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Background: Indeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and its sociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda., Methods: 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15-49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results., Results: The prevalence of HIV serologically indeterminate results was 4.9%. Indeterminate results were less likely among women than men (adjPR 0.76, 95% CI 0.71,0.81), in unmarried participants than married participants (adjPR 0.92, 95% CI 0.85,99), and in individuals with primary (adjPR 0.90, 95% CI 0.80,1.02), secondary (adjPR 0.83, 95% CI 0.73,0.96) and post-secondary (adjPR 0.75, 95% CI 0.60,0.94) education, relative to no education. The proportions of persons with indeterminate results progressing to HIV positive, negative or indeterminate results in subsequent visits was 5%, 71% and 24%, respectively., Conclusion: HIV serologically indeterminate results were associated with gender and marital status. HIV surveillance programs should develop a protocol for reporting individuals with mixed or persistently indeterminate HIV results on multiple follow-up visits. Most indeterminate results became HIV-negative over time, but follow-up is still needed to detect positive serologies., Competing Interests: The authors have declared that no competing interests exist.

Background: HIV screening (i.e. antigen/antibody) tests are followed by a supplemental (i.e. antibody-only) if the screen is positive. Discrepant results can result from two scenarios: a false-positive screening test or acute HIV infection. These scenarios can be distinguished by a molecular HIV test, but due to contamination concerns, our laboratory recently implemented a policy requiring a second specimen dedicated for molecular HIV testing. Our objective was to (1) characterize the effect of this policy on the time-to-diagnosis for patients with discrepant screening and supplemental test results, and (2) explore "strength of positivity" as an interim predictor of screening test accuracy while awaiting confirmatory test results., Methods: Data from our laboratory information system, electronic health record, and instrument logs were used to collate data for all HIV testing performed at Barnes-Jewish Hospital (BJH) between January 1, 2014 and October 18, 2017., Results: Requiring a dedicated specimen for molecular testing significantly increased the time-to-diagnosis for patients with discrepant screening and supplemental HIV tests (p = 0.0084). This policy also contributed to loss-to-followup, with 0/35 discrepant cases lost-to-followup prior to policy implementation compared to 2/10 after implementation. However, by optimizing the signal-to-cutoff (S/CO) ratio of the screening test, we were able to more accurately distinguish false-positives from acute-HIV prior to molecular testing (sensitivity of 100%, specificity of 89%)., Conclusions: We propose utilizing quantitative fourth-generation assay results (S/CO) ratios as a predictor of infection true positivity in situations where the screening assay is reactive but the supplemental test is negative and confirmatory molecular results are not immediately available., Competing Interests: The authors have declared that no competing interests exist.

Background: An individual is considered HIV positive when a confirmatory HIV-1/HIV-2 differentiation test returns positive following an initial reactive antigen/antibody combination screen. Falsely reactive HIV screens have been reported in patients with various concomitant infectious and autoimmune conditions. Falsely positive confirmatory HIV differentiation assays are seen less frequently, but have been observed in cases of pregnancy, pulmonary embolism, and malaria., Case Presentation: A healthy 27 year-old man was referred after a reactive ADVIA Centaur® HIV Ag/Ab screen and positive Bio-Rad Geenius™ HIV 1/2 Confirmatory assay, suggesting HIV-1 infection. The patient's HIV viral load was undetectable prior to initiation of antiretroviral therapy, and remained undetectable on subsequent testing after initiation of antiretroviral therapy. Both Centaur® and Geenius™ tests were repeated and returned reactive. As this patient was believed to be at low risk of acquiring HIV infection, samples were additionally run on Genscreen™ HIV-1 Ag assay and Fujirebio Inno-LIA™ HIV-1/2 score, with both returning non-reactive. For confirmation, the patient's proviral HIV DNA testing was negative, confirming the initial results as being falsely positive. The patient disclosed that he had been using a variety of anabolic steroids before and during the time of HIV testing., Discussion and Conclusions: The erroneous diagnosis of HIV can result in decreased quality of life and adverse effects of antiretroviral therapy if initiated, hence the importance of interpreting the results of HIV testing in the context of an individual patient. This reports suggests a potential association between the use of anabolic steroids and falsely-reactive HIV testing.

Objective: This is the first large-scale assessment of the implementation of HIV Rapid Test Quality Improvement Initiative in South Africa., Methods: We used a quasi-experimental one group post-test only design. The intervention implemented starting April 2014 comprised health-care worker training on quality assurance (QA) of HIV rapid testing and enrolment of the facilities in proficiency testing (PT), targeting 2,077 healthcare facilities in 32 high HIV burden districts. Following the intervention, two consecutive rounds of site assessments were undertaken. The first, conducted after a median of 7.5 months following the training, included 1,915 facilities that participated in the QA training, while the second, conducted after a median of one-year following the first-round assessment included 517 (27.0%) of the 1,915 facilities. In both assessments, the Stepwise-Process-for-Improving-the-quality-of-HIV-Rapid-Testing (SPI-RT) checklist was used to score facilities' performance in 7 domains: training, physical facility, safety, pre-testing, testing, post-testing and external quality assessment. Facilities' level of readiness for national certification was assessed., Result: Between 2016 and 2017, there were four PT cycles. PT participation increased from 32.4% (620/1,915) in 2016 to 91.5% (1,753/1,915) in 2017. In each PT cycle, PT results were returned by 76%-87% of facilities and a satisfactory result (>80%) was achieved by ≥95% of facilities. In the SPI-RT assessment, in round-one, 22.3% of facilities were close to or eligible for national certification-this significantly increased to 38.8% in round-two (P-value<0.001). The median SPI-RT score for the domains HIV pre-testing (83.3%) and post-testing (72.2%) remained the same between the two rounds. The median score for the testing domain increased by 5.6% (to 77.8%)., Conclusion: Facilities performance on the domains that are critical for accuracy of diagnosis (i.e. pre-testing, testing and post-testing) remained largely unchanged. This study provided several recommendations to improve QA implementation in South Africa, including the need to improve routine use of internal quality control for corrective actions., Competing Interests: The authors have declared that no competing interests exist.

