Pooling Strategies for Screening Blood in Areas with Low Prevalence of HIV

Human immunodeficiency virus (HIV) infection has serious consequences and must be kept out of blood supplies. Screening to ensure the safety of blood supplies is associated with a very high cost. The idea of pooling test samples to obtain significant savings was first suggested in 1943. Recently pooling sera has gained wider interest both as a means to determine the HIV seroprevalence rate in general populations and to weed out all HIV-positive units in blood supplies. We describe a simple method for detecting seropositive samples in mass screening. This method determines the pooling size based on the estimated prevalence rate. Although several repooling stages are allowed, these will be kept to a minimum since the more stages that are required, the greater chance for human and technical errors. The criteria to end pooling are based on both the savings rate and the relative cost between the preparation and the actual test. Two examples illustrate the applications of this method in determining the number of samples to be pooled in successive stages and the resulting savings rate.     

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.     

Risk of HIV infection from transfusion with blood negative for HIV antibody in a west African city.

OBJECTIVE--To estimate the risk of infection with HIV (HIV 1 or HIV 2, or both) from transfusion of a screened unit of blood in a high prevalence area in west Africa. DESIGN--Retrospective cohort study for January-July 1991. SETTING--National Blood Transfusion Centre, Abidjan, Côte d''Ivoire. SUBJECTS--Repeat donors (5831 units of blood) and first time donors (5076 units) in the first five months of 1991. MAIN OUTCOME MEASURES--Prevalence and estimated incidence of HIV infection in repeat and first time donors; estimated rate of potentially infected, HIV antibody negative units; and rate of (false negative) potentially infected units assuming a laboratory test sensitivity of 99%. RESULTS--Overall HIV prevalence was 11.0% in first time donors and 2.1% in repeat donors. In the first seven months of 1991, 29 HIV antibody positive (27 HIV 1, 1 HIV 2, 1 dually reactive) donors with a seronegative unit of blood earlier in the year were identified; 26 had donated blood eight weeks or less before their estimated dates of seroconversion and may have been infectious (minimum rate 26/5831 (4.5/1000 potentially infected units)). Estimated incidence of infection in repeat donors was 1.2-2.5%. Laboratory test insensitivity would result in an estimated 1.1/1000 false negative units from first time donors and 0.2/1000 units from regular donors. The overall rate of potentially infected units (all donors, seroconversions, and errors) was estimated at 5.4-10.6/1000. CONCLUSIONS--The risk of HIV infection from a single unit of blood remains substantial (5.4-10.6/1000 units). To prevent infection from blood transfusion in areas of high incidence and prevalence of HIV all but absolutely essential transfusions should be avoided, and donors with low incidence of HIV infection should be selected.     

Initial Health Assessments and HIV Screening under the Affordable Care Act

Background

The Centers for Disease Control and Prevention (CDC) estimates that 156,300 (95% CI 144,100–165,900) Americans living with HIV in 2012 were unaware of their infection. To increase knowledge of HIV status, CDC guidelines seek to make HIV screening a routine part of medical care. This paper examines how routinely California primary care providers test for HIV and how providers’ knowledge of California’s streamlined testing requirements, use of sexual histories, and having an electronic medical record prompt for HIV testing, relate to test offers.

Methods

We surveyed all ten California health plans offered under health reform’s Insurance Exchange (response rate = 50%) and 322 primary care providers to those plans (response rate = 19%) to assess use of HIV screening and risk assessments.

Results

Only 31.7% of 60 responding providers reported offering HIV tests to all or most new enrollees and only 8.8% offered an HIV test of blood samples all or most of the time despite the California law requiring that providers offer HIV testing of blood samples in primary care settings. Twenty-eight of the 60 providers (46.6%) were unaware that California had reduced barriers to HIV screening by eliminating the requirement for written informed consent and pre-test counseling. HIV screening of new enrollees all or most of the time was reported by 53.1% of the well-informed providers, but only 7.1% of the less informed providers, a difference of 46 percentage points (95% CI: 21.0%—66.5%). Providers who routinely obtained sexual histories were 29 percentage points (95% CI: 0.2%—54.9%) more likely to screen for HIV all or most of the time than those who did not ask sexual histories.

