North Carolina DHHS STAT Demonstration Project Protocol
HIV Prevention and Care Branch Version 1.0
CONFIDENTIAL DRAFT
June 28, 2002
STAT
SCREENING AND TRACING FOR ACTIVE HIV TRANSMISSION
A Collaborative Project of the University of North Carolina-Chapel Hill Center for AIDS Research and the North Carolina Department of Health and Human Services
Sponsored by:
University of North Carolina-Chapel Hill Center for AIDS Research
HIV/STD Prevention and Care Branch, Division of Public Health, North Carolina Department of Health and Human Services
Support Provided by:
bioMerieux
Beckman-Coulter, Inc
UNC-Chapel Hill Center for AIDS Research
The STAT Protocol Committee:
Protocol Chair: Christopher D. Pilcher, MD
Protocol Co-Chair: Peter A. Leone, MD
NC DHHS Representative: Evelyn Foust, MPH
UNC-CH CFAR Representative: Robert Ryder, MD
Project Manager: Trang Nguyen, MPH
Version 3.0
November 7, 2003
STAT PROTOCOL TEAM ROSTER
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North Carolina DHHS STAT Program Protocol
HIV Prevention and Care Branch Version 2.0
June 28, 2002
Protocol Chair
Christopher D. Pilcher, M.D.
Department of Medicine
CB 7030, 547 Burnett Womack Building
UNC-Chapel Hill
Chapel Hill, NC 27599-7030
Phone: (919) 966-2536
Fax: (919) 966-6714
Email:
Protocol Co-Chair
Peter Leone, MD
Department of Medicine
CB 7030, 547 Burnett-Womack Bldg
UNC-Chapel Hill
Chapel Hill, NC 27599-7030
Phone: (919) 966-2536
Fax: (919) 966-6714
Email:
NC DHHS Representative
Evelyn Foust, CPM, MPH
Division of Epidemiology
HIV/STD Prevention and Care
1902 Mail Service Center
PO Box 29601
Raleigh, NC 27699-1902
Phone: (919) 733-7301
Fax: (919) 733-1020
Email:
UNC CFAR Representative
Robert Ryder, MD
Department of Epidemiology
CB 7435, McGavran-Greenberg Hall
UNC-CH School of Public Health
Chapel Hill, NC 27599-7435
Phone: (919) 843-6182
Fax: (919) 966-2089
Email:
Project Manager
Trang Nguyen, MPH
Department of Epidemiology
CB 7435, McGavran-Greenberg
UNC-Chapel Hill School of Public Health
Chapel Hill, NC 27599-7435
Fax: (919): 966-2089
Email:
Social Epidemiologist
Adaora A. Adimora, MD
Department of Medicine
CB 7030, 547 Burnett-Womack Bldg
UNC-Chapel Hill
Chapel Hill, NC 27599-7030
Phone: (919) 966-2536
Fax: (919) 966-6714
Email: adimora @med.unc.edu
Senior Epidemiologist
William Miller, MD, PhD
Epidemiology, UNC-CH School of Public Health
Medicine, UNC-CH School of Medicine
CB 7435, 2105f McGavran-Greenberg Hl
Chapel Hill, NC 27599-7435
Phone: (919) 966-9407
Fax: (919) 966-2089
Email:
DHHS Policy & Special Projects Coordinator
Judy Owen-O’Dowd
Epidemiology & Communicable Diseases
N.C. Department of Health and Human
Services, Epidemiology Section
1902 Mail Service Center
Raleigh, NC 27699-1902
Phone: (919) 733-9553
Email: judy.owen-o'
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North Carolina DHHS STAT Program Protocol
HIV Prevention and Care Branch Version 2.0
June 28, 2002
NC DHHS Field Services Unit
Todd Vanhoy
Manager
585 Waughtown Street
Winston-Salem, NC 27107-2241
Phone: (336) 771-4641
Fax: (336) 771-4641
Email:
Rhonda M. Ashby
Assistant Manager
2045 C Eastgate Drive
Greenville, NC 27858
Phone: (252) 355-9084
Fax (252) 355-9095
Email:
NC DHHS Epidemiology and Special Studies
Delbert E. Williams, PhD
1902 Mail Service Center
Raleigh, NC 27699-1902
Phone: (919) 733-9606
Fax: (919) 715-7540
Email:
NC DHHS State Laboratory of Public Health
Lou Turner, DrPH
Director
1918 Mail Service Center
Raleigh, NC 27699-1918
Phone: (919) 807-8960
Fax: (919) 733-8695
Email:
J. Todd McPherson, MS
Virology/Serology Branch Head
306 North Wilmington Street
Raleigh, North Carolina 27601
Phone: (919) 733-7544
Fax: (919) 715-7700
Email:
Juanita Harris, MTASCP
Serology Unit Supervisor
306 North Wilmington St.
P.O. Box 306
Raleigh, N.C. 27611
Phone: (919) 733-7544
Fax: (919) 715-7700
Email:
Regina Lee
306 North Wilmington St.
P.O. Box 306
Raleigh, N.C. 27611
Phone: (919) 733-7544
Fax: (919) 715-7700
Email:
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North Carolina DHHS STAT Program Protocol
HIV Prevention and Care Branch Version 2.0
June 28, 2002
TABLE OF CONTENTS
Background
Public Health Significance …………………………………………………………….. / 7
Diagnostic Strategies in Current Use ………………………………………………… / 8
Rationale for STAT: Pilot Data ……………………………………………………….. / 8
The STAT Program …………………………………………………… / 11
NC DHHS Standard Operating Procedures Prior to Implementation of STAT
Outline ……………………………………………………………………………………. / 12
DIS Interview Format …………………………………………………………………… / 14
Revised NC DHHS Standard Operating Procedures to Implement STAT
STAT DIS Team ………………………………………………………………………… / 16
Protocol for Routine Testing and Notification ………………………………………... / 16
STAT Index Case Protocol …………………………………………………………….. / 20
STAT Partner Protocol …………………………………………………………………. / 23
Community Cases / 24
Referral to Care …………………………………… / 25
State Laboratory of Public Health Testing Procedures for STAT
Quality Assurance ………………………………………………………………………. / 27
Initial Screening for Acute and Chronic HIV Infection ………………………………. / 27
Confirming Possible Acute Infection ………………………………………………….. / 28
Blood Storage / 29
LSEIA Testing / 29
Patient Confidentiality and Risks …………………………………………………….
Consent …………………………………………………………………………………. / 31
Risk to Participants ……………………………………………………………………... / 31
Data Management and Related Confidentiality
Counseling and Testing Site Identification Number (CTS ID) ……………………… / 33
Partner ID ……………………………………………………………………………….. / 33
Identifiers and Access to Data ………………………………………………………… / 35
Data Processing ………………………………………………………………………… / 36
Evaluation ………………………………………………………………………………... / 39
References ……………………………………………………………………………….. / 51
Appendix A: HIV Testing Timetable………………………………………………..... / 53
Figures 1-3….……………………………………………………………………………. / 54-56
ACRONYMS
CTS Counseling and Testing Site
DIS Disease Intervention Specialists
EIA HIV Enzyme Immunoassay (aka ELISA Test)
ELISA HIV Enzyme-Linked Immunoassay
ESS Epidemiology and Special Studies Division of Department of Health and Human Services
NC DHHS North Carolina Department of Health and Human Services
STAT Screening and Tracing for Active HIV Transmission
STD MIS Sexually Transmitted Diseases Management Information System
UNC-CH CFAR University of North Carolina-Chapel Hill Center for AIDS Research
USPHS United States Public Health Service
WB Western Blot
Overview
The North Carolina DHHS HIV/STD Prevention and Care Branch’s Screening and Tracing for Active HIV Transmission (STAT) Program is an initiative to improve HIV prevention and care in NC through universal screening for acute HIV infection in NC’s routine HIV counseling and testing population, and through the rapid identification, notification and testing of sexual and needle-sharing partners of patients with acute HIV infection. The STAT Program procedures and evaluation plan detailed in this protocol will implement testing, outline data collection and management procedures and outline plans for evaluation. Goals of this evaluation process will be
· to measure the prevalence and clinical associations of acute HIV infection in primary care settings in North Carolina,
· to assess the identification of recent HIV transmitters in NC communities facilitated by the program,
· to assess the potential for targeting acute HIV screening to specific high risk groups of patients yet to be identified, and
· to assess the costs and benefits of implementing STAT testing and notification procedures as implemented over the course the program’s first 12 months.
