Alere Determine HIV-1 Research Articles

Profile of Interferon-gamma levels in patients infected with <i>mycobacterium tuberculosis</i> and coinfected with human immunodeficiency virus in Yaoundé

Tuberculosis remains a major public health problem globally with HIV/AIDS being the main predisposing factor to Mycobacterium tuberculosis (MTB) infection. Interferon Gamma (IFN- ) is one of the most important cytokines in the host immune response against this mycobacterium. This study aimed to determine the profile of IFN- levels in patients infected with Mycobacterium tuberculosis and co- infected with HIV in Yaoundé. A descriptive cross-sectional study was carried out in the Yaoundé Jamot Hospital and the Yaoundé University Teaching Hospital from August - November 2021. Ninety (90) participants were enrolled (45 pulmonary tuberculosis (PTB) cases and 45 healthy controls). ALERE DETERMINE HIV-1/2 rapid diagnostic test plus HIV AB/AG ELISA HUMAN COMBO was used for HIV screening, and IFN- levels were measured by sandwich ELISA method. Among the 45 cases, 35 were PTB infected only, while 10 (22.2%) were HIV/TB co-infected. IFN- levels were higher in the TB-HIV co-infected group (7.24pg/ml ± 6,9) and the TB mono-infected group (4.11pg/ml ± 3.02) as compared to healthy controls (3.31 ± 2.14). In TB patients, a negative correlation was observed between the IFN- levels and the duration of antituberculosis therapy, indicating the importance of IFN- in accelerating recovery from PTB following treatment. Considering the limited number of cases studied, further studies are needed to demonstrate the value of this cytokine in the management of MTB in Cameroon.

2079. Comparison of Recency Assays to Estimate HIV Incidence in the SIENA (eStimating hIv incidEnce amoNg Agyw) Study in Uganda

Abstract Background HIV-1 recent infection testing algorithms (RITAs) use recency assays to estimate population level HIV incidence rates (IRs), and are currently being employed in PrEP trials to estimate background HIV incidence rates (bHIV-IR). The SIENA study was conducted to determine the HIV incidence rate among young women in and around central and mid-western Uganda, and to assess the suitability of different recency assay platforms for use in determining bHIV-IR in future PrEP trials. Methods Diagnosis of HIV was confirmed by positive results on both the Alere Determine HIV-1/2 and Oraquick HIV-1/2 rapid tests. Positive samples were analyzed for recent infection using the Sedia HIV-1 Limiting Antigen Avidity Enzyme ImmunoAssay (LAg-EIA; Sedia Biosciences, Beaverton, OR) and the Sedia Asante HIV-1 Rapid Recency Assay (Asante; Sedia Biosciences). The Asante assay was performed by electronic reader (Asante-Reader) or visual read (Asante-Visual). VL was determined by COBAS TaqMan HIV-1 Test (LabCorp, Indianapolis, IN). HIV incidence was calculated based on previously determined MDRI and FRRs that were specific for the study population. Results Of 743 women screened, 191 were diagnosed with HIV, of whom 44 (23%) had a viral load of < 75 copies/mL. The 3 recency assays identified between 43 and 57 samples as recent and between 35 and 37 samples when the VL cutoff of < 75 copies/mL was used (Table). When no VL cutoff was used the calculated bHIV-IR was 17.9/100 person-years (PY) for the LAg-EIA, 12.8/100PY for the Asante-Reader and 20.3/100PY for the Asante-Visual. Using the VL cutoff, the calculated bHIV-IR was 11.4/100 PY with the LAg-EIA assay and 10.9/100 PY with the Asante-Reader. No MDRI or FRR for the Asante-Visual with a VL cutoff was available for calculation of the Asante-Visual HIV incidence. Conclusion When the RITA included a VL cutoff of 75 cp/mL, the LAg-EIA and Asante assays classified the number of recent and long-term infections similarly, resulting in comparable bHIV-IR results. Overall, these analyses support the use of these recency assays in the RITA to estimate the bHIV-IR in future PrEP trials. Our results demonstrate extremely high prevalence and incidence of HIV in young women in central and mid-western Uganda, highlighting the need for expanded HIV prevention options in these areas. Disclosures Stephanie Cox, BS, Gilead Sciences: Paid employee|Gilead Sciences: Stocks/Bonds Shelley N. Facente, PhD, MPH, CDC-funded TRACE program: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Sedia Biosciences Corporation: Grant/Research Support Eduard Grebe, PhD, CDC-funded TRACE program: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Sedia Biosciences Corp: Grant/Research Support Ramin Ebrahimi, MS, Gilead Sciences: Paid employee|Gilead Sciences: Stocks/Bonds Christoph C. Carter, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds Christian Callebaut, PhD, Gilead Sciences: Paid employee|Gilead Sciences: Stocks/Bonds Jared Baeten, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Moupali Das, MD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds.

