Reactive Rapid Test Research Articles

Hepatitis C genotype distribution and homology among geographically disparate injecting drug users in Afghanistan

Hepatitis C virus (HCV) prevalence is high among injecting drug users in Afghanistan, but transmission dynamics are poorly understood. Samples from HCV-infected injecting drug users were sequenced to determine circulating genotypes and potential transmission linkages. Serum samples were obtained from injecting drug user participants in Hirat, Jalalabad, and Mazar-i-Sharif between 2006 and 2008 with reactive anti-HCV rapid tests. Specimens with detected HCV viremia were amplified and underwent sequence analysis. Of 113 samples evaluated, 25 samples (35.2%) were only typeable in NS5B, nine samples (12.7%) were only typeable in CE1, and 37 samples (52.1%) were genotyped in both regions. Of those with typeable HCV, all were Afghan males with a mean age of 31.1 (standard deviation [SD] ± 8.0) years and mean duration of injecting of 3.9 (SD ± 4.3) years. Most reported residence outside Afghanistan in the last decade (90.1%) and prior incarceration (76.8%). HCV genotypes detected were: 1a, (35.2%, n = 25), 3a (62.0%, n = 44), and 1b (2.8%, n = 2). Cluster formation was detected in NS5B and CE1 and were generally from within the same city. All participants within clusters reported being a refugee in Iran compared to 93.5% of those outside clusters. Only 22.2% (4/11) of those within clusters had been refugees in Pakistan and these four individuals had also been refugees in Iran. Predominance of genotype 3a and the association between HCV viremia and having been a refugee in Iran potentially reflects migration between Afghanistan and Iran among IDUs from Mazar-i-Sharif and Hirat and carry implications for harm reduction programs for this migratory population.

Missed Opportunities: Refusal to Confirm Reactive Rapid HIV Tests in the Emergency Department

BackgroundHIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care.MethodologyIn the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol.Principal FindingsThirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage.ConclusionsThese findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations.Trial RegistrationClinicalTrials.gov NCT00502944; NCT01258582.

The Prevalence and Correlates of Receiving Confirmatory HIV Test Results Among Newly Diagnosed HIV-Positive Individuals at a Community-Based Testing Center

This study examined the prevalence and correlates of completing the HIV testing process-specifically receiving a confirmatory HIV test and returning for the results-in a sample of newly diagnosed HIV-positive individuals at an HIV testing center in New York City. Of the 213 individuals who received a reactive rapid HIV test result, 82% received a confirmatory HIV test. Of the 236 individuals who received a positive result on a rapid or traditional HIV test that was validated by a positive confirmatory HIV test, 65% returned for the confirmatory test results. Multivariate analyses revealed that being a non-U.S. citizen, homeless/living in transitional housing, being uninsured, and testing off-site were significantly associated with completing the HIV testing process. The findings indicate the need to explore strategies that address obstacles to receiving confirmatory HIV testing and returning for the results, in addition to the feasibility of a rapid confirmatory HIV test.

Development of New, Broadly Reactive, Rapid IgG and IgM Lateral Flow Assays for Diagnosis of Scrub Typhus

We evaluated the diagnostic accuracy of two broadly reactive rapid immunochromatographic tests (ICTs) for detection of IgM and IgG against Orientia tsutsugamushi by using archived acute-phase serum samples from 102 patients with laboratory-confirmed scrub typhus, and from 62 archived serum samples from patients with other causes of fever as a negative control. These ICTs were constructed by using a mixture of recombinant proteins: 1) C1, a chimeric protein containing epitopes of the 56-kD antigen from Karp and TA763 strains; 2) Ktr56; and 3) Gmr56. Sensitivities of the ICTs for detection of IgM and IgG were 90.2% (95% confidence interval [CI] = 84.4-96.0%) and 86.3% (95% CI = 80.9-93.8%), respectively. Specificities were 85.5% (95% CI = 73.9-92.2%) and 96.8% (95% CI = 90.3-100%), respectively. Both assays were more sensitive and specific than the standard immune immunofluorescence assay for the early diagnosis of scrub typhus.

