro A, Funk ML, Fiscus SA. Comparison of an assay
using signal amplification of the heat-dissociated p24 antigen with
the Roche Monitor human immunodeficiency virus RNA assay. J Clin
Microbiol 2002; 40:2472–5.
28. Petch LA, Hoffman IF, Jere CS, et al. Genotypic analysis of the protease
and reverse transcriptase of HIV type 1 subtype C isolates from anti-
retroviral drug-naive adults in Malawi. AIDS Res Hum Retroviruses
29. Kwiek JJ, Russell ES, Dang KK, et al. The molecular epidemiology of
in Malawian mother-infant pairs. AIDS 2008; 22:863–71.
30. Hosseinipour MC, van Oosterhout JJ, Weigel R, et al. The public health
approach to identify antiretroviral therapy failure: high-level nucleo-
side reverse transcriptase inhibitor resistance among Malawians failing
first-line antiretroviral therapy. AIDS 2009; 23:1127–34.
31. Keren T, Guidasci T, Rivetz B, Fish F. Performance evaluation of the
determine HIV 1/2 Ag/Ab combo, a novel HIV 4th-generation rapid
test [abstract WEPDC205]. In: 5th IAS Conference on HIV Patho-
genesis and Treatment. Cape Town, 2009.
32. Keren T, Rusu I, Dwir O, Pessler-Cohen D, Sharon Y, Fish F. A new
HIV 4th generation rapid test: determine HIV Ag/Ab Combo [abstract
THPE0052]. In: 17th International AIDS Conference. Mexico, 2008.
33. Bassett IV, Chetty S, Giddy J, et al. Screening for acute HIV infection in
South Africa: finding acute and chronic disease. HIV Med 2011; 12:
d JID 2012:205 (15 February)
d Rosenberg et al