Conclusion

Changing HIV screening requirements is important, but not sufficient to make HIV testing a routine part of medical care. Provider education to increase knowledge about the changed HIV testing requirements could positively impact testing rates.     

Hold everything! Holding policies for protecting plasma supplies

In spite of advances in testing technologies for detecting infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), occasionally blood or plasma is collected that is potentially infectious, but is not detected as such by existing screening tests. We consider the effect of a holding policy for further reducing the number of potentially infectious units that are released for fractionation. The policy dictates a holding period during which all donated units are stored. If a donor tests positive for the infection in question at a subsequent donation, then all of that donor's units currently in storage are discarded. Otherwise, donated units are released at the end of the holding period. In the case of a single disease, we determine optimal holding periods as well as policies that are as effective as the best screening tests currently available.     

HIV-1 testing: product development strategies.

Strategies for the development of diagnostic products for acquired immune deficiency syndrome (AIDS) are inextricably linked to the status of our knowledge of the human immunodeficiency virus (HIV) and the events associated with the pathogenesis of AIDS. This review traces product development strategies from 1984 to the present day. Product development activities in the HIV-1 antibody screening test market were a response to the need to remove contaminated units from the blood supply. With the successes in screening blood and blood products, there has been a shift towards product development for personal health care and applicant suitability. Identification of markers for disease progression and the need to monitor therapeutic efficacy is now leading to tests for patient disease staging, monitoring and prognosis.     

Cost-Effectiveness of Enhanced Syphilis Screening among HIV-Positive Men Who Have Sex with Men: A Microsimulation Model

Background

Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM). Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population.

Purpose

We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care.

Methods

We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually) to different combinations of more frequent (3- or 6-monthly) screening and higher coverage (100% screened). We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer.

Results

Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months) were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV.

Conclusions

We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement for regular blood testing in this group (i.e., for viral load monitoring) makes intensification of syphilis screening appear readily practicable.     

Estimating the distribution of a renewal process from times at which events from an independent process are detected

The analysis of length-biased data has been mostly limited to the interarrival interval of a renewal process covering a specific time point. Motivated by a surveillance problem, we consider a more general situation where this time point is random and related to a specific event, for example, status change or onset of a disease. We also consider the problem when additional information is available on whether the event intervals (interarrival intervals covering the random event) end within or after a random time period (which we call a window period) following the random event. Under the assumptions that the occurrence rate of the random event is low and the renewal process is independent of the random event, we provide formulae for the estimation of the distribution of interarrival times based on the observed event intervals. Procedures for testing the required assumptions are also furnished. We apply our results to human immunodeficiency virus (HIV) test data from public test sites in Seattle, Washington, where the random event is HIV infection and the window period is from the onset of HIV infection to the time at which a less sensitive HIV test becomes positive. Results show that the estimator of the intertest interval length distribution from event intervals ending within the window period is less biased than the estimator from all event intervals; the latter estimator is affected by right truncation. Finally, we discuss possible applications to estimating HIV incidence and analyzing length-biased samples with right or left truncated data.     

More Powerful Likelihood Ratio Tests for Isotonic Binomial Proportions

Binomial group testing involves pooling individuals into groups and observing a binary response on each group. Results from the group tests can then be used to draw inference about population proportions. Its use as an experimental design has received much attention in recent years, especially in public‐health screening experiments and vector‐transfer designs in plant pathology. We investigate the benefits of group testing in situations wherein one desires to test whether or not probabilities are increasingly ordered across the levels of an observed qualitative covariate, i.e., across strata of a population or among treatment levels. We use a known likelihood ratio test for individual testing, but extend its use to group‐testing situations to show the increases in power conferred by using group testing when operating in this constrained parameter space. We apply our methods to data from an HIV study involving male subjects classified as intraveneous drug users.     

