Using a Multitest Algorithm to Improve the Positive Predictive Value of Rapid HIV Testing and Linkage to HIV Care in Nonclinical HIV Test Sites.

BACKGROUND: Use of a rapid HIV testing algorithm (RTA) in which all tests are conducted within one client appointment could eliminate off-site confirmatory testing and reduce the number of persons not receiving confirmed results. METHODS: An RTA was implemented in 9 sites in Los Angeles and San Francisco; results of testing at these sites were compared with 23 sites conducting rapid HIV testing with off-site confirmation. RTA clients with reactive results on more than 1 rapid test were considered HIV+ and immediately referred for HIV care. The positive predictive values (PPVs) of a single rapid HIV test and the RTA were calculated compared with laboratory-based confirmatory testing. A Poisson risk regression model was used to assess the effect of RTA on the proportion of HIV+ persons linked to HIV care within 90 days of a reactive rapid test. RESULTS: The PPV of the RTA was 100% compared with 86.4% for a single rapid test. The time between testing and receipt of RTA results was on average 8 days shorter than laboratory-based confirmatory testing. For risk groups other than men who had sex with men, the RTA increased the probability of being in care within 90 days compared with standard testing practice. CONCLUSIONS: The RTA increased the PPV of rapid testing to 100%, giving providers, clients, and HIV counselors timely information about a client's HIV-positive serostatus. Use of RTA could reduce loss to follow-up between testing positive and confirmation and increase the proportion of HIV-infected persons receiving HIV care.

Who are the sexual partners of transgender individuals? Differences in demographic characteristics and risk behaviours of San Francisco HIV testing clients with transgender sexual partners compared with overall testers.

UNLABELLED: Background Research to examine the sexual networks of transgender people may be the key to understanding why transwomen are at high risk of contracting HIV. METHODS: Bivariate and multivariate analysis of San Francisco HIV county counselling and testing data from 2010 was conducted to compare demographic factors and risk behaviours of the partners of transgender people (PTG) to HIV testing clients overall. RESULTS: Of the 13754 clients overall, 477 reported having sex with a transgender person in the past 12 months. PTG were significantly more likely to be transgender, Latino, multiracial or 'other', and identify as bisexual. In multivariate analyses, PTG were significantly more likely to have used and injected drugs in the past 12 months; in bivariate analysis, PTG had a significantly higher likelihood of having unprotected vaginal or anal sex. PTG who had engaged in vaginal or anal sex in the past 12 months had an HIV positivity of 0.6% compared with 1.1% for non-PTG. CONCLUSIONS: People who report having transgender sexual partners engage in higher-risk behaviours than other HIV testers yet had a lower HIV positivity. Potential explanations for the discrepancy between higher-risk behaviours and lower HIV positivity for PTG may be engagement in HIV-protective behaviours like regular HIV testing and lower risk seropositioning being the insertive sexual partner. Future studies on the sexual networks of transgender people, and sexual and risk behaviours of PTG may elucidate the HIV risk for both PTG and their transgender partners.

Performance of rapid point-of-care and laboratory tests for acute and established HIV infection in San Francisco.

BACKGROUND: Current laboratory and point-of-care tests for HIV detect different analytes and use different sample types. Some have fast turnaround times (<1 hour). We investigated how HIV test choice could impact case finding by testing programs. METHODS: We analyzed 21,234 consecutive HIV tests with venous blood obtained by San Francisco HIV testing programs from 2003 to 2008. For a subset, oral fluid (n = 6446) or fingerstick blood (n = 8127) samples were also obtained for rapid testing. In all cases, HIV status was determined using an HIV antibody-plus-RNA test algorithm. We assessed how the screening antibody tests performed individually versus the gold standard of the full algorithm. We then evaluated the potential ability of other tests (including new tests) to detect more cases, by re-testing all specimens that had negative/discrepant antibody results on initial screening. FINDINGS: The antibody-RNA algorithm identified 58 acute and 703 established HIV infection cases. 1(st)-generation (Vironostika) and 3(rd)-generation (Genetic Systems) immunoassays had 92 and 96 percent sensitivity, respectively. The Oraquick rapid test had clinical sensitivity of only 86 percent on oral fluid samples, but 92 percent on finger-stick blood. Newer 4(th)-generation, antigen-antibody combo rapid immunoassay (ARCHITECT) detected HIV in 87 percent of all the acute cases that had been missed by one of the previous screening assays. A point-of-care 4(th) generation antigen-antibody combo rapid test (Determine) detected about 54 percent of such acute cases. CONCLUSIONS: Our study suggests that some rapid antibody blood tests will give similar case detection to laboratory antibody tests, but that oral fluid testing greatly reduces ability to detect HIV. New 4(th)-generation combo tests can detect the majority of acute infections detectable by HIV RNA but with rapid results. Using these tests as a primary screening assay in high-risk HIV testing programs could reduce or eliminate the need for HIV RNA testing.