New infections and HIV-1 subtypes among febrile persons and blood donors in Oyo State, Nigeria.

There were approximately 37.9 million persons infected with HIV in 2018 globally, resulting in 770,000 deaths annually. Over 50% of this infection and deaths occur in sub-Saharan Africa, with countries like Nigeria being seriously affected. Nigeria has one of the highest rates of new infections globally. To control HIV infection in Nigeria, there is a need to continually screen high-risk groups for early HIV infection and subtypes using very sensitive methods. In this study, new HIV-1 infection and circulating HIV-1 subtypes among febrile persons and blood donors were determined. Performance characteristics of three commercial EIA kits were also evaluated. In total, 1028 participants were recruited for the study. New HIV-1 infection and subtypes were determined using enzyme immunoassays and molecular techniques, respectively. Sensitivity, specificity, predictive values, and agreements were compared among the EIA kits using PCR-confirmed HIV-positive and negative samples. The overall prevalence of HIV infection in this study was 5.35%. The rate of new HIV infection was significantly different (p < .03674) among 1028 febrile persons (Ibadan: 2.22%; Saki: 1.36%) and blood donors (5.07%) studied. Three subtypes, CRF02_AG, A, and G, were found among those with new HIV infection. Whereas the commercial ELISA kits had very high specificities (94.12%,100%, and 100%) for HIV-1 detection, Alere Determine HIV-1 antibody rapid kit had the lowest sensitivity score (50%). Genetic diversity of HIV-1 strains among infected individuals in Oyo State, Nigeria, is still relatively high. This high level of diversity of HIV-1 strains may impactthe reliability of diagnosis of the virus in Nigeria and other African countries where many of the virus strains co-circulate.

Biotin Interference in Point of Care HIV Immunoassay.

The use of high concentrations of biotin as a dietary supplement to improve hair, skin, and nail quality has increased in the United States over the past few years. High concentrations of biotin have been shown to interfere with some diagnostic assays that use streptavidin–biotin interactions as one of the steps in the assay. The objective of this report is to evaluate potential biotin interference on the analytical and clinical sensitivity of a point of care (POC) antigen–antibody combo HIV-1 assay. We spiked biotin at concentrations ranging from 12.5 to 400 ng/mL into serum and plasma containing HIV-1 subtype B p24 antigen derived from culture supernatant. The p24 antigen was present in the matrices at 30 pg/mL. Fifty microliters of each sample was applied to Alere Determine HIV-1/2 Ag/Ab combo assay strips in duplicate and results were read by eye after 20 to 30 min. Biotin interfered with detection of HIV-1 p24 in serum and plasma. HIV-1 p24 was not detected at 30 pg/mL p24 when biotin was present at 200 ng/mL concentration. Our study demonstrated that elevated levels of biotin in samples may interfere with POC assays. It is important to consider biotin supplements as potential sources of falsely increased or decreased test results, especially in cases wherein supplementation cannot be ruled out.

