Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants

IntroductionLive attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1).Methods420 mother-child pairs were recruited at infant age 6–12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion.ResultsBaseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68–0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01).ConclusionLow immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research

Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection

Background Accurate rapid diagnostic tests for SARS‐CoV‐2 infection could contribute to clinical and public health strategies to manage the COVID‐19 pandemic. Point‐of‐care antigen and molecular tests to detect current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission. Objectives To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Search methods Electronic searches of the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID‐19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions. Selection criteria We included studies of people with either suspected SARS‐CoV‐2 infection, known SARS‐CoV‐2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established diagnostic criteria). Data collection and analysis Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS‐2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular‐based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. Main results Seventy‐eight study cohorts were included (described in 64 study reports, including 20 pre‐prints), reporting results for 24,087 samples (7,415 with confirmed SARS‐CoV‐2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (37%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (37%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS‐CoV‐2 based on a single RT‐PCR result, and none included participants meeting case definitions for probable COVID‐19. Antigen tests Forty‐eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self‐testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer’s instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset. Authors' conclusions Antigen tests vary in sensitivity. In people with signs and symptoms of COVID‐19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID‐19 diagnostics (‘acceptable’ sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory‐based RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT‐PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self‐testing) are required

Antibody tests for identification of current and past infection with SARS-CoV-2

Background The diagnostic challenges associated with the COVID‐19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS‐CoV‐2 infection. Serology tests to detect the presence of antibodies to SARS‐CoV‐2 enable detection of past infection and may detect cases of SARS‐CoV‐2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS‐CoV‐2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS‐CoV‐2 epidemiology. Objectives To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS‐CoV‐2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS‐CoV‐2. Sources of heterogeneity investigated included: timing of test, test method, SARS‐CoV‐2 antigen used, test brand, and reference standard for non‐SARS‐CoV‐2 cases. Search methods The COVID‐19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co‐ordinating Centre (EPPI‐Centre) ‘COVID‐19: Living map of the evidence’ and the Norwegian Institute of Public Health ’NIPH systematic and living map on COVID‐19 evidence’. We did not apply language restrictions. Selection criteria We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT‐PCR test. Small studies with fewer than 25 SARS‐CoV‐2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction tests (RT‐PCR), clinical diagnostic criteria, and pre‐pandemic samples). Data collection and analysis We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS‐2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta‐analysis, we fitted univariate random‐effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random‐effects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria. Main results We included 178 separate studies (described in 177 study reports, with 45 as pre‐prints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARS‐CoV‐2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARS‐CoV‐2 infection were most commonly hospital inpatients (78/178, 44%), and pre‐pandemic samples were used by 45% (81/178) to estimate specificity. Over two‐thirds of studies recruited participants based on known SARS‐CoV‐2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARS‐CoV‐2 vaccines and present data for naturally acquired antibody responses. Seventy‐nine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzyme‐linked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%). Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies. Average sensitivities for current SARS‐CoV‐2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot. Average specificities were consistently high and precise, particularly for pre‐pandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies). Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescent‐phase infection) and specific (pre‐pandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spike‐protein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescent‐phase infection. Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity. In a low‐prevalence (2%) setting, where antibody testing is used to diagnose COVID‐19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARS‐CoV‐2 infection. In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days post‐symptom onset or post‐positive PCR) of SARS‐CoV‐2 infection. Authors' conclusions Some antibody tests could be a useful diagnostic tool for those in whom molecular‐ or antigen‐based tests have failed to detect the SARS‐CoV‐2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post‐acute sequelae of COVID‐19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero‐epidemiological purposes. The applicability of results for detection of vaccination‐induced antibodies is uncertain

A pilot randomized trial of incentive strategies to promote HIV retesting in rural Uganda.