Severe malaria is an uncommon diagnosis in the United States. However, awareness of signs, symptoms, and treatment options is imperative in order to promptly initiate optimal therapy. False positive human immunodeficiency virus (HIV) results are rare in the setting of acute malaria infection and with the introduction of newer fourth-generation immunoassays. The Centers for Disease Control algorithms assist in confirming true HIV infection (Branson et al. 2014)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next-generation assays. Three-hundred-member panels of 20 serially diluted well-characterized antibody-negative HIV isolates for which the researchers were blind to the results (blind panels) were distributed to manufacturers and end-user labs to assess the relative analytic sensitivity of currently approved and preapproved clinical HIV fourth-generation Ag/Ab combo or p24 Ag-alone immunoassays for the detection of diverse subtypes. The limits of detection (LODs) of virus were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blind panel. On the basis of the proportion of positive results on 300 observations, all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half-log LODs, illustrating the similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo assays performed poorly. The similar performance of the different commercially available fourth-generation assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next-generation preclinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while rapid fourth-generation assays performed poorly for p24 Ag detection., (Copyright © 2018 American Society for Microbiology.)

Introduction: HIV testing is an invaluable entry point to prevention, care and treatment services for people living with HIV and AIDS. Poor adherence to recommended protocols and guidelines reduces the performance of rapid diagnostic tests, leading to misdiagnosis and poor estimation of HIV seroprevalence. This study seeks to evaluate the adherence of primary healthcare facilities in Cameroon to recommended HIV counselling and testing (HCT) procedures and the impact this may have on the reliability of HIV test results., Methods and Analysis: This will be an analytical cross-sectional study involving primary healthcare facilities from all the 10 regions of Cameroon, selected by a multistaged random sampling of primary care facilities in each region. The study will last for 9 months. A structured questionnaire will be used to collect general information concerning the health facility, laboratory and other departments involved in the HCT process. The investigators will directly observe at least 10 HIV testing processes in each facility and fill out the checklist accordingly., Ethics and Dissemination: Clearance has been obtained from the National Ethical Committee to carry out the study. Informed consent will be sought from the patients to observe the HIV testing process. The final study will be published in a peer-reviewed journal and the findings presented to health policy-makers and the general public., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: In South Africa where the prevalence of HIV infection is very high, 4th generation HIV antibody/p24 antigen combo immunoassays are the tests of choice for laboratory based screening. Testing is usually performed in clinical pathology laboratories on automated analysers. To investigate the cause of false positive results on 4th generation HIV testing platforms in public sector laboratories, the performance of two automated platforms was compared in a clinical pathology setting, firstly on routine diagnostic specimens and secondly on known sero-negative samples., Methods: Firstly, 1181 routine diagnostic specimens were sequentially tested on Siemens and Roche automated 4th generation platforms. HIV viral load, western blot and follow up testing were used to determine the true status of inconclusive specimens. Subsequently, known HIV seronegative samples from a single donor were repeatedly tested on both platforms and an analyser was tested for surface contamination with HIV positive serum to identify how suspected specimen contamination could be occurring., Results: Serial testing of diagnostic specimens yielded 163 weakly positive or discordant results. Only 3 of 163 were conclusively shown to indicate true HIV infection. Specimen contamination with HIV antibody was suspected, based on the following evidence: the proportion of positive specimens increased on repeated passage through the analysers; viral loads were low or undetectable and western blots negative or indeterminate on problem specimens; screen negative, 2nd test positive specimens tested positive when reanalysed on the screening assay; follow up specimens (where available) were negative. Similarly, an increasing number of known negative specimens became (repeatedly) sero-positive on serial passage through one of the analysers. Internal and external analyser surfaces were contaminated with HIV serum, evidence that sample splashes occur during testing., Conclusions: Due to the extreme sensitivity of these assays, contamination with minute amounts of HIV antibody can cause a negative sample to test positive. Better contamination control measures are needed on analysers used in clinical pathology environments, especially in regions where HIV sero-prevalence is high.

Background: Client satisfaction serves as a predictor for acceptance of HIV counselling and testing (HCT) services. Therefore, the study of clients' perception and satisfaction may offer insights on how to improve HCT programmes., Aim and Setting: The aim of this study was to assess clients' satisfaction with HCT as well as describe perceived barriers to and facilitators of HIV testing by HCT clients in South Africa., Methods: A cross-sectional survey was conducted through interviews with 498 clients purposefully selected at the end of an HCT visit at 56 HCT sites throughout the country., Results: All the 498 study participants had tested for HIV with 98.8% receiving their results. Most (88.2%) reported testing for HIV before. The vast majority (75.5%) of clients reported that they had decided to be tested for HIV by themselves. High levels of satisfaction with HCT service (89.8%), low levels (27.7%) of difficulty in making the decision to have an HIV test and high levels of perceived confidentiality (94.6%) of the HIV test results were reported in this study. The most cited perceived barrier to HIV testing was lack of awareness about the HCT service (98%), while staff attitudes (37%), confidentiality (29.6%) and privacy (23.6%) were perceived facilitators. In multivariate logistic regression, staff attitude was significantly associated with client satisfaction (p &lt; 0.05)., Conclusion: High levels of client satisfaction with HCT services were observed. Various barriers to and facilitators of - including staff attitude - HCT were identified which can help guide the improvement of HCT services in South Africa.

