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Adult and Pediatric HIV/AIDS Confidential Case Reports
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Supplemental Surveillance Activity 2: Variant, Atypical, and Resistant
HIV Surveillance (VARHS) Technical Guidance
1
Technical Guidance for
HIV/AIDS Surveillance
Programs
Variant, Atypical, and Resistant HIV
Surveillance (VARHS)
HIV Incidence and Case Surveillance Branch
Atlanta, Georgia
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
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August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Contents — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Policies and Procedures for Variant, Atypical, and Resistant HIV Surveillance (VARHS) ...13-5
Background ............................................................................................................. 13-5
Objectives................................................................................................................ 13-6
Methods................................................................................................................... 13-7
Public Health Benefit ............................................................................................... 13-7
Structural Requirements.......................................................................................... 13-8
Policies and Procedures...................................................................................... 13-8
Laboratory Procedures...................................................................................... 13-10
Staffing Needs................................................................................................... 13-11
Process Standards ................................................................................................ 13-13
Determining Eligibility ........................................................................................ 13-14
Inclusion criteria ............................................................................................ 13-14
Exclusion criteria ........................................................................................... 13-14
Identifying Laboratories and Obtaining Remnant Specimens or Sequence Data..13-15
Specimen Handling and Transport Procedures ................................................ 13-16
Tube type for HIV diagnostic specimens....................................................... 13-16
Specimen handling........................................................................................ 13-16
Serum and plasma processing...................................................................... 13-16
Cryovials and aliquots ................................................................................... 13-17
Diagnostic and clinical testing and freezing of serum or plasma aliquots ..... 13-17
Specimen tracking data elements to be recorded in VARHS specimen log or
database ................................................................................................... 13-18
Shipment to the VARHS genotyping laboratory ............................................ 13-18
Required Data Elements ................................................................................... 13-19
Data used to determine VARHS eligibility..................................................... 13-19
Demographic and clinical data ...................................................................... 13-20
Specimen tracking data................................................................................. 13-20
Laboratory data ............................................................................................. 13-20
Returning Genotyping Results .......................................................................... 13-21
Ensuring Security and Confidentiality................................................................ 13-22
Data Management............................................................................................. 13-23
CDC software................................................................................................ 13-23
Identification of VARHS specimens .............................................................. 13-23
Data encryption and transfer......................................................................... 13-24
Data Analysis and Data Dissemination ............................................................. 13-25
Outcome Standards .............................................................................................. 13-25
References ............................................................................................................ 13-26
August 2007
Contents
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix A............................................................................................................ 13-29
Appendix B............................................................................................................ 13-30
Appendix C............................................................................................................ 13-31
Appendix D............................................................................................................ 13-32
Appendix E............................................................................................................ 13-33
Appendix E-1. Training and Certification for Shipping Infectious Substances .. 13-42
Appendix E-2. CDC VARHS Shipping Manifest................................................ 13-43
Appendix E-3. Stanford Laboratory’s Return of Shipping Container................. 13-44
Appendix F ............................................................................................................ 13-45
13-4
Contents
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Technical Guidance for HIV/AIDS Surveillance Programs —
Policies and Procedures for Variant, Atypical, and
Resistant HIV Surveillance (VARHS)
Background
The Centers for Disease Control and Prevention (CDC) is responsible for maintaining a
national surveillance system that provides data on the HIV/AIDS epidemic that can be
used for national, state, and local public health HIV/AIDS prevention program planning
and evaluation. Clinical and laboratory testing information is collected to characterize the
epidemic and guide public health action. HIV-1 genetic sequence data based on the pol
region (protease and reverse transcriptase genes) have been incorporated into the
HIV/AIDS surveillance system to evaluate the distribution of HIV-1 mutations associated
with HIV drug resistance and subtypes among persons with a new diagnosis of HIV
infection.
In the late 1990s, several new nucleoside reverse transcriptase inhibitors (NRTIs),
nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs)
were approved for treating HIV infection in the United States. These newer drugs, along
with the NRTIs already available, provide clinicians with a variety of choices for initiating
and changing antiretroviral treatment for patients infected with HIV-1. An international
panel with expertise in antiretroviral research and HIV patient care, convened by the
International AIDS Society–USA and an interagency work group of the Department of
Health and Human Services (DHHS) and the Public Health Service, provide
recommendations for prophylaxis or therapy that include all of the antiretroviral drugs
approved by the Food and Drug Administration (FDA) and in use in the United States (1).