Use of a rapid HIV testing algorithm to improve linkage to care

Background Awaiting definitive diagnosis before scheduling healthcare visits complicates HIV screening and referral. Clients screened by rapid tests as initially reactive often fail to return to receive definitive test results, are not linked to care and enter care late or not at all. Objectives To evaluate statewide, (1) the accuracy of a single-visit, two test HIV rapid testing algorithm (RTA) and (2) its effect on referral to care for positive clients. Study design A two-test RTA was implemented at 24 sites in New Jersey beginning in December 2008. All clients with a reactive rapid HIV test were offered a second rapid HIV test, and RTA results were compared with Western blot (WB). Referral to care occurred based upon two sequential positive rapid tests. Results The RTA program has screened 51,413 individuals obtaining 426 reactive rapid test results; 394 (92.5%) were reactive by a second rapid test, 32 (7.5%) had a negative second rapid test. Twenty-eight individuals refused WB testing. Of 369 RTA-positive individuals who have WB results, 368 (99.5%) were confirmed positive. Of RTA-positive clients, 290 (73.6%), including 25 (6.6%) who refused Western blot, were immediately referred for care including one individual with a false-positive RTA. Conclusions The RTA reduced false positive results by 6.2% and agreed with WB results 99.5% of the time. Improved referral to care compared to traditional rapid HIV screening occurs when immediate referral is based on RTA verification of a preliminary positive rapid test. WB confirmation is not essential for effective screening and contributes to difficulties linking individuals to care.

Another look at Emergency Department HIV screening in practice: no need to revise expectations

BackgroundA recent study reported a lower than expected specificity and positive predictive value of the rapid oral HIV test in the setting of routine emergency department (ED) screening. These results appeared inconsistent with the findings in another urban Emergency Department during the same time period.ObjectiveTo compare the specificity and positive predictive vale (PPV) of an oral rapid HIV test used in an ED screening program in Washington DC with that performed in the USHER clinical trial.DesignPeriod cross-sectional analysis of rapid oral HIV testing conducted in an ongoing HIV screening program emergency department patients.SettingThe George Washington University Emergency Department (Washington DC) from 7 February to 1 October 2007.Patients1,560 adults seen in the ED for non-HIV-related presenting complaints, who participated in the HIV screening program.InterventionRapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered Western blot testing for confirmation.MeasurementsSpecificity and positive predictive value for the program were determined. Findings were compared to those found in the USHER trial.ResultsOf 1,560 patients screened for HIV, 13 [0.8%, 95% CI 0.38% to 1.28%] had a reactive HIV screening test, and all were confirmed to be positive by Western Blot. The specificity was 100% (95% CI 99.6%-100%).LimitationSince non-reactive tests were not confirmed, the test sensitivity cannot be determined.ConclusionReview of our data conflict with findings from the USHER study surrounding false positive OraQuick HIV screening. Our data suggest that rapid HIV screening protocols implemented in EDs outside of the clinical trial paradigm perform effectively without an excess of false positive results. Compared with other screening tests, HIV rapid screening should remain an essential component of ED practice.

HIV Testing in a High‐Incidence Population: Is Antibody Testing Alone Good Enough?

The Centers for Disease Control and Prevention recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing. However, antibody tests have longer "window periods" after HIV acquisition than do nucleic acid amplification tests (NAATs). Public Health-Seattle & King County offered HIV antibody testing to men who have sex with men (MSM) using the OraQuick Advance Rapid HIV-1/2 Antibody Test (OraQuick; OraSure Technologies) on oral fluid or finger-stick blood specimens or using a first- or second-generation enzyme immunoassay. The enzyme immunoassay was also used to confirm reactive rapid test results and to screen specimens from OraQuick-negative MSM prior to pooling for HIV NAAT. Serum specimens obtained from subsets of HIV-infected persons were retrospectively evaluated by use of other HIV tests, including a fourth-generation antigen-antibody combination assay. From September 2003 through June 2008, a total of 328 (2.3%) of 14,005 specimens were HIV antibody positive, and 36 (0.3%) of 13,677 antibody-negative specimens were NAAT positive (indicating acute HIV infection). Among 6811 specimens obtained from MSM who were initially screened by rapid testing, OraQuick detected only 153 (91%) of 169 antibody-positive MSM and 80% of the 192 HIV-infected MSM detected by the HIV NAAT program. HIV was detected in serum samples obtained from 15 of 16 MSM with acute HIV infection that were retrospectively tested using the antigen-antibody combination assay. OraQuick may be less sensitive than enzyme immunoassays during early HIV infection. NAAT should be integrated into HIV testing programs that serve populations that undergo frequent testing and that have high rates of HIV acquisition, particularly if rapid HIV antibody testing is employed. Antigen-antibody combination assays may be a reasonably sensitive alternative to HIV NAAT.

