Universal Vs. Risk-Group Targeted HIV Screening in the ED
Universal Vs. Risk-Group Targeted HIV Screening in the ED
This single-center cluster-randomized trial compared the yield of universal and targeted screening for HIV in the ED, in the context of 2 concurrent seroprevalence studies. Seroprevalence estimates were obtained either by approaching patients consecutively (patient based) or from deidentified discarded blood samples, originally obtained for clinical purposes (remnant based).
The study enrolled patients from January 2008 through December 2010. Blocks of patients were randomized to be approached for HIV screening on a universal or targeted basis or, for the first 2 years of enrollment, in the patient-based seroprevalence study. The remnant-based seroprevalence study was conducted over the third year of the screening study. The study was approved by the institutional review board and overseen by a data and safety monitoring board. No harms or unintended study effects were recorded.
This study was conducted in the ED of a Midwestern, urban, 450-bed teaching hospital with 90,000 annual ED patient encounters. Of the ED patients, about 50% were black, 0.5% were Hispanic, and 40% were uninsured. Pediatric patients were rarely seen because a large pediatric ED is located nearby. A publicly funded HIV counseling and testing program has operated in this ED since 1998. The cumulative diagnosis rate of HIV/AIDS in the surrounding county is 229 per 100,000 persons.
For the screening arms, patients were ineligible if aged younger than 18 or older than 64 years, had known HIV infection, or previous approach for ED HIV testing that day. Postexposure testing (eg, occupational, assault) was not provided. For the seroprevalence arms, patients were ineligible if aged younger than 18 or older than 64 years.
Randomization Patients were approached for universal screening, targeted screening, or the patient-based seroprevalence estimate according to cluster randomization. Clusters were defined by combinations of four 6-hour periods spanning the full 24 hours and 4 separated ED patient care areas. The probability of each combination being a study period was set to achieve about 4 study periods per week. Study periods were then randomly assigned to being 1 of the 3 study arms.
Study periods were canceled without replacement if (1) the assigned ED area was closed during that time, (2) 2 study periods were adjacent in time and space, or (3) staffing was insufficient. Patients were allocated to periods based on their physical presence and not their time of arrival to the ED.
The screening study used the same procedures as the existing clinical screening program, but staffing was augmented to include every eligible patient. Additional study intervention was limited to randomizing patients between different selection criteria, both of which were used regularly by the program before the study.
HIV testing was offered at no cost with signed opt-in consent, detailed risk assessment, and formal prevention counseling. Ohio statutes and hospital policy mandated opt-in consent for HIV testing until 2011. There was no separate research consent; the clinical consent for HIV testing included IRB-approved language advising that information could be "analyzed to monitor the quality of the testing program and combined and reported to improve our understanding of issues related to the spread of HIV."
Services were provided by a cadre of 10 to 12 dedicated counselors operating in parallel with usual ED care. Counselors worked between 16 and 40 hours per week for about a year or more. They were trained in basic information regarding HIV illness, testing and transmission, formal prevention counseling, and ED and study operations. Training included 12 hours of didactic instruction, followed by 4 hours of role-play and observation or initial patient encounters. This was followed with periodic observation of counselor performance, feedback based on quality assurance review of data forms and enrollment logs, monthly meetings, and remediation if needed. Counselor work schedules were created entirely separately from activity randomization, so there would be no systematic difference in the way individual counselors were allocated between study arms. Risk assessment and counseling used a questionnaire-driven interview to promote an individualized plan for risk reduction. The questionnaire, recommendations, and HIV testing information were entered into the program's electronic record system.
Before October 2008, testing used conventional HIV enzyme-linked immunosorbent assay, with confirmatory Western blot. In 2008, testing switched to rapid assay (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test [OraSure Technologies, Bethlehem, PA] using oral fluid). If reactive, the patient underwent repeat rapid assay but with a whole-blood sample and also had blood drawn for confirmatory testing by Western blot. Negative results were reported to patients by telephone (conventional assay) or in person (rapid assay); positive results were provided in person.
Universal Arm Counselors approached every patient not known to meet exclusion criteria. The counselors could encourage participation by discussing the importance of testing generally but did not use individualized risk information to motivate testing.