The therapeutic purposes of antiretroviral drugs include prophylaxis after known
occupational exposure (postexposure prophylaxis), vertical transmission prophylaxis,
treatment of primary infection (4 to 7 weeks after infection), initial treatment from early
(little or no immunologic damage) to late (substantial immunologic damage) infection and
changes in treatment regimens depending on virologic and immunologic response (1–5).
Clinical trials are being conducted to evaluate the use of antiretroviral drugs for
preexposure prophylaxis. Studies have demonstrated that the results (genotype and
phenotype) of HIV drug-resistance testing can be used to predict clinical outcome and to
guide drug treatment choices (5). Also, studies have shown that the results of pol region
sequencing that indicate the presence of mutations associated with drug resistance predict
phenotypic sensitivity to antiretroviral drugs and clinical response (1, 5). Studies have also
demonstrated that the HIV-1 protease and reverse transcriptase genes of the pol region can
be used to characterize HIV-1 subtypes and that a high prevalence of HIV-1 subtypes
other than subtype B in a geographic area has implications for the appropriate selection of
HIV diagnostic and clinical tests for populations and individuals (6).
Given the public health concerns about primary HIV drug resistance, the clinical impact
on persons with a new diagnosis of HIV infection and the uncertain clinical significance
of resistant HIV strains, CDC funded a project called Antiretroviral Drug Sentinel
Surveillance to Examine Trends in Prevalence of Drug-Resistant Strains of HIV in 2002.
August 2007
Background
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
This demonstration project showed that it was feasible to use remnant sera for genotyping;
in turn, this led to the inception of variant, atypical, and resistant HIV-1 surveillance
(VARHS).
On June 25, 2004, VARHS received a non-research determination from the CDC Human
Subjects Office (Appendix A). The document that serves as the basis for the federal
regulations for protecting human research participants (Title 45 of the Code of Federal
Regulations part 46, 45 CFR 46) is available at http://www.hhs.gov/ohrp/humansubjects/
guidance/45cfr46.htm). Subpart A, subsection 46.101c states that “the [federal]
Department or Agency heads retain final judgment as to whether a particular activity is
covered by this policy.” The policy refers to the requirements for human subjects
protection review for research protocols under the 45 CFR 46 regulations. Disease
surveillance is one of the 4 major public health practice activities that usually involve data
collection but are not, according to 45 CFR 46, research and thus do not need review by an
institutional review board (IRB). Although CDC determined that VARHS is a disease
surveillance activity by CDC (IRB review not required), this determination does not
supersede state or local laws or regulations that may require IRB notification or review for
public health surveillance activities.
On July 1, 2004, VARHS was incorporated nationally into routine HIV surveillance, and
22 surveillance areas were funded to participate in VARHS (Appendix B).
Objectives
The primary objectives of VARHS are to
1.
2.
13-6
Incorporate surveillance of transmitted strains of variant, atypical, and resistant
HIV-1 into routine HIV surveillance activities by
•
amplifying and sequencing the pol region (protease and reverse
transcriptase genes) from persons with a new diagnosis of HIV infection
who have been reported to the HIV/AIDS Reporting System (HARS)
•
estimating the prevalence of mutations associated with HIV drug
resistance, resistant patterns, and trends in dissemination of drug-resistant
strains
•
determining the prevalence of genetic subtypes to gain insight into the
genetic diversity of strains and distribution of B and non-B variants among
populations
Provide data on HIV-1 drug resistance, subtypes, and factors associated with
resistance to assist HIV treatment, prevention, and program planning and
evaluation
Objectives
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Methods
VARHS is used to evaluate the prevalence of HIV-1 drug resistance and the distribution
of HIV-1 subtypes among persons with a new diagnosis who have been reported to HARS
by state, county, or city departments of health. Specimens from these persons should be
included by using either of 2 methods.
First, if sufficient volume is available, aliquots of remnant diagnostic specimens should be
set aside for HIV-1 drug-resistance testing from each blood specimen drawn for HIV
testing from eligible persons in participating areas. For persons meeting VARHS criteria,
HIV genetic sequencing (i.e., genotyping) will be performed on the protease and reverse
transcriptase genes to detect the presence of mutations associated with HIV-1 drug
resistance. HIV-1 subtypes will also be identified on the basis of these genes.