Little is known about how combining efficacious interventions for human immunodeficiency virus (HIV) prevention could lead to HIV elimination. We used an agent-based simulation model, the HIV calibrated dynamic model, to assess the potential for HIV elimination in South Africa. We examined several scenarios (from continuation of the current status quo to perfect achievement of targets) with differing combinations of male condom use, adult male circumcision, HIV testing, and early antiretroviral therapy (ART). We varied numerous parameters, including the proportion of adult males circumcised, the frequency of condom use during sex acts, acceptance of HIV testing, linkage to health care, criteria for ART initiation, ART viral suppression rates, and loss to follow-up. Maintaining current levels of combination prevention would lead to increasing HIV incidence and prevalence in South Africa, while the perfect combination scenario was projected to eliminate HIV on a 50-year time scale from 2013 to 2063. Perfecting testing and treatment, without changing condom use or circumcision rates, resulted in an 89% reduction in HIV incidence but not elimination. Universal adult male circumcision alone resulted in a 21% incidence reduction within 20 years. Substantial decreases in HIV incidence are possible from sufficient uptake of both primary prevention and ART, but with continuation of the status quo, HIV elimination in South Africa is unlikely within a 50-year time scale., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Testing for human immunodeficiency virus (HIV) is the key first step in HIV treatment and prevention. In 2006, the Centers for Disease Control and Prevention (CDC) recommended annual HIV testing for people at high risk for HIV infection. We evaluated HIV testing among men with high-risk heterosexual (HRH) contact and sexually active men who have sex with men (MSM) before and after the CDC recommendations., Methods: We used data from the National Survey of Family Growth, 2002 and 2006-2010, to assess proportions of HRH respondents and MSM reporting HIV testing in the prior 12 months, compare rates of testing before and after release of the 2006 CDC HIV testing guidelines, and examine demographic variables and receipt of health-care services as correlates of HIV testing., Results: Among MSM, the proportion tested was 37.2% (95% confidence interval [CI] 28.2, 47.2) in 2002, 38.2% (95% CI 25.9, 52.2) in 2006-2008, and 41.7% (95% CI 29.2, 55.3) in 2008-2010; among HRH respondents, the proportion was 23.7% (95% CI 20.5, 27.3) in 2002, 24.5% (95% CI 20.9, 28.7) in 2006-2008, and 23.9% (95% CI 20.2, 28.1) in 2008-2010. HIV testing was more likely among MSM and HRH respondents who received testing or treatment for sexually transmitted disease in the prior 12 months, received a physical examination in the prior 12 months (MSM only), or were incarcerated in the prior 12 months., Conclusions: The rate of annual HIV testing was low for men with sexual risk for HIV infection, and little improvement took place from 2002 to 2006-2010. Interventions aimed at men at risk, especially MSM, in both nonmedical and health-care settings, likely could increase HIV testing.

Novel fourth generation screening and confirmatory human immunodeficiency virus (HIV) assays are now commercially available and incorporated into new diagnostic algorithms. We report two cases involving a total of three patients which highlight the spectrum of false positivity for both the Abbott Architect p24 antigen/antibody assay and the confirmatory Multispot antibody differentiation test. We then discuss the mechanisms for false positivity and the associated clinical conditions or laboratory scenarios that may predispose to inaccurate interpretation.

Objective: This study examined temporal trends in HIV testing among U.S. older adults (50-64 years of age) before and after the release of CDC's routine HIV testing recommendations in 2006., Methods: The sample (n=872,797; 51.4% female) comprised 2003-2010 Behavioral Risk Factor Surveillance System respondents in the oldest categories to which the recommendations apply: 50-54 years (34.5%, n=301,519), 55-59 years (34.1%, n=297,865), and 60-64 years (31.3%, n=273,413). We calculated (1) four-year pooled prevalences of past-year HIV testing before and after 2006, when the recommendations were released; and (2) annual prevalences of HIV testing overall and by age category from 2003-2010. Using weighted, multivariable logistic regression analyses, we examined binary (pre- vs. post-recommendations) and annual changes in testing, controlling for covariates. We stratified the data by recent doctor visits, examined racial/ethnic differences, and tested for linear and quadratic temporal trends., Results: Overall and within age categories, the pooled prevalence of past-year HIV testing decreased following release of the recommendations (p<0.001). The annual prevalence decreased monotonically from 2003 (5.5%) to 2006 (3.6%) (b=-0.16, p<0.001) and then increased immediately after release of the recommendations, but decreased to 3.7% after 2009 (b=0.01, p<0.001). By race/ethnicity, testing increased over time among non-Hispanic black people only. Annual prevalence also increased among respondents with recent doctor visits., Conclusion: CDC's HIV testing recommendations were associated with a reversal in the downward trend in past-year HIV testing among older adults; however, the gains were neither universal nor sustained over time.

Background: Important differences have been demonstrated in laboratory parameters from healthy persons in different geographical regions and populations, mostly driven by a combination of genetic, demographic, nutritional, and environmental factors. Despite this, European and North American derived laboratory reference intervals are used in African countries for patient management, clinical trial eligibility, and toxicity determination; which can result in misclassification of healthy persons as having laboratory abnormalities., Methods: An observational prospective cohort study known as the Kisumu Incidence Cohort Study (KICoS) was conducted to estimate the incidence of HIV seroconversion and identify determinants of successful recruitment and retention in preparation for an HIV vaccine/prevention trial among young adults and adolescents in western Kenya. Laboratory values generated from the KICoS were compared to published region-specific reference intervals and the 2004 NIH DAIDS toxicity tables used for the trial., Results: About 1106 participants were screened for the KICoS between January 2007 and June 2010. Nine hundred and fifty-three participants aged 16 to 34 years, HIV-seronegative, clinically healthy, and non-pregnant were selected for this analysis. Median and 95% reference intervals were calculated for hematological and biochemistry parameters. When compared with both published region-specific reference values and the 2004 NIH DAIDS toxicity table, it was shown that the use of locally established reference intervals would have resulted in fewer participants classified as having abnormal hematological or biochemistry values compared to US derived reference intervals from DAIDS (10% classified as abnormal by local parameters vs. >40% by US DAIDS). Blood urea nitrogen was most often out of range if US based intervals were used: <10% abnormal by local intervals compared to >83% by US based reference intervals., Conclusion: Differences in reference intervals for hematological and biochemical parameters between western and African populations highlight importance of developing local reference intervals for clinical care and trials in Africa.