Prevalence of HIV infection and bacteriologically confirmed tuberculosis among individuals found at bars in Kampala slums, Uganda

Individuals found at bars in slums have several risk factors for HIV and tuberculosis (TB). To determine the prevalence of HIV and TB among individuals found at bars in slums of Kampala, Uganda, we enrolled adults found at bars that provided written informed consent. Individuals with alcohol intoxication were excluded. We performed HIV testing using immunochromatographic antibody tests (Alere Determine HIV-1/2 and Chembio HIV 1/2 STAT-PAK). TB was confirmed using the Xpert MTB/RIF Ultra assay, performed on single spot sputum samples. We enrolled 272 participants from 42 bars in 5 slums. The prevalence of HIV and TB was 11.4% (95% CI 8.1–15.8) and 15 (95% CI 6–39) per 1,000 population respectively. Predictors of HIV were female sex (aOR 5.87, 95% CI 2.05–16.83), current cigarette smoking (aOR 3.23, 95% CI 1.02–10.26), history of TB treatment (aOR 10.19, 95% CI 3.17–32.82) and CAGE scores of 2–3 (aOR 3.90, 95% CI 1.11–13.70) and 4 (aOR 4.77, 95% CI 1.07–21.35). The prevalence of HIV and TB was twice and four times the national averages respectively. These findings highlight the need for concurrent programmatic screening for both HIV and TB among high risk populations in slums.

Field accuracy of HIV rapid diagnostic tests for blood donors screening, Bukavu, Eastern Democratic Republic of the Congo.

Rapid diagnostic tests (RDTs) are widely used for point-of-care. point-of-care diagnosis of HIV infection in resource-limited settings. However, there are no data about their field diagnostic performance in Eastern Democratic Republic of the Congo (DRC), especially in the context of blood banks screening for transfusion safety purpose. Blood specimens were collected from blood donors in Bukavu, Eastern DRC, from May the 1st to June the 30th, 2015, to evaluate the accuracy of Alere Determine HIV-1/2, Trinity Biotech Uni-Gold HIV, and DoubleCheckGold Ultra HIV 1 and 2 compared to the laboratory-based 4th generation ELISA apDia HIV Ag/Ab assay. Sensitivity, specificity, positive and negative predictive values, and related 95% confidence intervals were calculated using MedCalc statistical software version 15.1. Reliability was evaluated using Cohen's Kappa Statistic, K. Among 312 participants who provided blood bags, 96/312 (30.7%) were female and the mean age (SD) was 31.7 years (±8.1 years). Sensitivity for the three tests was 57.1% (95% CI: 18.4-90.1). The specificity was 99.7% (95% CI: 18.4-90.1) for Alere Determine HIV 1/2, 100% (95% CI: 98.8-100.0) for Uni-Gold HIV, and (100% (95% CI: 98.8-100.0) for DoubleCheckGold Ultra HIV 1 and 2. Cohen's Kappa Statistic showed moderate agreement between the 4th generation ELISA apDia HIV Ag/Ab and RDTs Alere Determine HIV 1/2 and Uni-Gold HIV (K = 0.66; 95% CI: 0.55-0.76) but good agreement for DoubleCheckGold Ultra HIV 1 and 2 (K = 0.72; 95% CI: 0.61-0.82). Compared to the laboratory-based ELISA apDia HIV Ag/Ab assay, the currently used 3rd generation HIV RDTs showed poor field accuracy results in a context of blood donors screening. These data support the need for 4th generation Ag-Ab RDTs in transfusion blood qualification.