HIV-1 drug-resistance testing for VARHS is performed with standard tests, which are
widely used clinically. Like drug-resistance testing in other infectious disease surveillance
systems (e.g., tuberculosis, urinary tract infections, and sexually transmitted diseases),
testing diagnostic specimens for HIV-1 drug resistance and HIV-1 subtype surveillance is
not experimental and does not require informed consent (7–9). Areas may choose to
include information in their HIV testing forms to inform persons that HIV drug-resistance
testing is part of HIV diagnostic testing in participating areas. For persons with a new
diagnosis who have been reported and whose specimens are successfully amplified and
genotyped through the VARHS system, the health department will provide a hard copy of
the results to the health care provider(s) designated by the persons tested.
Second, if private-sector laboratories performed genotyping on specimens from persons
eligible for inclusion in VARHS, surveillance areas should request electronic sequence
data from the laboratories.
Genotyping results and information from the HIV surveillance case report will be used to
estimate the prevalence of HIV-1 drug resistance and the distribution of HIV-1 subtypes
among persons with a new diagnosis who have been reported as having HIV infection.
Prevalence will also be estimated for relevant demographic groups and HIV transmission
categories. HIV sequence information may also be used to track the spread and clustering
of atypical HIV strains that are of interest nationally.
Public Health Benefit
Although previous surveys have been based on convenience samples of specimens,
VARHS is the first surveillance system in the United States designed to evaluate all
persons who have been given a diagnosis of HIV infection and reported to HARS/eHARS
from participating areas. VARHS will determine the distribution of drug-resistant strains
and subtypes among persons with a new diagnosis who have been reported as having
HIV-1, thus supporting efforts to characterize and track the HIV epidemic nationally.
VARHS will also provide information on trends in the transmission of drug-resistant
strains and the factors associated with resistance. Analyses will support evaluation of first-
August 2007
Methods
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
line antiretroviral drugs and provide information that will be useful in developing new
antiretroviral drugs. Strategies for using specific prophylactic drugs will be enhanced by
information from the surveillance of HIV drug resistance.
VARHS will support evaluation of the usefulness of testing baseline clinical HIV-1 drug
resistance in specific geographic areas. Current DHHS guidelines for the treatment of
HIV-1 infection recommend baseline resistance testing for all HIV patients before the
initiation of antiretroviral therapy. Even when therapy is deferred, the guidelines suggest
that baseline testing should be considered: “In the absence of therapy, resistant viruses
may decline over time to less than the detection limit of standard resistance tests but may
still increase the risk of treatment failure when therapy is eventually initiated” (1). The
DHHS guidelines cite a 2005 cost-effectiveness analysis that concluded, “A strategy of
genotype-resistance testing at initial diagnosis of HIV infection increased per-person
quality-adjusted life expectancy by 1.0 months, with an incremental cost-effectiveness
ratio of $23,900 per quality-adjusted life-year gained, compared with no genotype testing.
The cost-effectiveness ratio for resistance testing remained less than $50,000 per qualityadjusted life-year gained, unless the prevalence of resistance was <1%, a level lower than
those reported in most regions of the United States and Europe…. Genotype-resistance
testing of chronically HIV-infected, antiretroviral-naive patients is likely to improve
clinical outcomes and is cost-effective…. Resistance testing at the time of diagnosis
should be the standard of care” (10).
VARHS will also provide public health and clinical personnel with information on the
distribution of HIV-1 subtypes in the United States over time. If the prevalence of HIV-1
non-B subtypes increases, this finding could have implications for vaccine studies. Also,
should specific drug-resistant mutations be associated with some non-B subtypes, there
could be implications for treatment guidelines.
In the surveillance of other organisms, such as Mycobacterium tuberculosis, molecular
surveillance has allowed identification of atypical strains of special interest (9, 11).
Although no such HIV strains have been identified, routine surveillance based on
sequencing and phylogenetic analyses of the HIV pol region will allow such strains to be
detected. Routine surveillance will also provide information on multidrug-resistant strains
in various geographic areas and specific population subgroups. HIV-1 genetic sequencing
surveillance data collected over time will also contribute to analyses of the evolution of
HIV-1 in the United States.