Introduction: In the field of health, numerous frameworks have emerged that advance understandings of the differential impacts of health policies to produce inclusive and socially just health outcomes. In this paper, we present the development of an important contribution to these efforts - an Intersectionality-Based Policy Analysis (IBPA) Framework., Methods: Developed over the course of two years in consultation with key stakeholders and drawing on best and promising practices of other equity-informed approaches, this participatory and iterative IBPA Framework provides guidance and direction for researchers, civil society, public health professionals and policy actors seeking to address the challenges of health inequities across diverse populations. Importantly, we present the application of the IBPA Framework in seven priority health-related policy case studies., Results: The analysis of each case study is focused on explaining how IBPA: 1) provides an innovative structure for critical policy analysis; 2) captures the different dimensions of policy contexts including history, politics, everyday lived experiences, diverse knowledges and intersecting social locations; and 3) generates transformative insights, knowledge, policy solutions and actions that cannot be gleaned from other equity-focused policy frameworks., Conclusion: The aim of this paper is to inspire a range of policy actors to recognize the potential of IBPA to foreground the complex contexts of health and social problems, and ultimately to transform how policy analysis is undertaken.

Routine HIV testing of all pregnant women in Oman has been introduced without prior knowledge of women's attitudes towards testing or their behaviour in the event of a positive test. This study recruited 1000 Omani pregnant women from antenatal clinics to explore their knowledge of HIV/AIDS, attitudes towards HIV testing and intended behaviours in the event of a positive test. Mother-to-child transmission was recognized by 86.6% of the women but only 21.0% knew that it was preventable and a few acknowledged the important role of antiviral drugs. Half of the women (51.9%) reported having been tested for HIV and 75.8% agreed about routine HIV testing for all pregnant women. A higher level of knowledge was significantly associated with a favourable intended behaviour related to voluntary testing, disclosure and seeking professional assistance in the event of a positive HIV test. The results are discussed in relation to opt-in and opt-out approaches to voluntary testing during pregnancy.

Introduction: Efforts to implement and take to scale highly efficacious, low-cost interventions to prevent mother-to-child HIV transmission (pMTCT) have been a cornerstone of reproductive health services in sub-Saharan Africa for over a decade. Yet efforts to increase access and utilization of these services remain far from optimal. This study developed and applied an approach to systematically classify pMTCT performance to identify modifiable health system factors associated with pMTCT performance which may be replicated in other pMTCT systems., Methods: Facility-level performance measures were collected at 30 sites over a 12-month period and reviewed for consistency. Five combinations of three indicators (1. HIV testing; 2. CD4 testing; 3. antiretroviral prophylaxis and combined antiretroviral therapy initiation) were compared including a composite of all three, a combination of 1. and 3., and each individually. Approaches were visually assessed to describe facility performance, focusing on rank order consistency across high, medium and low categories. Modifiable and non-modifiable factors were ascertained at each site and ranking process was reviewed to estimate association with facility performance through unadjusted Chi-square tests and logistic regression. After describing factors associated with high versus low performing pMTCT clinics, the effect of inclusion of the 10 middle performers was assessed., Results: The indicator most consistently associated with the reference composite indicator (HIV testing, antiretroviral prophylaxis and combined antiretroviral therapy) was the single measure of antiretroviral prophylaxis and combined antiretroviral therapy. Lower performing pMTCT clinics ranked consistently low across measurement strategies; high and middle performing clinics demonstrated more variability. Association between clinic characteristics and high pMTCT performance varied markedly across ranking strategies. Using the reference composite indicator, larger catchment area, higher number of institutional deliveries, onsite CD4 point-of-care capacity, and higher numbers of nurses and doctors were associated with high clinic performance while clinic location, NGO support, women's support group, community linkages patient-tracking systems and stock-outs were not associated with high performance., Conclusions: Classifying high and low performance provided consistent results across ranking measures, though granularity was improved by aggregating middle performers with either high or low performers. Human resources, catchment size and utilization were positively associated with effective pMTCT service delivery.

Objectives: The aim was to summarize national prevention of mother-to-child transmission (PMTCT) guidelines across Europe and to identify differences between these., Methods: A survey was conducted using a structured questionnaire sent to experts in 25 European countries from January to March 2012, requesting a copy of the national guidelines. Responses were received from 23 countries., Results: Twenty-two (96%) countries supported a policy to recommend antenatal HIV screening for all pregnant women (15: opt-out strategy; 8: opt-in strategy). For HIV-positive women in whom the only indication for antiretroviral therapy (ART) was PMTCT, the recommended gestational age for commencing ART varied from 12 to 28 weeks: initiation before 19 weeks gestation was recommended in guidelines from nine countries; in France, the UK and the Netherlands, there was a wide range, from 14 to 24 weeks, whereas the Swiss and Ukrainian guidelines recommended starting at 24-28 weeks and the German/Austrian and Lithuanian at 28 weeks. Six national guidelines recommended inclusion of Zidovudine in antenatal ART regimens, and seven (37%) allowed continuation of Efavirenz for women conceiving on this drug. According to nine guidelines, zidovudine should always be used intrapartum. Eighteen national guidelines stated that HIV-positive women on successful ART can have a vaginal delivery. Viral load thresholds for vaginal delivery were <1000 copies/ml in 5 countries, <400 copies/ml in 3 and <50 copies/ml in 11 countries., Conclusion: There are important differences across Europe in national PMTCT guidelines, with most variation seen where the evidence-base remains limited. Such differences should be considered when interpreting research and surveillance findings.