The data collected during this initial evaluation period are expected to play a key role in shaping the future look of the program and informing policy recommendations regarding universal testing and notification of acute HIV infection both inside and outside of the state.
I. The NC DHHS Emphasis on Acute HIV Infection Diagnosis: Background
A. Public Health Significance. An estimated 40,000 new HIV infections occur annually in the US. Acute HIV infection—characterized by high virus burden and evolving host immunity—is sometimes accompanied by a self-limited, mononucleosis-like “acute retroviral syndrome” that is rarely diagnosed (Schacker 1996). It has been hypothesized that early antiretroviral treatment during this period may augment host immunity and improve long-term prognosis for treated patients (Rosenberg 2000). Moreover, HIV transmission can occur readily during acute HIV infection (Pilcher 2001) and may, in fact, account for a disproportionate amount of HIV transmission relative to transmission by individuals in later stages of infection (Jacquez 1994, Koopman 1997, Leynaert 1998). These observations agree well with mathematical models that predict elevated transmission probabilities due to higher shedding in semen during acute infection (Chakraborty 2001, Pilcher 2002), and with an increased probability of sexual transmission with increasing blood viral load (Quinn 2000a). Acute HIV infection is therefore an attractive target for public health interventions (Cates 1997, Janssen 2001). Because preliminary evidence suggests that early short-course antiretroviral treatment may alter long term prognosis in acute HIV infection (Rosenberg 2000, Oxenius 2000, Fidler 2001), current USPHS/DHHS guidelines for treatment of HIV infection recommend that urgent treatment be considered in the setting of acute infection. Other recommendations include obtaining HIV genetic sequencing (genotyping) to survey for drug resistance on all acutely infected patients in this country because of 1) the high prevalence of transmitted resistance to antiretrovirals in the treatment era, and 2) observations that transmitted resistant strains typically revert to “wild-type” within a few months of transmission without therapy. It should be noted that since there are no public health systems in place in the US for active acute infection surveillance, estimates on the prevalence of transmitted resistance are subject to significant reporting bias.
B. Diagnostic Strategies in Current Use. Assays used for HIV testing that are dependent on antibody detection will miss early acute infections unless they are used in conjunction with direct viral detection methods such as HIV RNA PCR or p24 antigen. A negative screening antibody test and a positive RNA or p24 test are required for real-time diagnosis. Seroconversion can occur as late as 6 months post exposure but the seronegative window using most modern HIV antibody tests is typically 3-10 weeks (Lindback 2000). Levels of viremia are detectable by HIV RNA PCR beginning about 1 week after infection (Busch 1997, Pilcher 2002), and become detectable by p24 antigen during week 2, just before the end of the pre-symptomatic incubation period (Schacker 1996, Pilcher 2001, Borrow 1997). Neither test has either low enough cost or adequate specificity to allow for widespread or routine screening. For these reasons, these tests are typically limited to use in patients with symptoms to suggest a high (>5%) pre-test probability of acute HIV infection (Hecht 2002). Since the symptoms of the acute retroviral syndrome are virtually indistinguishable from much more prevalent causes of infectious mononucleosis-like syndrome, the need for improved recognition of acute HIV infection is clear.