BACKGROUND:Retesting for HIV is critical to identifying newly-infected persons and reinforcing prevention efforts among at-risk adults. Incentives can increase one-time HIV testing, but their role in promoting retesting is unknown. We sought to test feasibility and acceptability of incentive strategies, including commitment contracts, to promote HIV retesting among at-risk adults in rural Uganda. METHODS:At-risk HIV-negative adults were enrolled in a pilot trial assessing feasibility and acceptability of incentive strategies to promote HIV retesting three months after enrollment. Participants were randomized (1:1:3) to: 1) no incentive; 2) standard cash incentive (~US$4); and 3) commitment contract: participants could voluntarily make a low- or high-value deposit that would be returned with added interest (totaling ~US$4 including the deposit) upon retesting or lost if participants failed to retest. Contracts sought to promote retesting by leveraging loss aversion and addressing present bias via pre-commitment. Outcomes included acceptability of trial enrollment, contract feasibility (proportion of participants making deposits), and HIV retesting uptake. RESULTS:Of 130 HIV-negative eligible adults, 123 (95%) enrolled and were randomized: 74 (60%) to commitment contracts, 25 (20%) to standard incentives, and 24 (20%) to no incentive. Of contract participants, 69 (93%) made deposits. Overall, 93 (76%) participants retested for HIV: uptake was highest in the standard incentive group (22/25 [88%]) and lowest in high-value contract (26/36 [72%]) and no incentive (17/24 [71%]) groups. CONCLUSION:In a randomized trial of strategies to promote HIV retesting among at-risk adults in Uganda, incentive strategies, including commitment contracts, were feasible and had high acceptability. Our findings suggest use of incentives for HIV retesting merits further comparison in a larger trial. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT:02890459

A pilot randomized trial of incentive strategies to promote HIV retesting in rural Uganda.

BackgroundRetesting for HIV is critical to identifying newly-infected persons and reinforcing prevention efforts among at-risk adults. Incentives can increase one-time HIV testing, but their role in promoting retesting is unknown. We sought to test feasibility and acceptability of incentive strategies, including commitment contracts, to promote HIV retesting among at-risk adults in rural Uganda.MethodsAt-risk HIV-negative adults were enrolled in a pilot trial assessing feasibility and acceptability of incentive strategies to promote HIV retesting three months after enrollment. Participants were randomized (1:1:3) to: 1) no incentive; 2) standard cash incentive (~US$4); and 3) commitment contract: participants could voluntarily make a low- or high-value deposit that would be returned with added interest (totaling ~US$4 including the deposit) upon retesting or lost if participants failed to retest. Contracts sought to promote retesting by leveraging loss aversion and addressing present bias via pre-commitment. Outcomes included acceptability of trial enrollment, contract feasibility (proportion of participants making deposits), and HIV retesting uptake.ResultsOf 130 HIV-negative eligible adults, 123 (95%) enrolled and were randomized: 74 (60%) to commitment contracts, 25 (20%) to standard incentives, and 24 (20%) to no incentive. Of contract participants, 69 (93%) made deposits. Overall, 93 (76%) participants retested for HIV: uptake was highest in the standard incentive group (22/25 [88%]) and lowest in high-value contract (26/36 [72%]) and no incentive (17/24 [71%]) groups.ConclusionIn a randomized trial of strategies to promote HIV retesting among at-risk adults in Uganda, incentive strategies, including commitment contracts, were feasible and had high acceptability. Our findings suggest use of incentives for HIV retesting merits further comparison in a larger trial.Trial registrationClinicalTrials.gov identifier: NCT:02890459

Comparative effectiveness of novel nonmonetary incentives to promote HIV testing.