Background: The 2006 Centers for Disease Control and Prevention (CDC) revised recommendations for HIV testing in clinical settings contained seven specific changes to how health care facilities should provide HIV testing. These seven elements have been both supported and challenged in the lay and medical literature. Our first paper in BMC Medical Ethics presented an analysis of the three HIV testing procedural changes included in the recommendations. In this paper, we address the four remaining elements that concern HIV screening policy changes: (1) nontargeted HIV screening, (2) making HIV screening similar to screening for other treatable conditions, (3) increasing HIV screening without assured additional funding for linkage to care, and (4) making patients bear the costs of increased HIV screening in health care settings., Methods: We interviewed 25 members from the fields of US HIV advocacy, care, policy, and research about the ethical merits and demerits of the four changes to HIV screening policies. We performed a qualitative analysis of the participant responses in the interviews and summarized the major themes., Results: Participants commented that nontargeted HIV screening and making HIV screening similar to screening for other treatable medical conditions was ethical when it broadened the scope of people being tested for HIV. However, they believed it was unethical when it did not respect the exceptional nature of HIV and HIV testing. Some participants favored more testing regardless if there was assured additional funding for linkage to care or if patients might bear the costs of testing because they believed that merely alerting patients of their status was beneficial and would lead to positive consequences. Other participants found ethical flaws with testing without assured linkage to care and patients bearing the costs of testing, as this could discriminate against those who could not pay., Conclusions: Our findings suggest that there are fundamental ethical disagreements that shape views on CDC's recommended HIV testing policies. Differences remain on whether or not HIV remains an exceptional condition that requires it to be treated differently than other treatable conditions. Disagreement also exists on the responsibilities of health care providers and rights of patients in regards to screening in (1) the absence of assured linkage to care after an HIV diagnosis and (2) paying for the costs of HIV screening. Resolution of these disagreements is needed to serve the common goal of using testing to facilitate medical care for those who are HIV infected and for reducing HIV transmission.

Background: External quality assurance (EQA) programmes, which are routinely used in laboratories, have not been widely implemented for point-of- care tests (POCTs). A study was performed in ten health centres in Tanzania, to implement the use of dried blood spots (DBS) as an EQA method for HIV and syphilis (POCTs)., Method: DBS samples were collected for retesting at a reference laboratory and the results compared to the POCT results obtained at the clinic. In total, 2341 DBS samples were collected from 10 rural health facilities over a period of nine months, of which 92.5% were correctly collected and spotted., Results: The EQA method was easily implemented by healthcare workers under routine conditions in Northern Tanzania. For HIV, 967 out of 972 samples (99.5%) were concordant between DBS and POCT results. For syphilis, the sensitivity of syphilis tests varied between clinics with a median of 96% (25th and 75th quartile; 95-98%). The specificity of syphilis POCT was consistent compared to laboratory based test using DBS, with a median of 96% (25th and 75th quartiles; 95-98%)., Conclusion: Overall, the quality of testing varied at clinics and EQA results can be used to identify clinics where healthcare workers require remedial training, suggesting the necessity for stringent quality assurance programmes for POC testing. As Tanzania embarks on scaling up HIV and syphilis testing, DBS can be a useful and robust tool to monitor the quality of testing performed by healthcare workers and trigger corrective action to ensure accuracy of test results.

How can national AIDS program managers in low- and middle-income countries improve the coverage of HIV testing? In these countries heavily affected by HIV/AIDS, testing for HIV infection remains indeed critically infrequent with regard to its central role for individual care and control of the epidemic. Only 20 per cent of adults and 28 per cent of infants born from HIV-infected mothers are tested in a timely manner. The expansion of HIV testing is a prerequisite for reaching the World Health Organization's objective of universal access to HIV prevention, treatment, care, and support as well as the Millennium Development Goals related to HIV/AIDS and child mortality. The successful Rwandan experience of scaling up early infant HIV diagnosis brings hope for many countries.

Background: Adoption of CDC recommendations for routine, voluntary HIV screening of all Americans age 13–64 years has been slow. One method to increase adherence to clinical practice guidelines is through medical school and residency training., Objective: To explore the attitudes, barriers, and behaviors of clinician educators (CEs) regarding advocating routine HIV testing to their trainees., Design/participants: We analyzed CE responses to a 2009 survey of Society of General Internal Medicine members from community, VA, and university-affiliated clinics regarding HIV testing practices., Main Measures: Clinician educators were asked about their outpatient practices, knowledge and attitudes regarding the revised CDC recommendations and whether they encouraged trainees to perform routine HIV testing. Associations between HIV testing knowledge and attitudes and encouraging trainees to perform routine HIV testing were estimated using bivariate and multivariable logistic regression., Results: Of 515 respondents, 367 (71.3%) indicated they supervised trainees in an outpatient general internal medicine clinic. These CEs demonstrated suboptimal knowledge of CDC guidelines and over a third reported continued risk-based testing. Among CEs, 196 (53.4%) reported that they encourage trainees to perform routine HIV testing. Higher knowledge scores (aOR 5.10 (2.16, 12.0)) and more positive attitudes toward testing (aOR 8.83 (4.21, 18.5)) were independently associated with encouraging trainees to screen for HIV. Reasons for not encouraging trainees to screen included perceived low local prevalence (37.2%), competing teaching priorities (34.6%), and a busy clinic environment (34.0%)., Conclusions: Clinician educators have a special role in the dissemination of the CDC recommendations as they impact the knowledge and attitudes of newly practicing physicians. Despite awareness of CDC recommendations, many CEs do not recommend universal HIV testing to trainees. Interventions that improve faculty knowledge of HIV testing recommendations and address barriers in resident clinics may enhance adoption of routine HIV testing.