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OBJECTIVES/SPECIFIC AIMS: High-sensitivity diagnostics for early infant diagnosis (EID) of HIV at the point of care (POC) are not widely available. Lateral flow immunoassays (LFA) can detect HIV-p24, but are not sensitive enough in practice. With improvements, LFA are a compelling platform for POC in EID. We used functionalized magnetic beads and immunocomplex dissociation to improve sensitivity of HIV-p24 LFA. Here, we evaluate the utility for LFA to quantitatively report HIV-p24 concentration and estimate HIV viral load. Using purified p24 protein and virion constructs, we determined the limits of detection for HIV-p24 using LFA rapid tests. Using measurements from HIV-p24 ELISA, laboratory-developed RT-qPCR, droplet digital PCR, and gold standard clinical viral load, we further characterized the relationship between HIV-p24 concentration, HIV genomic RNA, and LFA test line signal. METHODS/STUDY POPULATION: We measured HIV-p24 concentration by ELISA (R&amp;D Systems) and LFA (Alere Determine HIV-1/2 Ab/Ag Combo). An LFA reader instrument was used to image test lines and measure test line signal on the LFA. HIV viral loads were measured using RT-qPCR and droplet digital RT-PCR protocols adapted in our lab. We obtained gold standard viral load measurements using the Roche Cobas TaqMan system at Vanderbilt University Medical Center. Data analysis was performed using Prism 7 and Stata 14. RESULTS/ANTICIPATED RESULTS: LFA test line signal increases in a predictable, dose-dependent manner and correlates with concentration of purified HIV-p24 with a linear range between 50 and 1000 pg/mL (Spearman r=1; p=0.0004). We compared p24 concentration (ELISA). We evaluated the utility of LFA to quantify HIV-p24 from virions suspended in human plasma, which increased the limit of detection for HIV-p24 to 100 pg/mL and shifted the linear range 100–10,000 pg/mL (Spearman r=0.77; p&lt;0.001). To evaluate the relationship between HIV-p24 concentration and concentration of HIV RNA, we employed 3 molecular techniques. The LFA is capable of detecting HIV-p24 concentrations that correspond to a range of viral loads between 653,000 and 1655 copies of viral RNA/mL. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results are very promising, indicating that commercially available LFA can quantitatively measure HIV-p24 concentration to low levels. When coupled with our analysis of the relationship between HIV-p24 concentration and HIV RNA concentration, LFA may be a potential platform allowing us to estimate HIV viral burden at clinically relevant levels. Our next steps will be to evaluate this relationship in primary, clinical specimens in collaboration with the Tennessee Center for AIDS Research. We will incorporate technologies to improve the sensitivity of these LFA and evaluate their performance in field settings in Zambia. Our findings are broadly applicable for use in HIV care and treatment programs and early infant diagnosis programs around the world.

Evaluation of two 4th generation point-of-care assays for the detection of Human Immunodeficiency Virus infection.

BackgroundFourth generation assays detect simultaneously antibodies for HIV and the p24 antigen, identifying HIV infection earlier than previous generation tests. Previous studies have shown that the Alere Determine HIV-1/2 Combo has lower than anticipated performance in detecting antibodies for HIV and the p24 antigen. Furthermore, there are currently very few studies evaluating the performance of Standard Diagnostics BIOLINE HIV Ag/Ab Combo.ObjectiveTo evaluate the performance of the Alere Determine HIV-1/2 Combo and the Standard Diagnostics BIOLINE HIV Ag/Ab Combo in a panel of frozen serum samples.Study designThe testing panel included 133 previously frozen serum specimens from the UCLA Clinical Microbiology & Immunoserology laboratory. Reference testing included testing for HIV antibodies by a 3rd generation enzyme immunoassay followed by HIV RNA detection. Antibody negative and RNA positive sera were also tested by a laboratory 4th generation HIV Ab/Ag enzyme immunoassay.ResultsReference testing yielded 97 positives for HIV infection and 36 negative samples. Sensitivity of the Alere test was 95% (88–98%), while the SD Bioline sensitivity was 91% (83–96%). Both assays showed 100% (90–100%) specificity. No indeterminate or invalid results were recorded. Among 13 samples with acute infection (HIV RNA positive, HIV antibody negative), 12 were found positive by the first assay and 8 by the second. The antigen component of the Alere assay detected 10 acute samples, while the SD Bioline assay detected only one.ConclusionsBoth rapid assays showed very good overall performance in detecting HIV infection in frozen serum samples, but further improvements are required to improve the performance in acute infection.

Prevalence and risk factors associated with sexually transmitted infections (STIs) among women of reproductive age in Swaziland