Evaluation of Oral Fluid Enzyme Immunoassay for Confirmation of a Positive Rapid Human Immunodeficiency Virus Test Result

The CDC recommends that a reactive rapid human immunodeficiency virus (HIV) test be confirmed with an approved supplemental test; the performance of an intermediate enzyme immunoassay (EIA) is optional. In support of this recommendation, it was found that of 1,431 reactive rapid HIV test results, 2 (0.1%) had false-negative oral fluid Western blot results and both had false-negative EIA results.

The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm

BackgroundConcerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF) HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT) (two positive RDTs alone for HIV diagnosis) used in voluntary counselling and testing (VCT) sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives.Methodology/Principal Findings2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2® and UniGold HIV® rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm® HIV confirmation test (OIC-HIV). Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2). 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3–6.7) when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9–99.9%) with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used.ConclusionsThe WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV confirmation test is practical and effective in field contexts. We propose that all double-positive HIV RDT samples should undergo further testing to confirm HIV seropositivity until the accuracy of the RDT testing algorithm has been established at programme level.

Challenges in rolling out rapid HIV testing in Australia

In a recent issue of Sexual Health, Chen and Estcourt suggest that rapid HIV testing should be encouraged in Australia, referring to the positive experiences of rapid testing in the USA and UK. In the USA, where there have been low levels of HIV testing among at-risk populations, the introduction of rapid HIV testing has had undeniably impressive effects in increasing testing rates. Consumer experiences of rapid testing also tend to be very positive. However, the attractiveness and benefits of rapid HIV testing may vary depending on the context in which it is implemented. The Australian Federation of AIDS Organisations is currently undertaking a review of rapid HIV testing, drawing on the experience of clinicians, researchers, and community organisations. The review process has identified particular challenges that will need to be addressed if rapid testing is to become more available in Australia. In Australia, there are already high levels of HIV testing among the group most at risk of HIV infection – gay and other homosexually-active men. Surveys of gay men across Australia show that over 80% have ever been tested for HIV, between 40% and 55% have been recently tested (within the past 6 months), and that these levels of testing are relatively stable over time. Given that HIV testing appears to be well established among Australian gay men, it is unlikely (in our opinion) that rapid testing would generate a significant increase in testing rates among this group. Rapid testing might however be useful in: a) maintaining high testing rates; b) encouraging testing uptake among untested men; and c) increasing the frequency of testing among those men most at risk of HIV infection e.g. men who engage in unprotected anal intercourse with casual partners, sexually adventurous men and HIV-negative men with HIVpositive partners. The appeal of rapid testing (quick results, less invasive collection methods, alternative testing locations) may help sustain high testing rates and overcome barriers to firsttime testing or more regular testing. There are, however, some serious challenges in making rapid HIV testing more available in Australia. Currently, there are no rapid HIV tests approved for routine screening in Australia. A few rapid tests are approved for limited use, for example, in emergency situations or assessing occupational exposures. For a rapid test to be approved for routine screening in Australia, it is expected that the test’s performance should be of an equivalent or improved level to that of existing assays. The quality of HIV tests currently used for routine screening in Australia is extremely high. ‘Fourth generation’ combined antigen/antibody assays introduced in 2002 have reduced the window period for detecting early infections and have demonstrated the ability to identify acute infections that would have been missed by previous generations of tests. Rapid assays currently used overseas cannot match these performance levels, so for rapid tests to be approved for wider use in Australia different benefits would have to be suggested or proven e.g. the engagement of previously untested consumers or significant improvements in the consumer experience of testing. There are also challenges in adapting preand post-test discussions to handle the rapid testing process and in deciding how to describe reactive rapid test results to consumers. The advantage of standard testing (in which consumers typically wait for up to a week for their results) is that a confirmatory Western blot can be conducted for reactive results before the consumers return to the test site. While rapid testing would undeniably be attractive to the majority of Australian consumers who would return HIV-negative results, for the minority who would receive reactive results there is likely to be a period of limbo in which they have a ‘preliminary positive’ status requiring confirmation. Overall, while we agree with Chen and Estcourt that rapid HIV testing can generate useful benefits, we believe that its introduction in Australia is not necessarily straightforward. It may be more prudent to run a trial of rapid HIV testing in order to identify the most effective ways to implement this testing technology in Australia, to gauge the responses of consumers and to provide evidence of rapid HIV testing’s public health impact for assessment by regulatory authorities.