Background: Kenya experienced rapid scale up of HIV testing and counselling services in government health services from 2001. We set out to examine the human resource policy implications of scaling up HIV testing and counselling in Kenya and to analyse the resultant policy against a recognised theoretical framework of health policy reform (policy analysis triangle)., Methods: Qualitative methods were used to gain in-depth insights from policy makers who shaped scale up. This included 22 in-depth interviews with Voluntary Counselling and Testing (VCT) task force members, critical analysis of 53 sets of minutes and diary notes. We explore points of consensus and conflict amongst policymakers in Kenya and analyse this content to assess who favoured and resisted new policies, how scale up was achieved and the importance of the local context in which scale up occurred., Results: The scale up of VCT in Kenya had a number of human resource policy implications resulting from the introduction of lay counsellors and their authorisation to conduct rapid HIV testing using newly introduced rapid testing technologies. Our findings indicate that three key groups of actors were critical: laboratory professionals, counselling associations and the Ministry of Health. Strategic alliances between donors, NGOs and these three key groups underpinned the process. The process of reaching consensus required compromise and time commitment but was critical to a unified nationwide approach. Policies around quality assurance were integral in ensuring standardisation of content and approach., Conclusion: The introduction and scale up of new health service initiatives such as HIV voluntary counselling and testing necessitates changes to existing health systems and modification of entrenched interests around professional counselling and laboratory testing. Our methodological approach enabled exploration of complexities of scale up of HIV testing and counselling in Kenya. We argue that a better understanding of the diverse actors, the context and the process, is required to mitigate risks and maximise impact.

Objective: To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi., Design: A cross-sectional population survey of HIV infection, 2007 to 2008., Methods: Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected., Results: A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value., Conclusion: Face-to-face rapid testing by health personnel with minimum training at the client's home performs well when used on a wide scale in the community setting.

Background: The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates., Methods: We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study., Findings: Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [-15%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study., Interpretation: The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories.

An estimated one fourth of persons with human immunodeficiency virus (HIV) are not aware they are infected. Early diagnosis of HIV has the potential to ensure optimal outcomes for infected persons and to limit the spread of the virus. Important barriers to testing among physicians include insufficient time, reimbursement issues, and lack of patient acceptance. Current HIV testing guidelines address many of these barriers by making the testing process more streamlined and less stigmatizing. The opt-out consent process has been shown to improve test acceptance. Formal pretest counseling and written consent are no longer recommended by the Centers for Disease Control and Prevention. Nevertheless, pretest discussions provide an opportunity to give information about HIV, address fears of discrimination, and identify ongoing high-risk activities. With increased HIV screening in the primary care setting, more persons with HIV could be identified earlier, receive timely and appropriate care, and get treatment to prevent clinical progression and transmission.

Background: Cross-sectional surveys utilizing biomarkers that test for recent infection provide a convenient and cost effective way to estimate HIV incidence. In particular, the BED assay has been developed for this purpose. Controversy surrounding the way in which false positive results from the biomarker should be handled has lead to a number of different estimators that account for imperfect specificity. We compare the estimators proposed by McDougal et al., Hargrove et al. and McWalter & Welte., Methodology/principal Findings: The three estimators are analyzed and compared. An identity showing a relationship between the calibration parameters in the McDougal methodology is shown. When the three estimators are tested under a steady state epidemic, which includes individuals who fail to progress on the biomarker, only the McWalter/Welte method recovers an unbiased result., Conclusions/significance: Our analysis shows that the McDougal estimator can be reduced to a formula that only requires calibration of a mean window period and a long-term specificity. This allows simpler calibration techniques to be used and shows that all three estimators can be expressed using the same set of parameters. The McWalter/Welte method is applicable under the least restrictive assumptions and is the least prone to bias of the methods reviewed.

Objectives: We sought to provide a benchmark for human immunodeficiency virus (HIV) testing availability and practices in U.S. hospitals prior to the Centers for Disease Control and Prevention's (CDC's) 2006 revised recommendations., Methods: We conducted a survey of nonfederal general hospitals in the U.S. in 2004. Chi-square tests detected significant associations with hospital characteristics. Questionnaires were completed electronically via a secure Internet site or on paper. Nonresponse analysis was conducted and data were weighted to adjust for nonresponse., Results: HIV testing (on the basis of clinical symptoms or behavioral risk factors) was available in more than half of hospital inpatient units (62%), employee health departments (58%), and emergency departments (57%). Twenty-three percent offered routine screening (testing for people in a defined population regardless of clinical symptoms or behavioral risk), most commonly in labor and delivery. Teaching status, region, size, and type of metropolitan area were associated with the availability of HIV testing and routine screening (p<0.01). Hospitals used a variety of methods to link patients to care: referral to a hospital-based clinic (36%); on-site, same-day evaluation (35%); and referral to an unaffiliated HIV or community clinic (42%)., Conclusions: Hospitals offered HIV testing on the basis of clinical suspicion or risk, but were far from meeting CDC's current recommendation to routinely test all patients aged 13 to 64. Hospital size, teaching status, and geographic location were associated with HIV testing availability and testing practices. Our understanding of current practice identifies opportunities for public health action at the practitioner, organization, and systems levels.