Targeted Arm Counselors reviewed triage notations and electronic medical records to target patients or acted on staff referral. Indications for targeting contained over 50 items (see Appendix, Supplemental Digital Content, http://links.lww.com/QAI/A444), including (1) clinician identified signs and symptoms of HIV and (2) clinician or counselor identified risk behaviors, homelessness, mental illness, sexually transmitted disease exposure or infection, violence, substance use, pregnancy, and incarceration. Counselors did not systematically assess patients for every possible risk but were well familiar with criteria and approached patients whenever at least 1 risk was apparent. Patients for whom no risk was readily apparent were asked directly if they had (1) ever injected drugs, exchanged sex for drugs or money, had sex with a man (if male), or had sex with a partner with or at risk for HIV; or (2) in the past 2 years used cocaine or methamphetamine, had sex while using drugs or alcohol, been diagnosed with a sexually transmitted disease, or had more than 1 sex partner. Counselors could use risk information to encourage testing.
In all cases, counselors recorded the reasons prompting the test offer. Inability to complete the testing offer was counted as a failed approach, separate from declined offers. Counselors were necessarily unblinded, although separation of study arms was enforced through training, oversight, and color coding of study forms. Patients may have been aware of indications for testing but not that these varied systematically.
Patient-based Seroprevalence Study personnel consecutively approached every eligible patient to invite participation in a "study of diseases of public health importance." Patients received $10 for a blood sample and $5 for a health history. The consent process emphasized that data would be stripped of all identifiers before any analysis and disclosed HIV as 1 disease among others for which samples might be tested.
Remnant-Based Seroprevalence Discarded blood samples were obtained from the hospital laboratory for ED patients 1 week after receiving care during one of the seventeen 24-hour periods. Periods were purposively selected to provide data for 1 or 2 days each month and all days of the week. Research consent requirements were waived by the IRB.
Data Collection HIV counseling and testing data were extracted from screening program records. For the patient-based seroprevalence study, health questionnaires included information about HIV risk integrated within a broad health history. For the remnant-based seroprevalence estimate, trained abstractors conducted a structured chart review to collect analogous information. HIV status for both seroprevalence components was determined by a sequential method. If a clinical HIV test was performed and negative on or after the date of enrollment, the seroprevalence sample was presumed antibody negative without assay. Remaining samples were assayed in pools of 100-μL serum samples from 10 subjects, created from constituent pools of 5. Pools were tested for HIV antibodies by standard immunoassay [Abbott HIVAB HIV-1/HIV-2 (rDNA) EIA] and OraQuick ADVANCE Rapid HIV-1/2 Antibody Test. Individual positive samples were tested a second time and then confirmed by standard Western blot.
Outcomes The primary outcome was the proportion of new HIV diagnoses in the targeted and universal study arm. A positive HIV test was assumed to be a new diagnosis when there was no indication of previous HIV diagnosis from other sources such as the patient, medical record, other treatment providers, or health department.
Secondary outcomes included proportion of eligible and approachable ED patients who were tested and who were newly diagnosed, proportion offered testing who consented, risk profile of the tested patients, proportion tested who were notified, the number of positive patients linked to care, reasons for declining testing, and initial CD4 count of newly diagnosed patients. Seroprevalence estimates are provided to contextualize the screening comparison.
Comparison Between Screening Arms The proportion positive, or testing yield, was compared by estimating the difference between proportions and the 95% confidence interval of the differences. Secondary comparisons between groups used the χ test, Fisher exact test, or the Mann–Whitney U test. All statistical analyses were conducted using SPSS 20.0 (IBM Corporation, Armonk, NY). We did not adjust for clustering in our analysis; there was no reason to expect that patients within a cluster were more similar than patients in different clusters.
Individual patients often visit an ED more than once. We used encounters rather than patients as our primary unit of analysis. Because we have previously shown some differences in HIV screening program outcomes depending on unit of analysis, we conducted a secondary analysis to determine whether using only the first or the last test for patients with multiple encounters would influence the results.
Seroprevalence Estimation The patient-based and remnant-based seroprevalence studies were combined for analysis, although proportion positive was also calculated for each separately. Only the final enrollment was included in cases of duplicate enrollment. Patients were excluded from analysis if already diagnosed with HIV, either by self-report or medical record, or if HIV status could not be determined (eg, sample insufficient).
The positivity rate using targeted screening was expected to be approximately 1%. We selected 0.5% as the clinically important absolute difference in positivity that would be sufficient to influence program planning and design. A sample size of 2000 completed tests in each group was required for 80% power to detect a 2-sided 95% confidence interval for the difference in proportion positive to be ±0.5%. The study was stopped before reaching the enrollment goal because of exhausted resources.