Structural Requirements
Policies and Procedures
All persons with a new diagnosis of HIV infection after confidential testing should be
reported to HARS in accordance with Technical Guidance for HIV/AIDS Surveillance
Programs, Vol. I: Policies and Procedures (12). VARHS is an extension of the national
population-based HIV/AIDS case surveillance system, and state and local health
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Structural Requirements
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
department partners and CDC will use the case surveillance infrastructure to collect the
information necessary to estimate the prevalence of transmitted HIV-1 drug resistance and
HIV-1 subtypes.
VARHS will be implemented in areas that also conduct HIV incidence surveillance. CDC
recommends that HIV incidence surveillance procedures be in place before VARHS
implementation is planned. In some circumstances, however, the simultaneous
implementation of both surveillance systems may be beneficial. Before implementing
VARHS, surveillance areas must
•
Consult their CDC HIV incidence surveillance epidemiologist and the CDC
VARHS project officer or coordinator about the appropriate time to plan and
implement VARHS
•
Develop VARHS guidance outlining local policies and procedures, which must be
reviewed and approved by CDC
•
Host a site visit by CDC
•
Document CDC approval before collecting specimens for VARHS
Because VARHS is an integrated component of HIV/AIDS surveillance, documentation
of VARHS activities should be incorporated into locally tailored policy and procedures
manuals developed for HIV/AIDS surveillance (12) to establish standardization, maintain
continuity of meaning, document changes over time, and develop training programs. In
addition to the information in Technical Guidance for HIV/AIDS Surveillance Programs,
Vol. I: Policies and Procedures (12), VARHS-specific policies and procedures should
include information related to
•
Responsibilities of staff
•
Training in VARHS procedures for health care providers, counselors, and other
staff at participating testing sites and clinics
•
Identification of participating laboratories
•
Eligibility determination
•
Specimen handling and transport procedures
•
Collection of VARHS-specific specimen tracking and laboratory data elements
•
Entering and importing data into the Incidence and Viral Resistance (IVR)
database
•
Data management practices
•
Return of genotyping results
•
Monthly data transmission to CDC
•
Security and confidentiality
•
Local analysis and dissemination plan
•
Expansion plan (including a timeline for jurisdiction-wide implementation of
VARHS)
August 2007
Structural Requirements
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
At the end of some sections in this document, a box (similar to the one headed Sample
VARHS Implementation Task) is used to present task-specific guidance that the
surveillance area will need to address in order to implement VARHS. The local VARHS
guidance should include a description of local plans and policies and procedures related to
each task, as the completion of these tasks is key in the successful implementation of
VARHS.
Sample VARHS Implementation Task
VARHS areas should complete each implementation task that appears at
the end of selected sections in this document.
Laboratory Procedures
Specimen handling and transport procedures are stringent for VARHS, because proper
specimen handling and transport contribute to the rate of successful amplification for
genetic sequencing. Specimen handling and transport procedures should be decided by the
public health laboratory and local sites. If necessary, procedures can be modified when
new aspects of the surveillance system are instituted. At a minimum, surveillance areas
planning to implement VARHS need to take the following laboratory procedures into
consideration.
13-10
•
If volume seems sufficient for the purposes of all basic laboratory tests and other
local priorities, such as archiving and HIV incidence surveillance, a 1 mL
(optimal) aliquot from all enzyme immunoassay (EIA)–reactive specimens should
be frozen at –70ºC as soon as possible after the first reactive EIA.
•
The following will maximize chances for successful amplification for genetic
sequencing
Plasma and serum should be separated as quickly as possible, and neither
should be refrigerated until after separation.
HIV diagnostic testing or other relevant clinical testing should begin
immediately after separation of plasma or serum.
Sera or plasma should be kept on the bench at room temperature for as short a
time as possible before being returned to the refrigerator or placed on ice.
Once frozen, specimens for genotyping should not be thawed until they reach
the genotyping laboratory. A freeze-thaw cycle will reduce the chance of
successful amplification for genotyping.
Specimens should be shipped on dry ice to the genotyping laboratory.
•
A system must be in place to collect all required data elements for specimen
tracking and to transmit them to CDC (see Appendix F).
Structural Requirements
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Staffing Needs
Implementation of VARHS requires personnel with specific skills and dedicated time to
effectively integrate VARHS into the core HIV/AIDS surveillance system. In general,
personnel who work primarily on core HIV/AIDS surveillance or HIV incidence
surveillance will develop work plans to integrate VARHS into HIV/AIDS surveillance.