Implementation of Rapid HIV Testing Programs in Community and Outreach Settings: Perspectives from Staff at Eight Community-Based Organizations in Seven U.S. Cities

The goals of this research were to evaluate perceptions of staff about the effectiveness of methods used by eight community-based organizations (CBOs) to implement human immunodeficiency virus (HIV) counseling and rapid testing in community and outreach settings in seven U.S. cities, and to identify operational challenges. A survey was administered to CBO staff to determine their perceptions about the effectiveness of methods used to select testing venues, promote their testing programs, recruit people for testing, provide test results, and link HIV-positive people to health care. Using a Likert scale, respondents rated the effectiveness of methods, their agreement with statements about using mobile testing units (MTUs) and rapid HIV test kits, and operational challenges. Most respondents perceived the methods they used for selecting testing venues, and particularly using recommendations from people receiving testing, to be effective. Most respondents also thought their promotional activities were effective. Respondents believed that using MTUs improved their capacity to reach high-risk individuals, but that MTUs were associated with substantial challenges (e.g., costs to purchase and maintain them). Programmatic challenges included training staff to provide counseling and testing, locating and providing confirmatory test results to people with reactive rapid tests, and sustaining testing programs. CBO staff thought the methods used to select venues for HIV testing were effective and that using MTUs increased their ability to provide testing to high-risk individuals. However, using MTUs was expensive and posed logistical difficulties. CBOs planning to implement similar programs should take these findings into consideration and pay particular attention to training needs and program sustainability.

Revising Expectations from Rapid HIV Tests in the Emergency Department

Expanded HIV screening efforts in the United States have increased the use of rapid HIV tests in emergency departments. The reported sensitivity and specificity of rapid HIV tests exceed 99%. To assess whether a reactive rapid oral HIV test result correctly identifies adults with HIV infection in the emergency department. Diagnostic test performance assessment within the framework of a randomized, clinical trial. Brigham and Women's Hospital emergency department (Boston, Massachusetts) from 7 February to 1 October 2007. 849 adults with valid rapid oral HIV test results. Rapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered enzyme-linked immunoassay, Western blot, and plasma HIV-1 RNA testing for confirmation. Specificity and positive likelihood ratio. 39 patients had reactive results (4.6% [95% CI, 3.2% to 6.0%]). On confirmation, 5 patients were HIV-infected (prevalence, 0.6% [CI, 0.1% to 1.1%]) and 26 were non-HIV-infected (8 patients declined confirmation). The estimated rapid test specificity was 96.9% (CI, 95.7% to 98.1%). Sensitivity analyses of the true HIV status of unconfirmed cases and test sensitivity resulted in a positive likelihood ratio of 8 to 32. Western blot alone as a confirmation test provided conclusive HIV status in only 50.0% (CI, 30.8% to 69.2%) of patients at first follow-up. The addition of HIV-1 RNA testing to the confirmation protocol improved this rate to 96.2% (CI, 88.8% to 100.0%). Test sensitivity cannot be assessed because nonreactive OraQuick test results were not confirmed. Although patients with a reactive oral OraQuick HIV screening test in the emergency department had an 8- to 32-fold increased odds of HIV infection compared with the pretest odds, the specificity of the test was lower than anticipated.

