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 ADVANCEH 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 #1 to$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 ADVANCEH with oral fluid declined significantly wit

Risky business: A mixed methods study of decision-making regarding COVID-19 risk at a public university in the United States

IntroductionUntil vaccines became available in late 2020, our ability to prevent the spread of COVID-19 within countries depended largely on voluntary adherence to mitigation measures. However, individual decision-making regarding acceptable COVID-19 risk is complex. To better understand decision-making regarding COVID-19 risk, we conducted a qualitative substudy within a larger Berkeley COVID-19 Safe Campus Initiative (BCSCI) during the summer of 2020, and completed a mixed-methods analysis of factors influencing decision-making.Materials and methodsWe interviewed 20 participants who tested positive for SARS-CoV-2 and 10 who remained negative, and analyzed quantitative survey data from 3,324 BCSCI participants. The BCSCI study enrolled university-affiliated people living in the local area during summer of 2020, collected data on behaviors and attitudes toward COVID-19, and conducted SARS-CoV-2 testing at baseline and endline.ResultsAt baseline, 1362 students (57.5%) and 285 non-students (35.1%) said it had been somewhat or very difficult to comply with COVID-19-related mandates. Most-cited reasons were the need to go out for food/essentials, difficulty of being away from family/friends, and loneliness. Eight interviewees explicitly noted they made decisions partially because of others who may be at high risk. We did not find significant differences between the behaviors of students and non-students.DiscussionDespite prevailing attitudes about irresponsibility of college students during the COVID-19 pandemic, students in our study demonstrated a commitment to making rational choices about risk behavior, not unlike non-students around them. Decision-making was driven by perceived susceptibility to severe disease, need for social interaction, and concern about risk to others. A harm reduction public health approach may be beneficial

Challenges to the performance of current HIV diagnostic assays and the need for centralized specimen archives: a review of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) repository.

Background: New challenges for diagnosis of HIV infection abound, including the impact on key viral and immunological markers of HIV vaccine studies, pre-exposure prophylaxis usage and breakthrough infections, and very early initiation of anti-retroviral treatment. These challenges impact the performance of current diagnostic assays, and require suitable specimens for development and evaluation. In this article we review and describe an archive developed by the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), in order to identify the critical features required to create a centralized specimen archive to support these current and future developments. Review and Findings: We review and describe the CEPHIA repository, a large, consolidated repository comprised of over 31,000 highly-selected plasma samples and other body fluid specimen types, with over 50 purposely designed specimen panels distributed to 19 groups since 2012. The CEPHIA repository provided financial return on investment, supported the standardization of HIV incidence assays, and informed guidance and standards set by the World Health Organization and UNAIDS. Unified data from extensively characterized specimens has allowed this resource to support biomarker discovery, assay optimization, and development of new strategies for estimating duration of HIV infection. Critical features of a high-value repository include 1) extensively-characterized samples, 2) high-quality clinical background data, 3) multiple collaborations facilitating ongoing sample replenishment, and 4) sustained history of high-level specimen utilization. Conclusion: With strong governance and leadership, a large consolidated archive of samples from multiple studies provides investigators and assay developers with easy access to diverse samples designed to address challenges associated with HIV diagnosis, helping to enable improvements to HIV diagnostic assays and ultimately elimination of HIV. Its creation and ongoing utilization should compel funders, institutions and researchers to address and improve upon current approaches to sharing specimens

Sexually transmitted infection screening to prevent adverse birth and newborn outcomes: study protocol for a randomized-controlled hybrid-effectiveness trial

Background Sexually transmitted infections (STIs) during pregnancy are associated with adverse birth outcomes, including preterm birth, low birth weight, perinatal death, and congenital infections such as increased mother-to-child HIV transmission. Prevalence of STIs among pregnant women in South Africa remains high, with most women being asymptomatic for their infection(s). Unfortunately, most STIs remain undetected and untreated due to standard practice syndromic management in accordance with World Health Organization (WHO) guidelines. Although lab-based and point-of-care molecular tests are available, optimal screening strategies during pregnancy, their health impact, and cost-effectiveness are unknown. Methods We will implement a 3-arm (1:1:1) type-1 hybrid effectiveness-implementation randomized-controlled trial (RCT). We will enroll 2500 pregnant women attending their first antenatal care (ANC) visit for their current pregnancy at participating health facilities in Buffalo City Metro District, Eastern Cape Province, South Africa. Participants allocated to arms 1 and 2 (intervention) will receive GeneXpert® point-of-care diagnostic testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, with same-day treatment for detected infection(s). Arm 1 will additionally receive a test-of-cure 3 weeks post-treatment, while Arm 2 will receive a repeat test at 30–34 weeks’ gestation. Those allocated to Arm 3 will receive syndromic management (standard-of-care). The RE-AIM framework will be used to guide collection of implementation indicators to inform potential future scale up. Primary outcome measures include (1) frequency of adverse birth outcomes among study arms, defined by a composite measure of low birth weight and pre-term delivery, and (2) change in STI prevalence between baseline and birth outcome among intervention arms and compared to standard-of-care. Estimates and comparative costs of the different screening strategies relative to standard-of-care and the costs of managing adverse birth outcomes will be calculated. Cost-effectiveness will be assessed per STI and disability-adjusted life year averted. Discussion This trial is the first RCT designed to identify optimal, cost-effective screening strategies that decrease the burden of STIs during pregnancy and reduce adverse birth outcomes. Demonstrating the impact of diagnostic screening and treatment, compared to syndromic management, on birth outcomes will provide critical evidence to inform changes to WHO guidelines for syndromic management of STIs during pregnancy. Trial registration ClinicalTrials.gov NCT04446611 . Registered on 25 June 2020

Performance of Risk-Based Criteria for Targeting Acute HIV Screening in San Francisco

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.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.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.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

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

CAPRISA, 2017.Abstract available in pdf