OBJECTIVE:To assess the comparative effectiveness of alternative incentive-based interventions to promote HIV testing among men. DESIGN:Randomized clinical trial. METHODS:We enumerated four Ugandan parishes and enrolled men at least 18 years. Participants were randomized to six groups that received incentives of varying type and amount for HIV testing at a 13-day community health campaign. Incentive types were: gain-framed (control): participants were told they would receive a prize for testing; loss-framed: participants were told they had won a prize, shown several prizes, asked to select one, then told they would lose the prize if they did not test; lotteries: those who tested had a chance to win larger prizes. Each incentive type had a low and high amount (∼US$1 and US$5/participant). The primary outcome was HIV-testing uptake at the community health campaign. RESULTS:Of 2532 participants, 1924 (76%) tested for HIV; 7.6% of those tested were HIV-positive. There was no significant difference in testing uptake in the two lottery groups (78%; P = 0.076) or two loss-framed groups (77%; P = 0.235) vs. two gain-framed groups (74%). Across incentive types, testing did not differ significantly in high-cost (76%) vs. low-cost (75%; P = 0.416) groups. Within low-cost groups, testing uptake was significantly higher in the lottery (80%) vs. gain-framed (72%; P = 0.009) group. CONCLUSION:Overall, neither offering incentives via lotteries nor framing incentives as losses resulted in significant increases in HIV testing compared with standard gain-framed incentives. However, when offering low-cost incentives to promote HIV testing, providing lottery-based rewards may be a better strategy than gain-framed incentives

Comparative effectiveness of novel nonmonetary incentives to promote HIV testing.

OBJECTIVE:To assess the comparative effectiveness of alternative incentive-based interventions to promote HIV testing among men. DESIGN:Randomized clinical trial. METHODS:We enumerated four Ugandan parishes and enrolled men at least 18 years. Participants were randomized to six groups that received incentives of varying type and amount for HIV testing at a 13-day community health campaign. Incentive types were: gain-framed (control): participants were told they would receive a prize for testing; loss-framed: participants were told they had won a prize, shown several prizes, asked to select one, then told they would lose the prize if they did not test; lotteries: those who tested had a chance to win larger prizes. Each incentive type had a low and high amount (∼US$1 and US$5/participant). The primary outcome was HIV-testing uptake at the community health campaign. RESULTS:Of 2532 participants, 1924 (76%) tested for HIV; 7.6% of those tested were HIV-positive. There was no significant difference in testing uptake in the two lottery groups (78%; P = 0.076) or two loss-framed groups (77%; P = 0.235) vs. two gain-framed groups (74%). Across incentive types, testing did not differ significantly in high-cost (76%) vs. low-cost (75%; P = 0.416) groups. Within low-cost groups, testing uptake was significantly higher in the lottery (80%) vs. gain-framed (72%; P = 0.009) group. CONCLUSION:Overall, neither offering incentives via lotteries nor framing incentives as losses resulted in significant increases in HIV testing compared with standard gain-framed incentives. However, when offering low-cost incentives to promote HIV testing, providing lottery-based rewards may be a better strategy than gain-framed incentives

Diagnosis of SARS‐CoV‐2 infection and COVID‐19:accuracy of signs and symptoms; molecular, antigen, and antibody tests; and routine laboratory markers

Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:. To assess the diagnostic accuracy of laboratory real-time polymerase chain reaction (RT-PCR) and other laboratory molecular tests to determine if a person presenting in the community or in secondary care has SARS-CoV-2 infection. To assess the diagnostic accuracy of each rapid PCR and antigen test to determine if a person presenting in the community or in secondary care has SARS-CoV-2 infection. To assess the diagnostic accuracy of each antibody test to determine if a person presenting in the community or in secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection. To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in the community, general practice, or at the emergency department has SARS-CoV-2 infection, COVID-19 pneumonia, or severe COVID-19 pneumonia/ARDS requiring hospital admission. To assess the diagnostic accuracy of routine laboratory testing to determine if a person has COVID-19 pneumonia or SARS-CoV-2 infection. Secondary objectives Where data are available, for reviews #1 to #5, we will investigate the accuracy (either by stratified analysis or meta-regression) according to: laboratory method, days of symptoms, severity of symptoms, reference standard, sample type, study design, setting; test brand and version, days of symptoms, severity of symptoms, reference standard, sample type, study design, setting; current infection or past infection, test brand and version, days of symptoms or days since symptoms resolved, reference standard, study design, setting; days of symptoms, reference standard, study design, setting; specific measurement or biomarker, days of symptoms, severity of symptoms, reference standard, sample type, study design, setting

Comparative effectiveness of novel nonmonetary incentives to promote HIV testing

10.1097/qad.0000000000001833AIDS32111443-145