Methods
Design Overview
This single-center cluster-randomized trial compared the yield of universal and targeted screening for HIV in the ED, in the context of 2 concurrent seroprevalence studies. Seroprevalence estimates were obtained either by approaching patients consecutively (patient based) or from deidentified discarded blood samples, originally obtained for clinical purposes (remnant based).
The study enrolled patients from January 2008 through December 2010. Blocks of patients were randomized to be approached for HIV screening on a universal or targeted basis or, for the first 2 years of enrollment, in the patient-based seroprevalence study. The remnant-based seroprevalence study was conducted over the third year of the screening study. The study was approved by the institutional review board and overseen by a data and safety monitoring board. No harms or unintended study effects were recorded.
Setting and Participants
This study was conducted in the ED of a Midwestern, urban, 450-bed teaching hospital with 90,000 annual ED patient encounters. Of the ED patients, about 50% were black, 0.5% were Hispanic, and 40% were uninsured. Pediatric patients were rarely seen because a large pediatric ED is located nearby. A publicly funded HIV counseling and testing program has operated in this ED since 1998. The cumulative diagnosis rate of HIV/AIDS in the surrounding county is 229 per 100,000 persons.
For the screening arms, patients were ineligible if aged younger than 18 or older than 64 years, had known HIV infection, or previous approach for ED HIV testing that day. Postexposure testing (eg, occupational, assault) was not provided. For the seroprevalence arms, patients were ineligible if aged younger than 18 or older than 64 years.
Randomization and Interventions
Randomization Patients were approached for universal screening, targeted screening, or the patient-based seroprevalence estimate according to cluster randomization. Clusters were defined by combinations of four 6-hour periods spanning the full 24 hours and 4 separated ED patient care areas. The probability of each combination being a study period was set to achieve about 4 study periods per week. Study periods were then randomly assigned to being 1 of the 3 study arms.
Study periods were canceled without replacement if (1) the assigned ED area was closed during that time, (2) 2 study periods were adjacent in time and space, or (3) staffing was insufficient. Patients were allocated to periods based on their physical presence and not their time of arrival to the ED.
ED HIV Counseling and Testing Program
The screening study used the same procedures as the existing clinical screening program, but staffing was augmented to include every eligible patient. Additional study intervention was limited to randomizing patients between different selection criteria, both of which were used regularly by the program before the study.
HIV testing was offered at no cost with signed opt-in consent, detailed risk assessment, and formal prevention counseling. Ohio statutes and hospital policy mandated opt-in consent for HIV testing until 2011. There was no separate research consent; the clinical consent for HIV testing included IRB-approved language advising that information could be "analyzed to monitor the quality of the testing program and combined and reported to improve our understanding of issues related to the spread of HIV."
Services were provided by a cadre of 10 to 12 dedicated counselors operating in parallel with usual ED care. Counselors worked between 16 and 40 hours per week for about a year or more. They were trained in basic information regarding HIV illness, testing and transmission, formal prevention counseling, and ED and study operations. Training included 12 hours of didactic instruction, followed by 4 hours of role-play and observation or initial patient encounters. This was followed with periodic observation of counselor performance, feedback based on quality assurance review of data forms and enrollment logs, monthly meetings, and remediation if needed. Counselor work schedules were created entirely separately from activity randomization, so there would be no systematic difference in the way individual counselors were allocated between study arms. Risk assessment and counseling used a questionnaire-driven interview to promote an individualized plan for risk reduction. The questionnaire, recommendations, and HIV testing information were entered into the program's electronic record system.
Before October 2008, testing used conventional HIV enzyme-linked immunosorbent assay, with confirmatory Western blot. In 2008, testing switched to rapid assay (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test [OraSure Technologies, Bethlehem, PA] using oral fluid). If reactive, the patient underwent repeat rapid assay but with a whole-blood sample and also had blood drawn for confirmatory testing by Western blot. Negative results were reported to patients by telephone (conventional assay) or in person (rapid assay); positive results were provided in person.
Selection and Recruitment for HIV Screening
Universal Arm Counselors approached every patient not known to meet exclusion criteria. The counselors could encourage participation by discussing the importance of testing generally but did not use individualized risk information to motivate testing.