Using social networks to reach Black MSM for HIV testing and linkage to care.

Black men who have sex with men (MSM) are disproportionately affected by HIV infection. Black MSM in San Francisco may have higher rates of unrecognized HIV infections. Increased HIV testing among Black MSM may reduce the numbers of unrecognized infections, inform more men of their status and thus reduce the potential for ongoing transmissions. Social network HIV testing programs have focused on asking HIV-positive and/or high-risk negative men to recruit their social or sexual contacts. We used a network approach to deliver HIV testing to Black MSM in San Francisco and collected risk assessment data. Participants were asked to recruit any of their social contacts who were also Black MSM. Recruitment by risk level and HIV status was heterogeneous. HIV infection among this population is associated with older age, having a high school education or higher and currently being homeless. Fully 23% of HIV positive Black MSM are unaware of their infection. Only a third of unrecognized infections were recruited by a known HIV-positive participant. Linkage to care was a challenge and underscores the need for comprehensive systems and support to link Black MSM to care and treatment.

Performance of risk-based criteria for targeting acute HIV screening in San Francisco.

BACKGROUND: Federal guidelines now recommend supplemental HIV RNA testing for persons at high risk for acute HIV infection. However, many rapid HIV testing sites do not include HIV RNA or p24 antigen testing due to concerns about cost, the need for results follow-up, and the impact of expanded venipuncture on clinic flow. We developed criteria to identify patients in a municipal STD clinic in San Francisco who are asymptomatic but may still be likely to have acute infection. METHODS: Data were from patients tested with serial HIV antibody and HIV RNA tests to identify acute HIV infection. BED-CEIA results were used to classify non-acute cases as recent or longstanding. Demographics and self-reported risk behaviors were collected at time of testing. Multivariate models were developed and preliminarily evaluated using predictors associated with recent infection in bivariate analyses as a proxy for acute HIV infection. Multivariate models demonstrating ≥70% sensitivity for recent infection while testing ≤60% of patients in this development dataset were then validated by determining their performance in identifying acute infections. RESULTS: From 2004-2007, 137 of 12,622 testers had recent and 36 had acute infections. A model limiting acute HIV screening to MSM plus any one of a series of other predictors resulted in a sensitivity of 83.3% and only 47.6% of patients requiring testing. A single-factor model testing only patients reporting any receptive anal intercourse resulted in 88.9% sensitivity with only 55.2% of patients requiring testing. CONCLUSIONS: In similar high risk HIV testing sites, acute screening using "supplemental" HIV p24 antigen or RNA tests can be rationally targeted to testers who report particular HIV risk behaviors. By improving the efficiency of acute HIV testing, such criteria could facilitate expanded acute case identification.

Testing and linkage to care outcomes for a clinician-initiated rapid HIV testing program in an urban emergency department.

The urban emergency department is an important site for the detection of HIV infection. Current research has focused on strategies to increase HIV testing in the emergency department. As more emergency department HIV cases are identified, there need to be well-defined systems for linkage to care. We conducted a retrospective study of rapid HIV testing in an urban public emergency department and level I trauma center from June 1, 2008, to March 31, 2010. The objectives of this study were to evaluate the increase in the number of tests and new HIV diagnoses resulting from the addition of targeted testing to clinician-initiated diagnostic testing, describe the demographic and clinical characteristics of patients with newly diagnosed HIV infection, and assess the effectiveness of an HIV clinic based linkage to care team. Of 96,711 emergency department visits, there were 5340 (5.5%) rapid HIV tests performed, representing 4827 (91.3%) unique testers, of whom 62.4% were male and 60.8% were from racial/ethnic minority groups. After the change in testing strategy, the median number of tests per month increased from 114 to 273 (p=0.004), and the median number of new diagnoses per month increased from 1.5 to 4 (p=0.01). From all tests conducted, there were 65 new diagnoses of HIV infection (1.2%, 95% confidence interval [CI] 0.9%, 1.5%). The linkage team connected over 90% of newly diagnosed and out-of-care HIV-infected patients to care. In summary, the addition of targeted testing to diagnostic testing increased new HIV case identification, and an HIV clinic-based team was effective at linkage to care.

False positive rate of rapid oral fluid HIV tests increases as kits near expiration date.