BackgroundSexually transmitted infections (STIs) remain an important public health problem with approximately half a billion new cases annually among persons aged 15–49 years. Epidemiological data on STIs among women of reproductive age in Swaziland are limited. The availability of epidemiological data on STIs and associated risk factors in this population is essential for the development of successful prevention, diagnosis and management strategies in the country. The study aimed to determine the prevalence and risk factors associated with STIs.MethodsA total of 655 women aged 15–49 years were systematically enrolled from five health facilities using a cross-sectional study design. Cervical specimen were tested using GeneXpert CT/NG Assays for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), GeneXpertTV Assay for Trichomonas vaginalis (TV), and GeneXpert HPV Assays for hr-HPV. Blood samples were tested using Alere Determine HIV-1/2Ag/Ab Combo and Trinity Biotech Uni-Gold Recombigen HIV test for confirmation for HIV, and Rapid Plasma Reagin and TPHA test for confirmation for Treponema pallidum (syphilis). Genital warts were assessed prior to specimen collection. Survey weighted analyses were done to estimate the population burden of STIs.ResultsThe four most common curable STIs: CT, NG, TV, Treponema pallidum (syphilis), as well as genital warts were considered in this study. The overall weighted prevalence of any of these five STIs was 19.4% (95% CI: 14.9–24.8), corresponding to 72 990 women with STIs in Swaziland. The estimated prevalences were 7.0% (95% CI: 4.1–11.2) for CT, 6.0% (95% CI: 3.8–8.8) for NG, 8.4% (95% CI: 5.4–12.8) for TV, 1.4% (95% CI: 1.1–10.2) for syphilis and 2.0% (95% CI: 1.0–11.4) for genital warts. The overall weighted HIV prevalence was 42.7% (95%CI: 35.7–46.2). Among hr-HPV positive women, 18.8% (95% CI: 13.1–26.3) had one STI, while 6.3% (95% CI: 3.3–11.7) had multiple STIs. Risk factors associated with STIs were being employed (OR = 2.2, 95% CI: 1.0–4.7), self-employed (OR = 2.8, 95% CI: 1.5–5.5) and being hr-HPV positive (OR = 2.0, 95% CI: 1.3–3.1). Age (0.9, 95% CI: 0.8–0.9), being married (OR = 0.4, 95% CI: 0.3–0.7) and not using condoms with regular partners (OR = 0.5, 95% CI: 0.3–0.9) were inversely associated with STIs.ConclusionSTIs are highly prevalent among women of reproductive age in Swaziland. Thus, a comprehensive STIs screening, surveillance and treatment programme would be justified and could potentially lower the burden of STIs in the country.

388 Implementation of an Emergency Department Syphilis and HIV Point-of-Care Screening Process During an Outbreak of Syphilis in Detroit, MI in Collaboration With the Infectious Disease Department and the Centers for Disease Control and Prevention

The number of primary and secondary syphilis cases in Detroit, Michigan increased from 73 in 2010 to 199 to 2013. Cases were predominantly in young African American men with who have sex with men and with had a high rate of HIV co-infection. The infectious disease (ID) department at Henry Ford Hospital (HFH), in collaboration with the Centers for Disease Control and Prevention (CDC) determined the emergency department (ED) would be the optimal setting to implement a screening program. Young men in Detroit are typically non-health care seeking; however, EDs are venues they do frequent when they access the health care system. We hypothesized that the implementation of an ED screening model would detect an increased number of syphilis and HIV cases than were seen with standard care. Point-of-care (POC) testing would allow presumptive treatment of active syphilis cases in the emergency department, whereas traditional testing would not typically result and allow for care within a typical ED visit time frame. Syphilis and HIV screening was offered to men aged 18-34 years seen in the HFH ED with an Emergency Severity Index (ESI) of 2-5. Dedicated, non-ED staff employed 2 rapid finger-stick POC tests: the Alere Determine HIV-1/2 Ag/ab Combo test (Determine) and the Syphilis Heath Check (SHC) treponemal tests. Participants also underwent venipuncture for standard lab-based testing for HIV and syphilis. Screening took place from 7:30am to 5pm, Monday through Friday. Patients were first approached by screeners, typically before the initial clinician contact and were offered screening. Confirmatory lab-based testing using the Biorad 4th generation HIV test, RPR, and TPPA tests were drawn in conjunction with ED nursing staff during their routine bloodwork. ED clinicians were notified of positive SHC POC testing and patients were treated presumptively in the ED. From 6/10/2015 to 3/11/2016, 871 patients were enrolled. Active syphilis (RPR + TPPA +) was identified in 6 (0.7%) participants, and newly diagnosed HIV in 7 (0.8%). There was one case of syphilis-HIV coinfection, and the combined prevalence was 1.4%. Three patients were treated in the ED for syphilis based on their POC testing results without treatment complications. The implementation of an ED syphilis and HIV POC screening program is a feasible method to detect new cases of disease. The screening process can be incorporated into ED patient flow and provide clinicians with immediate test results to determine the need for treatment. POC HIV and syphilis testing are particularly important to ED providers, who may not otherwise receive important test results for their patients before they leave the emergency department.