The first HIV-1 marker that appears in blood following infection is HIV-1 RNA and usually the load is in millions of copies/ ml preceding seroconversion. A 24-year-old pregnant woman, gravida 2, parity 1 was tested for HIV as part of antenatal screening. Three samples were collected and tested from this individual over a period 70 days. The HIV-1 RNA level during seroconversion phase was very low, contrary to the well understood natural history of HIV infection. The reactivity rate in the ELISA and the Western Blot profile showed a gradual increase over the 70 days with a weak reactivity in a second generation assay (detects IgG only) for the third sample. This case illustrates the uncertainties regarding the serological window period in HIV infection and the need to use at least a third generation assay in testing centres for early detection of HIV infection.

Background: A comprehensive care and treatment program requires a well functioning laboratory services. We assessed satisfaction of medical personnel to the laboratory services to guide process of quality improvement of the services., Methodology: A cross-sectional survey in 24 randomly selected health facilities in Mainland Tanzania was conducted to assess the satisfaction of the medical personnel with the laboratory services., Results: Of 235 medical personnel interviewed, 196 were valid for analysis and about one quarter were dissatisfied with the laboratory services. Personnel dissatisfied with the services were 38.3% in timely test result, 24.5% in correct and accurate results and 22.4% in clear complete results. The personnel in public laboratories were more dissatisfied with timely test results (OR = 3.6, 95% CI 1.8, 7.3), correct results (OR = 4.1, 95% CI 1.6, 10.8) and clear complete results (OR = 5.0 95% CI 1.6, 15.2). Personnel dissatisfied with the services in 15 laboratories sending specimens to referral laboratories, varied from 13% in availability of equipment to 57% in timely results feedback from the referral laboratories. Personnel dissatisfied with the services in 14 referral laboratories, varied from 28.6% in properly identified specimen to 42.9% in clear, accurate test request and communication., Conclusion: About one quarter of medical personnel in sending or receiving laboratories were dissatisfied with the services. Comparing the personnel in public and private, the personnel in public laboratories were 4 times more dissatisfied with the timely test and correct results; and 5 times more dissatisfied with clear and complete test results.

Background: Patient's satisfaction with both private and public laboratory services is important for the improvement of the health care delivery in any country., Methods: A cross-sectional survey was conducted in 24 randomly selected health facilities with laboratories that are conducting HIV related testing, in Mainland Tanzania. The study assessed patient's satisfaction with the laboratory services where by a total of 295 patients were interviewed., Results: Of data analyzed for a varying totals from 224 to 294 patients, the percentage of dissatisfaction with both public and private laboratory services, ranged from 4.3% to 34.8%, with most of variables being more than 15%. Patients who sought private laboratory services were less dissatisfied with the cleanness (3/72, 4.2%) and the privacy (10/72, 13.9%) than those sought public laboratory service for the same services of cleanness (41/222, 18.5%) and privacy (61/222, 27.5%), and proportional differences were statistically significant (X2 = 8.7, p = 0.003 and X2 = 5.5, p = 0.01, respectively). Patients with higher education were more likely to be dissatisfied with privacy (OR = 1.8, 95% CI: 1.1-3.1) and waiting time (OR = 2.5, 95% CI: 1.5 - 4.2) in both private and public facilities. Patients with secondary education were more likely to be dissatisfied with the waiting time (OR = 5.2; 95%CI: 2.2-12.2) and result notification (OR = 5.1 95%CI (2.2-12.2) than those with lower education., Conclusion: About 15.0% to 34.8% of patients were not satisfied with waiting time, privacy, results notification cleanness and timely instructions. Patients visited private facilities were less dissatisfied with cleanness and privacy of laboratory services than those visited public facilities. Patients with higher education were more likely to be dissatisfied with privacy and waiting time in both private and public facilities.

Background: Although the benefits of identifying and treating asymptomatic HIV-infected individuals are firmly established, health care providers often miss opportunities to offer HIV-testing., Objective: To evaluate whether a multi-component intervention increases the rate of HIV diagnostic testing., Design: Pre- to post-quasi-experiment in 5 Veterans Health Administration facilities. Two facilities received the intervention; the other three facilities were controls. The intervention included a real-time electronic clinical reminder that encourages HIV testing, and feedback reports and a provider activation program., Patients: Persons receiving health care between August 2004 and September 2006 who were at risk but had not been previously tested for HIV infection., Measurements: Pre- to post-changes in the rates of HIV testing at the intervention and control facilities, Results: At the two intervention sites, the adjusted rate of testing increased from 4.8% to 10.8% and from 5.5% to 12.8% (both comparisons, p < .001). In addition, there were 15 new diagnoses of HIV in the pre-intervention year (0.46% of all tests) versus 30 new diagnoses in the post-intervention year (0.45% of all tests). No changes were observed at the control facilities., Conclusions: Use of clinical reminders and provider feedback, activation, and social marketing increased the frequency of HIV testing and the number of new HIV diagnoses. These findings support a multimodal approach toward achieving the Centers for Disease Control and Prevention's goal of having every American know their HIV status as a matter of routine clinical practice.

Objective: To identify discriminatory attitudes in two moments of the Brazilian HIV/AIDS epidemic, as well as the occurrence of possible changes., Methods: The Intention of Discrimination Index was obtained by scoring 1 for discriminatory situations or 0, when the opposite was the case. Intention of discrimination ranges were established by means of the clustering technique, and made compatible between the 1998 and 2005 surveys. Mean comparisons, chi-square test and ordered logit adjusted regression models were used to verify association between the index and socio-demographic variables., Results: Between the 1998 and 2005 surveys, there was a statistically significant reduction in the proportion of people who answered "yes" to anti-HIV test's being mandatory in the following cases: admission for employment, before getting married, when joining the military service, drug users, foreigners entering the country, sex professionals, and for all the people. To have lower level of education, to be female, to live in the North/Northeast regions of Brazil, and to be aged over 45 years are factors associated with higher intention of discrimination level., Conclusions: The growth of intention of discrimination shows that information about ways of AIDS transmission and non-transmission still needs to be better planned and promoted, especially among populations that have lower level of education, live in the North/Northeast regions, are female and aged over 45 years.