BACKGROUND: Because a recent cluster of false positive results on the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test occurred in San Francisco on test kits close to their expiration date, we decided to assess the relationship between time to expiration and rate of false positive results from tests used with oral fluid. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed results of 20,904 tests with either an initial HIV-negative result (n = 20,828) or a preliminary positive result that was then negative on confirmatory tests (n = 76). We computed specificity for kits with time to expiration from < or = 1 to > or = 6 months, with exact binomial confidence intervals, then used logistic regression to estimate the independent association of time to expiration with false positive results, adjusting for site and technician effects. For 1,108 kits used in the last month before expiration, specificity was 98.83% (95% exact binomial confidence interval (CI) 98.00%-99.37%); the upper bound is below the claimed specificity of 99.60%. After adjustment using regression standardization for the effects of site, test lot, and technician factors, adjusted specificity in the last month before expiration was 99.18% (95% bootstrap confidence interval 98.60-99.57%). CONCLUSIONS/SIGNIFICANCE: We found that specificity of the OraQuick ADVANCE with oral fluid declined significantly with < or = 1 month remaining to expiration, leaving little margin for error from other sources.

Assessment of the ability of a fourth-generation immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen to detect both acute and recent HIV infections in a high-risk setting.

An immunoassay (IA) that simultaneously detects both antibody to human immunodeficiency virus (HIV) and HIV p24 antigen (Architect HIV Ag/Ab Combo) was evaluated for its ability to detect HIV infection by using a panel of specimens collected from individuals recently infected with HIV type 1 (HIV-1). This IA was found to be capable of detecting the majority (89%) of infections, including 80% of those considered acute infections based on the presence of HIV RNA and the lack of detectable antibody to HIV. Substantial improvements in detection of recent infections by the Architect HIV Ag/Ab Combo relative to previous generations of IAs as well as the capacity to detect acute infections have important implications for HIV prevention strategies.

Assessment of sensitivity and specificity of first, second, and third generation EIA for the detection of antibodies to HIV-1 in oral fluid.

The performances of three blood-based immunoassays test kits were compared with regard to their ability to detect HIV-1 antibody in oral fluid. It was found that these three kits differ in their ability to detect HIV-1 antibody. Notably, a third generation EIA which has been shown to possess superior sensitivity for antibody detection in plasma appears to possess no sensitivity advantage for detecting HIV-1 antibody in oral fluid.

Simplifying consent for HIV testing is associated with an increase in HIV testing and case detection in highest risk groups, San Francisco January 2003-June 2007.

BACKGROUND: Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis. METHODS: Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH) medical care system were included in the analysis. The monthly HIV testing rate per 1000 had patient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language. RESULTS: By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17-6.60, p<0.001) over the number predicted if the policy change had not occurred (representing a 44% increase). The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3-11.5) to 14.9 (CI, 10.6-19.2, p<0.001), representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change. CONCLUSIONS: The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change.

Prevalence and correlates of unknown HIV infection among patients seeking care in a public hospital emergency department.

OBJECTIVES: Screening for human immunodeficiency virus (HIV) infection in the emergency department (ED) has been proposed as an effective approach to increase early HIV diagnosis. To evaluate the potential for the implementation of routine screening, we determined the prevalence of unknown HIV infection among patients being seen in an urban public hospital ED. METHODS: We conducted a cross-sectional study among patients presenting to the San Francisco General Hospital's ED during March 2007. We reviewed patients' medical records to determine HIV infection status. In patients with unknown or negative HIV-infection status, we tested de-identified remnant blood specimens by HIV-antibody and nucleic-acid assays. We used a sensitive/less sensitive testing algorithm to determine the duration of HIV infection. RESULTS: During the study period, 1,820 patients had blood collected for clinical evaluation. Of those patients, 146 (8.0%) were known to be HIV-infected. Among the remaining 1,674 patients with unknown HIV-infection status, HIV-infection prevalence was 0.9% (15 of 1,674, 95% confidence interval [CI] 0.55, 1.47). In addition, one case of acute HIV infection (HIV-antibody negative, HIV RNA detected) was identified. Patients with unknown HIV infection vs. those who were uninfected were more likely to be homeless (odds ratio [OR] = 3.89, 95% CI 1.32, 11.45, p<0.05) and 18 to 30 years of age (OR=3.15, 95% CI 1.03, 9.61, p<0.05). CONCLUSIONS: In a sample of patients visiting a county ED, the relative prevalence of unknown HIV infection (10%) was modest and less than national estimates (25%). Acutely HIV-infected patients might account for a significant proportion of those with unknown HIV infection in an ED setting.

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

OBJECTIVE: 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. DESIGN: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.