Diagnosing acute HIV infection at point of care: a retrospective analysis of the sensitivity and specificity of a fourth-generation point-of-care test for detection of HIV core protein p24

ObjectivesDetection of acute HIV infection is vital in preventing onward transmission. HIV point-of-care testing (POCT) has improved uptake of HIV testing but has been limited to third-generation assays, which only...

Transmitted HIV-1 Drug resistance and the Role of Herpes Simplex Virus -2 Coinfection among Fishermen along the Shores of Lake Victoria, Kisumu, Kenya

Introduction: Herpes simplex virus type 2 (HSV-2) infection has been associated with a 3-fold risk of HIV-1 acquisition. The prevalence of HIV-1 and HSV-2 in the fishing communities along the shores of Lake Victoria in Kisumu have been reported to be high. This may contribute to the growing HIV epidemic in Kenya including the spread of transmitted drug resistance (TDR). We report data on the association of HSV2/HIV-1 co-infection and TDR in this antiretroviral (ARV)-naïve population. Methods: Blood samples were obtained from 249 consenting fishermen from 5 beaches and a detailed sociodemographic questionnaire was administered. Blood samples were analyzed for HIV-1/HSV2 co-infection. The HSV-2 serology was performed using Kalon HSV type 2 enzyme-linked immunosorbent assay (ELISA). The HIV-1 counselling and serology were carried out according to local standards of practice in Kenya, using two parallel rapid assays (Alere Determine HIV-1/2 and Trinity Biotech Uni- Gold), with a third ELISA-Vironostika HIV Uni-Form II Ag/Ab for resolving discrepancies. All HIV positive samples were tested for TDR using an in house HIV-1 pol-RT genotyping protocol. Results: Of the 249 recruited fishermen (mean age 35.1 years), 134 (53.8%) were positive for HSV-2, 59 (23.7%) were HIV positive while 48 (19.3%) were HIV/HSV-2 coinfected. Twenty-three of 59 (38.9%) HIV positive men had TDR, with the majority (19/23, 82.6%) in HIV/HSV-2 coinfected fishermen. Among the 48 HIV/HSV-2 co-infected fishermen, 9 had nucleoside reverse-transcriptase inhibitor (NRTI) resistance mutations with NRTI- associated mutations [NAMS], M184V (77.8%) and K65R (11.1%) being the highest. Nineteen (19) fishermen had Non-NRTI (NNRTIs) mutations including; four (21.1%) each of K103N, Y181C and G190A. Three (15.7%) V179T, two V901V and single A98G and Y188L mutations. Among the 11 fishermen who had HIV-1 mono-infection, four (36.4%) had drug resistant mutations. One fisherman had NRTI resistance mutation M184V. In addition, three men (3/4) had NNRTI resistance; K103N, G190A and Y181C mutations each. In the regression model, HIV/HSV-2 co-infection was independently associated with TDR [OR 4.1 (95% CI 1.4 to 11.9)]. Conclusion: The level of TDR to NNRTIs in these ARV-naive fishermen was significantly high especially among those coinfected with HSV-2. HSV-2 infection may increase the risk of TDR in this population.