Repeat Confirmatory Testing for Persons with Discordant Whole Blood and Oral Fluid Rapid HIV Test Results: Findings from Post Marketing Surveillance

BackgroundReactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB), immunofluorescent assay (IFA) or approved nucleic acid amplification test (NAAT)). When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result), repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results.MethodologyPost-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing.Principal FindingsOf 167,371 rapid tests conducted, 2589 (1.6%) were reactive: of these, 2417 (93%) had positive WB/IFA, 172 (7%) had negative or indeterminate WB/IFA. Of 89/172 (52%) persons with a repeat confirmatory test: 17 (19%) were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81%) were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative) (p<0.001) and having an initial oral fluid WB (vs. serum) (p<0.001). Persons who had male-female sex (vs. male-male sex) were at increased risk for not having a repeat test [adjusted OR 2.6, 95% CI (1.3, 4.9)].ConclusionsThough only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for persons with discordant results. Because of the lower sensitivity of oral fluid WBs, confirmatory testing following a reactive rapid test should be conducted using serum or plasma, when possible.

Differences Between Proof-of-Concept Studies and Effective Implementation

Differences Between Proof-of-Concept Studies and Effective Implementation

Rapid HIV Antibody Testing in the New York State Anonymous HIV Counseling and Testing Program

To assess rapid and conventional HIV test use, client satisfaction, and counselors' comfort. At 61 HIV test sites in New York State, we compared HIV test use during the first 6 months of rapid testing in 2003 with the same time period in 2002. We administered surveys to clients at each site during the first 30 days of rapid testing and to counselors before and after training and after 12 weeks of using rapid tests in the field. Almost all (1249 [96.5%] of 1294) clients surveyed selected rapid over conventional HIV testing. During the evaluation period, 6187 HIV tests were reported, 1667 (36.9%) more than during the same period in 2002. All 5771 (100%) of 5771 clients received their rapid HIV test results compared with 333 (85.8%) of 388 clients (P < 0.0001) who had elected conventional testing. After performing rapid testing for 12 weeks, 32 (80%) of 40 trained counselors reported feeling "very comfortable" delivering reactive rapid test results compared with 14 (35%) of 40 trained counselors (P < 0.001) before training. Rapid testing presents a key opportunity to increase the number of people undergoing HIV testing and the proportion receiving their test results.

Post-marketing surveillance of OraQuick whole blood and oral fluid rapid HIV testing

Post-marketing surveillance was conducted to monitor the performance of the OraQuick Advance rapid HIV-1/2 antibody test (OraQuick) on whole blood and oral fluid. Surveillance of routinely collected data on clients tested with OraQuick in 368 testing sites affiliated with 17 state and city health departments between 11 August 2004 and 30 June 2005. For whole blood and oral fluid, we report the median (range) health department OraQuick specificity and positive predictive value (PPV), and the number of clients with discordant results (e.g. who had a reactive rapid test not confirmed positive by Western blot or indirect immunofluorescence). At one site with lower than expected oral-fluid specificity, we evaluated whether device expiration, manufacturing lot, operator practices, or device-storage or testing-area temperatures were associated with false-positive tests. During the surveillance period, 135 724 whole blood and 26 066 oral fluid rapid tests were conducted. The median health department whole blood OraQuick specificity was 99.98% (range: 99.73-100%) and PPV was 99.24% (range: 66.67-100%); the median oral fluid specificity was 99.89% (range: 99.44-100%) and PPV was 90.00% (range: 50.00-100%). A total of 124 discordant results were reported from 68 (0.05%) whole blood and 56 (0.22%) oral fluid rapid tests. The oral fluid specificity at the site with excess oral fluid false-positive tests was 98.7% (95% confidence interval: 98.18-99.11%). The increase in false-positive tests at that site was not associated with any specific device characteristic, operator procedure or temperature condition. The specificity of OraQuick performed on whole blood and oral fluid during post-marketing surveillance was compatible with the manufacturer's claim within the package insert. However, one site experienced lower than expected oral fluid specificity. Sites that observe that the specificity of OraQuick is lower than the range indicated in the package insert should notify the manufacturer and evaluate quality assurance procedures.

Comparison of point-of-care rapid HIV testing in three clinical venues

Rapid HIV testing with same-visit results should increase the number of individuals who know they are HIV infected. We assessed the acceptability and feasibility of point-of-care rapid testing in three public venues, a sexually transmitted disease clinic, a county jail, and an emergency department. Over 98% of all participants received their results, and 82% of newly identified HIV-positive participants entered care. Point-of-care rapid testing was feasible, acceptable, and may improve entry into care.

Protocols for Confirmation of Reactive Rapid HIV Tests

Protocols for Confirmation of Reactive Rapid HIV Tests