HIV Testing among Outpatients with Medicaid and Commercial Insurance

Objective

To assess HIV testing and factors associated with receipt of testing among persons with Medicaid and commercial insurance during 2012.

Methods

Outpatient and laboratory claims were analyzed from two databases: all Medicaid claims from six states and all claims from Medicaid health plans from four other states and a large national convenience sample of patients with commercial insurance in the United States. We excluded those aged <13 years and >64 years, enrolled <9 of the 12 months, pregnant females, and previously diagnosed with HIV. We identified patients with new HIV diagnoses that followed (did not precede) the HIV test, using HIV ICD-9 codes. HIV testing percentages were assessed by patient demographics and other tests or diagnoses that occurred during the same visit.

Results

During 2012, 89,242 of 2,069,536 patients (4.3%) with Medicaid had at least one HIV test, and 850 (1.0%) of those tested received a new HIV diagnosis. Among 27,206,804 patients with commercial insurance, 757,646 (2.8%) had at least one HIV test, and 5,884 (0.8%) of those tested received a new HIV diagnosis. During visits that included an HIV test, 80.2% of Medicaid and 83.0% of commercial insurance claims also included a test or diagnosis for a sexually transmitted infection (STI), and/or Hepatitis B or C virus at the same visit.

Conclusions

HIV testing primarily took place concurrently with screening or diagnoses for STIs or Hepatitis B or C. We found little evidence to suggest routine screening for HIV infection was widespread.     

NAT: Perspectives for Cellular Components

The introduction of routine testing to detect viral genomes in donated blood was originally driven by requirements for plasma fractionation in relation to exclusion of hepatitis C virus (HCV) RNA. Nevertheless, it was obvious from the outset that a dual standard for fractionated products and individual blood components would be untenable. In many countries therefore, planning for introduction of nucleic acid testing (NAT) of blood incorporated progression to release of HCV RNA tested components. HCV was singled out because of its long seronegative 'window period', relatively high prevalence and incidence in blood donors, rapid burst time and high genome copy number during seroconversion. The latter properties made HCV particularly suitable for detection in pools of samples. If HCV RNA testing is required for release of labile components such as platelets, rapid provision of NAT results is vital because of short shelf life of platelets and the problems of delays when resolving the infectious unit in a reactive pool. For NAT release of labile components smaller sample pool sizes allow faster resolution of RNA positive units. Smaller pools involve high test throughput, the likely need for more testing laboratories and ensuing increased costs. Single sample testing is the ultimate extrapolation of reducing sample pool size. With reduced pool sizes or single sample testing, the option of testing for other viruses (e.g. HIV or HBV) singly or in multiplex also arises. The cost-benefit and incremental yield of such strategies in the light of 'combo' assays for HIV Ag/Ab and the recently described HCV Ag assay will require careful and objective assessment, together with re-appraisal of anti-HBc screening for detection of HBV infected donors at the "tail-end" of carriage.     

多重环介导核酸等温扩增技术检测血液中常见病原体

背景：血液安全性筛查是输血前必要检测项目。目前临床采用血清学检测技术,存在较长的检测窗口期,易产生假阴性检测结果,造成输血交叉感染。目的：建立多重环介导核酸等温扩增技术,实现在一管反应体系内同时检测四种病原体：乙肝病毒,丙肝病毒,艾滋病毒和梅毒螺旋体。方法：通过限制性酶切处理多重环介导核酸等温扩增产物,利用酶切产物的长度分析扩增产物的种类,从而分析待测样本中含有何种血液病原体。结果：检测164例临床样本,其检测结果可以通过琼脂糖电泳,聚丙烯酰胺凝胶电泳及芯片电泳分析,且均可实现对多重扩增产物的酶切片段进行区分和鉴别。结论：多重环介导核酸等温扩增技术可以同时单管检测多种待测血液病原体,可以为临床提高简单、快速、高灵敏和高特异的检测技术。     

Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness

Objective

To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening.