C. Rationale for STAT: Pilot Data. A UNC CFAR/NC DHHS pilot study examined the prevalence of acute HIV infection in the NC routine HIV counseling and testing population using HIV nucleic acid screening of seronegative serum specimens, analogous to HIV/hepatitis blood donor screening procedures (Pilcher 2002). This pilot study combined a pyramid-type specimen pooling scheme with ultra sensitive RNA PCR in a modification of a protocol first described by Quinn and colleagues (2000b) for incidence estimation purposes. By first screening for HIV RNA in pools made from seronegative specimens, and then deconstructing HIV RNA positive pools to determine individual positive specimens, it was possible to identify individuals that had possible acute HIV infection. HIV antibody negative/RNA positive patients were contacted by state Disease Intervention Specialists and confirmatory testing was performed. In the one-month initial pilot program, 8194 consecutive at risk subjects presenting for routine tests at 110 counseling and testing sites across NC were screened, of whom 39 were HIV antibody positive [chronic HIV infection prevalence: 47.6 per 10,000 at risk persons (95% CI 33.8-65.0 per 10,000)]. Of 8155 at risk subjects with negative antibody tests, 5 were HIV RNA positive, of whom 4 had true positive acute infection [prevalence 4.9 per 10,000 (95% CI 1.3- 12.5 per 10,000); because of pooling, overall specificity was excellent at 0.9999 (95% CI 0.9993-1.0000]. Interestingly, 3 of 4 acute infections were asymptomatic at initial testing but 2 subsequently developed a characteristic acute retroviral syndrome. In the project’s “continuation phase” (after the first week of testing), all results were completed within 14 days of testing. In total, 1 RNA test was necessary for each 55 specimens initially submitted to testing and additional testing costs were estimated at $2.01 per specimen tested or approximately $4,000 per additional case of HIV infection diagnosed. Manual pooling was laborious and required a full time technician to process 500 specimens per day.
These results suggest that antibody negative acute HIV infection may be unexpectedly prevalent and that routine screening for these infections is feasible. The STAT Program was therefore developed specifically to carry the concept forward and operationalize protocols for efficient acute HIV screening (using low cost, ultra-sensitive RNA detection technology and robotic pooling), rapid partner notification and screening in the public health setting. STAT protocols will be implemented on an ongoing basis with an initial summary evaluation scheduled after 12 months of data collection.
II. The STAT Program
A. Objective. The primary objective is to demonstrate feasibility and cost effectiveness of a statewide public health acute HIV infection screening program in a routine HIV testing and counseling population that uses automated pooling, low cost molecular testing and a system for sentinel surveillance and rapid response by disease intervention specialists.
B. Overview. The STAT Program will offer acute HIV screening to approximately 120,000 subjects annually beginning in fourth quarter of 2002. STAT procedures will encompass not only rapid testing, but will also include systems for surveillance and rapid response by NC DHHS Disease Intervention Specialists (DIS) in the event that acute infections or high risk sexual or drug use-related exposures are identified. The laboratory costs, DIS activity, project management and program evaluation are funded for the 12 months of the demonstration period through NC DHHS, UNC-CH Center for AIDS Research and industry sponsors.
C. Anticipated Results. The NC DHHS State Laboratory of Public Health will screen approximately 120,000 blood samples of all consecutive patients requesting routine HIV testing at North Carolina’s 110 voluntary counseling and testing centers during the 12 months preceding an initial summary STAT program evaluation. Based on pilot data, the STAT program expects to identify between 20 and 160 acute infections, and to identify 10-50 transmission pairs that will include one of these acutely infected individuals.
III. NC DHHS Standard Operating Procedures Prior to Implementation of STAT
A. Outline. The following HIV testing and notification procedures are standard prior to implementation of STAT. They will be substantially modified in order to fully implement STAT, as detailed in Section IV. (See Appendix A for HIV Testing Timetable.):
1. Pre-test Counseling: Patients who request an HIV test at one of the 110 NC voluntary counseling and testing sites are provided pre-test counseling regarding their HIV test. They are informed that: an HIV test consists of testing for HIV antibodies, they have a responsibility to inform sexual partners of a positive test result and the NC DHHS will inform or assist in notifying partners of a positive HIV test result. After patients sign a standard consent form for HIV testing, counselors complete a Counseling and Testing Site (CTS) form with the patient; the random identification number on this form (CTS ID) is used to anonymously identify the information recorded on the form and the blood samples sent to the State Laboratory of Public Health for HIV testing. Information collected on these forms includes demographic information, risk factors, testing site information, and reasons for seeking an HIV test. The CTS clinic maintains a log of the CTS ID and corresponding contact information. The State Laboratory, using the CTS form, can link a CTS ID with the site at which the patient was tested. Patients routinely schedule a follow-up appointment for two weeks later for result notification and are expected at the appointment regardless of the test result.