This supplement was developed from a national meeting entitled "Opportunities for Improving HIV Diagnosis, Prevention & Access to Care in the U.S.," held 29-30 November 2006 in Washington, D.C. Leaders in the fight against human immunodeficiency virus (HIV) infection were recruited from areas of government, academia, clinical medicine, patient advocacy, and private industry to discuss the following ambitious topics: (1) strategies to significantly reduce overall HIV transmission rates in the United States, (2) methods to identify the estimated 250,000 individuals in the United States who remain unaware of their positive HIV serostatus, so they can be offered treatment earlier in the course of their disease, and (3) obstacles associated with opt-out HIV testing, including limits on resources for treatment of HIV infection. We served as cochairs for the meeting and, in conjunction with a scientific planning committee we appointed, oversaw the selection of the articles published in this supplement. Cumulatively, the articles address the stated topics by identifying methods to ensure the success of more-aggressive HIV testing measures, such as those described in the September 2006 recommendations of the Centers for Disease Control and Prevention; examining the success of current measures to prevent HIV infection such that future strategies can be improved; identifying the methods that will foster earlier diagnosis and access to treatment for individuals with HIV infection; and determining the limitations in human and financial resources to adequately care for a surge in the number of individuals with newly diagnosed HIV infection.

New guidelines from the Centers for Disease Control and Prevention recommend that opt-out screening for human immunodeficiency virus (HIV) without written patient consent be part of routine clinical care and imply that state HIV-associated laws in conflict with this approach should be amended. However, HIV testing and treatment issues are governed by a range of federal and state laws, common law principles, constitutional provisions, and various codes of ethics. Patient testing protocols should satisfy the legal definition of informed consent, to reduce risk of liability for providers (i.e., health care professionals and facilities). Rigid application of the new guidelines may trigger legal claims, especially if there is no link to care for persons with a positive test result, no proof of informed consent, or inadequate counseling. Ensuring confidentiality, better test training for providers, and provider collaboration with HIV service organizations can reduce the risk of patient claims, but state and federal laws, codes of ethics, and concerns about provider liability should temper reflexive wholesale adoption of guidelines that recommend opt-out screening.

The recommendations for human immunodeficiency virus (HIV) testing in the United States were recently revised. An important goal of these revisions is to reduce the proportion of individuals infected with HIV who are unaware of their infection. In the new guidelines, screening is recommended for all individuals aged 13-64 years in any health care setting, provided that they are notified that testing will be performed and do not decline testing. It was further recommended that individuals at high risk for HIV infection be screened annually. Through wider screening, the identification of persons with unrecognized HIV is expected to facilitate treatment and allow better targeting of HIV prevention strategies.

Persons with or at risk for human immunodeficiency virus (HIV) infection need client-centered counseling and information about the disease. One of the best opportunities to provide counseling and information is during an HIV testing encounter. New testing guidelines from the Centers for Disease Control and Prevention encourage less counseling before and after testing. We review the evidence regarding voluntary counseling and testing (VCT). There is clear endorsement in peer-reviewed scientific journals for VCT as part of an evidence-based bundle of interventions to prevent HIV infection. For persons who test seropositive, VCT has an impact, but it is hard to uncouple the impact of counseling from that of testing. For persons who test seronegative, counseling in clinical settings has a beneficial impact on risk behaviors and sexually transmitted disease incidence and costs very little to implement. In settings where "typical" counseling is not up to client-centered counseling standards, it should be improved, not abandoned, but we may need to recruit community service organizations and nonclinicians in the health care system to achieve this aim.

On September 22, 2006, the Centers for Disease Control and Prevention (CDC) announced recommendations to expand the role of health-care providers in human immunodeficiency virus (HIV) testing. These clearlyjustified guidelines aim to remove traditional testing barriers, and thereby increase the rate of earlier diagnosis. This overarching strategy to increase testing in all health-care settings also includes less traditional sites such as emergency departments and correctional health-care facilities. The motivation for the guidelines is intuitive, as the need for augmented testing is well supported. Of those infected with HIV in the U.S., approximately one-quarter are unaware of their disease status. People who are unaware of their infection disproportionately account for new transmissions and are unable to benefit from treatment. The HIV incidence has not fallen below approximately 40,000 new diagnoses per year, of which approximately 40% are diagnosed late in the course of infection. Universal screening, even in populations with a disease prevalence of 0.1%, has been shown to be cost-effective. While the guidelines have been reviewed in depth, current interpretations do not adequately outline a structure for further debate or facilitate incremental or partial implementation of the recommendations. This must be remedied, as comprehensive implementation of the guidelines will be controversial or logistically impossible in many settings for the foreseeable future. Herein, we provide a clarified interpretation by outlining the core guideline elements individually and within the context of current barriers to implementation. We then discuss potential combinations of the core elements that would enable increased testing in settings where comprehensive guideline implementation is not possible.

In September 2006, the Centers for Disease Control and Prevention released its revised recommendations for human immunodeficiency virus (HIV) testing. Prominent among these were the recommendations that emergency departments should perform routine screening for HIV infection. This report outlines the steps needed to set up an emergency department-based HIV screening program based on these guidelines. It contains the lessons that were learned when such a program was initiated at an academic emergency department. Consideration of these steps will help streamline the establishment of the program, but there should be careful consideration of the program's costs and sustainability before embarking on the process.