Design

We used Portuguese national clinical and economic data to conduct a model-based assessment.

Methods

We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness.

Results

One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively.

Conclusions

One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal’s challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings.     

Opt-out of voluntary HIV testing: a Singapore hospital's experience

Introduction

Since 2008, the Singapore Ministry of Health (MOH) has expanded HIV testing by increasing anonymous HIV test sites, as well as issuing a directive to hospitals to offer routine voluntary opt out inpatient HIV testing. We reviewed this program implemented at the end of 2008 at Tan Tock Seng Hospital (TTSH), the second largest acute care general hospital in Singapore.

Methods and Findings

From January 2009 to December 2010, all inpatients aged greater or equal than 21 years were screened for HIV unless they declined or were not eligible for screening. We reviewed the implementation of the Opt Out testing policy. There were a total of 93,211 admissions; 41,543 patients were included based on HIV screening program eligibility criteria. Among those included, 79% (n = 32,675) opted out of HIV screening. The overall acceptance rate was 21%. Majority of eligible patients who were tested (63%) were men. The mean age of tested patients was 52 years. The opt out rate was significantly higher among females (OR: 1.5, 95%CI: 1.4–1.6), aged >60 years (OR: 2.3, 95%CI: 2.2–2.4) and Chinese ethnicity (OR: 1.7, 95%CI:1.6–1.8). The false positive rate of the HIV screening test is 0.56%. The proportion of patients with HIV infection among those who underwent HIV screening is 0.18%. All16 confirmed HIV patients were linked to care.

Conclusion

The default opt-in rate of inpatient HIV testing was low at Tan Tock Seng Hospital, Singapore. Efforts to address individual HIV risk perception and campaigns against HIV stigma are needed to encourage more individuals to be tested for HIV.     

Evaluation of a HIV Voluntary Opt-Out Screening Program in a Singapore Hospital

Background

Early diagnosis of human immunodeficiency virus (HIV) allows for appropriately timed interventions with improved outcomes, but HIV screening among asymptomatic persons and the general population in Singapore remains low. In 2008, Singapore’s Ministry of Health implemented HIV voluntary opt-out screening (VOS) for hospitalised adults. We evaluated the outcome of VOS and surveyed reasons for its low uptake in our institution.

Methods

We assessed the outcomes of the VOS programme from January 2010 to December 2013 at National University Hospital, a 1081-bed tertiary hospital in Singapore. We also examined reasons for opting-in and opting-out using an interviewer–administered structured questionnaire in a representative sample in January 2013.

Results

107,523 patients fulfilled VOS criteria and were offered HIV screening, of which 5215 (4.9%) agreed to testing. 4850 (93.1%) of those who opted-in had an HIV test done. Three (0.06%) tested positive for HIV. 238 patients (14.2%) were surveyed regarding reasons for opting-in or out of VOS. 21 (8.8%) had opted-in. Patients who opted-in were likely to be younger, more educated and reported having more regular sexual partners. Type of housing, number of casual sexual partners, sexual orientation, intravenous drug use, condom use and previous sexually transmitted infection were not associated with deciding to opt-in/out. Patients’ most common reasons for opting-out were: belief that they were at low risk (50.2%), belief that they were too old (26.8%), cost (6.9%) and aversion to venepuncture (6.5%). The most common reason for opting-in was desire to know their HIV status (47.6%).

Conclusion

The success of an HIV-VOS program is largely determined by test uptake. Our study showed that the majority of eligible VOS patients opted-out of HIV screening. Given the considerable cost and low yield of this programme, more needs to be done to better equip patients in self-risk assessment and opting in to testing.     