Comparison of the New Alere HIV Combo with Alere Determine HIV-1/2 Ag/Ab Combo in Acute Primo and Established HIV Infections

Background: Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies but not p24 antigen. Individuals with an acute or early primary HIV infection have generally high viral loads, but do not produce antibodies yet. The first 4th generation rapid test – Alere Determine HIV-1/2 Combo test, disappointedly, gave rarely positive p24-antigen results in acute or early infections. To improve the sensitivity, a new test was developed: Alere HIV Combo test. Methods and Findings: A pilot study should elucidate the performance of the new Alere HIV Combo assay in comparison with Alere Determine HIV-1/2 Combo, and with the reference method. Samples of HIV-1 and HIV-2 infections of patients, who had not been under antiretroviral treatment before, were tested with both the new Alere HIV Combo and the Alere Determine HIV-1/2 Combo. Results were compared with Western blot and HIV viral loads from the reference laboratory. Fifteen samples were from patients with established HIV-1 infections, and two were of HIV-2; six samples were from acute or early primary HIV-1 infections. Fifteen samples were of negative HIV status. Alere Determine HIV-1/2 Combo gave correct results in established infections, where antibodies are produced, whereas in primary infections only HIV-1 of Clade B reacted weakly at the p24-antigen site. The new Alere HIV Combo assay reacted very well with all the positive samples of all clades, also in acute or early primary infections. Conclusions: The new Alere HIV Combo rapid test performs well in detecting anti- HIV antibodies as well as p24-antigen.

Point-of-Care Diagnostics for Acute HIV Infection: An Important Public Health Priority

To the Editor—We appreciate the correspondence in this issue of the Journal by Jones et al and Laperche et al evaluating the performance of the Alere Determine HIV-1/2 Ag/Ab Combo test (Combo point-of-care test [POCT]) for the detection of antibodies for established human immunodeficiency virus (HIV) infection and p24 antigen for acute HIV infection (AHI) [1, 2]. We believe that the earliest stages of HIV infection, including AHI, are critical for both individual health and HIV prevention. During AHI, establishment of latency currently renders HIV infection incurable. Persons with AHI also have high viral loads, making them highly contagious for a brief period. AHI therefore represents an important time for intervention [3]. Identification of subjects with AHI is critical, yet challenging. Since persons are antibody-negative during AHI, HIV rapid tests, which detect HIV antibodies, cannot detect AHI. AHI can be detected only with diagnostics capable of identifying HIV RNA, DNA or p24 antigen. To date, most of these diagnostics have been laboratory-based. In a recent issue of the Journal, we evaluated the Combo POCT, a test designed to concomitantly detect HIV antibodies and p24 antigen in separate reading frames at the point of care [4]. Our study was conducted among persons attending a sexually transmitted infection clinic and an HIV testing and counseling center in Lilongwe, Malawi. We found that the antibody portion of the test had excellent sensitivity and specificity for detecting established HIV infection. However, the antigen portion of the test had zero sensitivity and inadequate specificity for detecting AHI. The antigen portion of the test was unable to identify any of the 8 persons with true AHI, and it falsely classified 6 HIV-uninfected persons as having AHI. Such incorrect results could cause considerable mental anguish, confusion, and cost. Jones et al report similar findings among high-risk persons in the United Kingdom [1]. The antibody portion of the Combo POCT had excellent sensitivity and specificity, but the antigen portion of the test had poor sensitivity and specificity. It did not identify the 2 persons with AHI, and it incorrectly classified 2 HIV-uninfected and 1 antibody-positive person as having AHI. They also noted several invalid tests and implementation challenges owing to a narrow reading interval. Laperche et al assess the sensitivity of the Combo POCT at different p24 concentrations and among different clades in archived plasma and stored supernatants [2]. Even in these laboratory settings, the Combo POCT was unable to detect p24 consistently, especially with non-B subtypes. Although laboratory testing can be an important early step for gauging when a test may or may not perform adequately, it simply cannot replace field testing, which is required to determine ultimate utility. This is especially important for a test like the Combo POCT, which is designed to be used at the point of care on finger-stick whole blood. Laperche et al note the difficulty of field testing for AHI. However, we and others have demonstrated the feasibility of this approach. We have reported elsewhere that AHI can be detected routinely in the sexually transmitted infection setting where we conducted our analysis [5], allowing us to conduct ongoing studies related to this stage of HIV disease [6–7]. Although the performance of the antigen portion of the Combo POCT has been disappointing, the goal of identifying persons during AHI is important [8]. Investigators and industry should work together toward designing sensitive and specific diagnostics that can detect AHI at the point of care. These diagnostics must then be field tested before clinical use, regardless of the degree of difficulty involved.