Targeted Arm Counselors reviewed triage notations and electronic medical records to target patients or acted on staff referral. Indications for targeting contained over 50 items (see Appendix, Supplemental Digital Content, http://links.lww.com/QAI/A444), including (1) clinician identified signs and symptoms of HIV and (2) clinician or counselor identified risk behaviors, homelessness, mental illness, sexually transmitted disease exposure or infection, violence, substance use, pregnancy, and incarceration. Counselors did not systematically assess patients for every possible risk but were well familiar with criteria and approached patients whenever at least 1 risk was apparent. Patients for whom no risk was readily apparent were asked directly if they had (1) ever injected drugs, exchanged sex for drugs or money, had sex with a man (if male), or had sex with a partner with or at risk for HIV; or (2) in the past 2 years used cocaine or methamphetamine, had sex while using drugs or alcohol, been diagnosed with a sexually transmitted disease, or had more than 1 sex partner. Counselors could use risk information to encourage testing.
In all cases, counselors recorded the reasons prompting the test offer. Inability to complete the testing offer was counted as a failed approach, separate from declined offers. Counselors were necessarily unblinded, although separation of study arms was enforced through training, oversight, and color coding of study forms. Patients may have been aware of indications for testing but not that these varied systematically.
Recruitment for Seroprevalence Estimation
Patient-based Seroprevalence Study personnel consecutively approached every eligible patient to invite participation in a "study of diseases of public health importance." Patients received $10 for a blood sample and $5 for a health history. The consent process emphasized that data would be stripped of all identifiers before any analysis and disclosed HIV as 1 disease among others for which samples might be tested.
Remnant-Based Seroprevalence Discarded blood samples were obtained from the hospital laboratory for ED patients 1 week after receiving care during one of the seventeen 24-hour periods. Periods were purposively selected to provide data for 1 or 2 days each month and all days of the week. Research consent requirements were waived by the IRB.
Data Collection HIV counseling and testing data were extracted from screening program records. For the patient-based seroprevalence study, health questionnaires included information about HIV risk integrated within a broad health history. For the remnant-based seroprevalence estimate, trained abstractors conducted a structured chart review to collect analogous information. HIV status for both seroprevalence components was determined by a sequential method. If a clinical HIV test was performed and negative on or after the date of enrollment, the seroprevalence sample was presumed antibody negative without assay. Remaining samples were assayed in pools of 100-μL serum samples from 10 subjects, created from constituent pools of 5. Pools were tested for HIV antibodies by standard immunoassay [Abbott HIVAB HIV-1/HIV-2 (rDNA) EIA] and OraQuick ADVANCE Rapid HIV-1/2 Antibody Test. Individual positive samples were tested a second time and then confirmed by standard Western blot.
Outcomes The primary outcome was the proportion of new HIV diagnoses in the targeted and universal study arm. A positive HIV test was assumed to be a new diagnosis when there was no indication of previous HIV diagnosis from other sources such as the patient, medical record, other treatment providers, or health department.
Secondary outcomes included proportion of eligible and approachable ED patients who were tested and who were newly diagnosed, proportion offered testing who consented, risk profile of the tested patients, proportion tested who were notified, the number of positive patients linked to care, reasons for declining testing, and initial CD4 count of newly diagnosed patients. Seroprevalence estimates are provided to contextualize the screening comparison.
Statistical Analysis
Comparison Between Screening Arms The proportion positive, or testing yield, was compared by estimating the difference between proportions and the 95% confidence interval of the differences. Secondary comparisons between groups used the χ test, Fisher exact test, or the Mann–Whitney U test. All statistical analyses were conducted using SPSS 20.0 (IBM Corporation, Armonk, NY). We did not adjust for clustering in our analysis; there was no reason to expect that patients within a cluster were more similar than patients in different clusters.
Individual patients often visit an ED more than once. We used encounters rather than patients as our primary unit of analysis. Because we have previously shown some differences in HIV screening program outcomes depending on unit of analysis, we conducted a secondary analysis to determine whether using only the first or the last test for patients with multiple encounters would influence the results.
Seroprevalence Estimation The patient-based and remnant-based seroprevalence studies were combined for analysis, although proportion positive was also calculated for each separately. Only the final enrollment was included in cases of duplicate enrollment. Patients were excluded from analysis if already diagnosed with HIV, either by self-report or medical record, or if HIV status could not be determined (eg, sample insufficient).
Sample Size Considerations
The positivity rate using targeted screening was expected to be approximately 1%. We selected 0.5% as the clinically important absolute difference in positivity that would be sufficient to influence program planning and design. A sample size of 2000 completed tests in each group was required for 80% power to detect a 2-sided 95% confidence interval for the difference in proportion positive to be ±0.5%. The study was stopped before reaching the enrollment goal because of exhausted resources.
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