South East Asia faces severe shortage of safe blood

South East Asia is experiencing a severe shortage of safe blood. The region collects only 7 million units a year but needs a total of 15 million units. This problem is worsened by inappropriate use of blood without separation into its components, with 80-85% of blood being used as whole blood. In addition, the Supreme Court in India has banned the use of blood from professional blood sellers because they were considered to be a high-risk group of HIV. Unscreened blood is also allowed to flourish in both Bangladesh and Pakistan because these countries do not have any national blood policy. Moreover, even with blood screening in India, hepatitis B and C are present because the virus is not tested in this country. In the screened blood in India, the seroprevalence of hepatitis B is 0.06-8.5% and that of hepatitis C is 1.2-3%. While in Islamabad, Pakistan, testing results showed that 8.1% of blood was infected with hepatitis C. Lastly, 5-10% of HIV infections in Southeast Asia are transfusion-induced.     

Twelve Months of Routine HIV Screening in 6 Emergency Departments in the Paris Area: Results from the ANRS URDEP Study

Objective

In October 2009 the French National Authority for Health recommended that HIV testing be proposed at least once to all persons aged 15 to 70 years in all healthcare settings. We examined whether routine HIV screening with a rapid test in emergency departments (EDs) was feasible without dedicated staff, and whether newly diagnosed persons could be linked to care.

Methods

This one-year study started in December 2009 in 6 EDs in the Paris area, using the INSTI™ test. Eligible individuals were persons 18 to 70 years old who did not present for a vital emergency, for blood or sexual HIV exposure, or for HIV screening. Written informed consent was required.

Results

Among 183 957 eligible persons, 11 401 were offered HIV testing (6.2%), of whom 7936 accepted (69.6%) and 7215 (90.9%) were tested (overall screening rate 3.9%); 1857 non eligible persons were also tested. Fifty-five new diagnoses of HIV infection were confirmed by Western blot (0.61% (95% CI 0.46–0.79). There was one false-positive rapid test result. Among the newly diagnosed persons, 48 (87%) were linked to care, of whom 36 were not lost to follow-up at month 6 (75%); median CD4 cell count was 241/mm³ (IQR: 52–423/mm³).

Conclusions

Screening rates were similar to those reported in opt-in studies with no dedicated staff. The rate of new diagnoses was similar to that observed in free anonymous test centres in the Paris area, and well above the prevalence (0.1%) at which testing has been shown to be cost-effective.     

Postnatal human immunodeficiency virus antibody testing. The effects of current policy on infant care and maternal informed consent.

Routine human immunodeficiency virus (HIV) antibody screening of umbilical cord blood identifies neonates at risk for HIV infection but may hold risks as well as benefits for infants and mothers. We describe the effect of testing on infant placement and care and report the women''s understanding of pretest counseling and consent. In a case-control analysis of 327 tested infants, seropositive infants (13) had a higher rate of discharge to home (62%) than did controls (31%). More case infants (100%) received follow-up care and vaccinations than control infants (46%). Of 32 women interviewed after HIV antibody test informed consent, only 31% understood that a positive cord blood test result was inconclusive for the infant, and most (78%) did not identify any associated socioeconomic risks. Most (88%) stated an interest in learning their serostatus, but only 22% returned for test results. Despite the benefits of HIV antibody testing of at-risk infants, current testing and counseling procedures inadequately inform women, limiting the testing benefits to them.     

Hepatitis B antigen in screened blood units for transfusion in renal dialysis patients

Blood units for transfusion are screened routinely in Ontario for the presence of hepatitis B antigen (HB-Ag) by counter-immunoelectrophoresis (CIEP). Since the radioimmunoassay (RIA) method is more sensitive for this purpose we used it to test blood units delivered to the hospital''s Renal Dialysis Unit in order to determine if HB-Ag-carrying blood donors were being missed by the less sensitive CIEP method.Out of the 606 blood units tested, eight were found to contain HB-Ag, an incidence of 13 out of 1000 donors. This finding indicates that the counter-immunoelectrophoresis method is insufficiently sensitive as a safe screening method for detection of hepatitis antigen.