VARHS staff should have
•
An understanding of VARHS and the characteristics of the local HIV/AIDS
surveillance system, including HIV incidence surveillance
•
An understanding of how HIV diagnostic laboratories function and how they are
related to the public health system
•
Good communication skills
•
Strong leadership skills
•
An ability to work closely with CDC, other states, local HIV diagnostic and
clinical sites, private providers, and laboratories
CDC recommends a full-time VARHS coordinator position dedicated to implementing
and maintaining the system. The number of other personnel assigned to VARHS may
vary, depending on the implementation phase, prevalence of HIV/AIDS, and available
resources.
VARHS coordinator
•
Provide overall management of VARHS
Develop local VARHS guidance (to be reviewed and approved by CDC)
Serve as the lead for area-specific implementation of the VARHS technical
guidance
Serve as the primary CDC contact for VARHS
Manage employee or other service contracts related to VARHS
•
Develop training materials and courses, including presentations for local clinical
and diagnostic sites and laboratories to introduce VARHS
•
Train providers, counselors, and other staff at participating clinical and diagnostic
sites
•
Oversee data collection processes
Directly manage or oversee the process for determining the eligibility of
specimens for VARHS
Work with the genotyping laboratory to develop procedures for shipment of
specimens and receipt of genotyping results
Develop and manage the system for returning genotyping results to designated
providers
•
Collaborate with other VARHS staff
•
Participate in CDC site visits, trainings, and workshops
August 2007
Structural Requirements
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Epidemiologist
•
Plan and implement the integration of VARHS activities into HIV core
surveillance and HIV incidence surveillance activities
•
Develop a VARHS analysis plan
•
Develop systems to ensure data quality, analyze local VARHS data, and produce
reports
•
Participate in data dissemination activities
Collaborate with stakeholders to determine data needs and frequency of
reporting
Identify results and surveillance issues for review and dissemination
Develop a data dissemination plan in collaboration with the VARHS
coordinator and CDC
•
Participate in CDC site visits, trainings, and workshops
Laboratory liaison
•
Serve as the liaison between the public health department and laboratories from
which specimens are being shipped
•
Oversee transfer of specimen tracking data from laboratories to the IVR database
at the health department
•
In collaboration with liaisons based at participating laboratories, develop local
procedures for processing and shipping specimens to the genotyping laboratory
•
In collaboration with liaisons based at participating laboratories, develop quality
control procedures for preparing specimens
•
Develop and oversee procedures to maintain security and confidentiality of
specimen identifiers and results
•
Participate in CDC site visits, trainings, and workshops
Laboratory liaison based at a participating HIV diagnostic laboratory
•
Work with the VARHS coordinator and the health department laboratory liaison to
develop the laboratory-specific plan for processing, storing, determining
eligibility, tracking, and shipping specimens to the genotyping laboratory
•
Oversee preparation and shipping of VARHS specimens to the genotyping
laboratory
•
Monitor quality control procedures for preparing VARHS specimens
•
Record specimen tracking data in the log or database
Data manager
13-12
•
Assist the VARHS coordinator with daily management of VARHS data
•
Serve as subject matter expert on VARHS data elements and data management
programs
Structural Requirements
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
•
Receive data from other health department entities and the genotyping laboratory,
and incorporate those data into the IVR database and data sets for transfer to CDC
•
Assess data quality
•
Obtain a Secure Data Network (SDN) certificate and renew the certificate annually
to allow for data transmission to CDC
•
Identify at least 1 backup person to hold an SDN certificate and maintain the list of
persons with certification, notifying CDC of changes
•
Oversee VARHS data management
Assess data collection methods
Modify CDC’s generic data management programs for use at the local level
Maintain the IVR database
Run SAS statistical software programs to produce monthly data sets
Develop and implement edit checks and edit data
Collaborate with the VARHS coordinator, epidemiologist, and other area
surveillance and prevention staff on data editing, data entry, and data set
preparation
Prepare monthly data set for transmission to CDC
Transfer data through SDN to CDC
Prepare data sets for local analysis
Collaborate with CDC on data set preparation for national resistance estimates
Prepare HIV resistance data reports for local use in collaboration with the
VARHS coordinator, epidemiologist, and CDC
•
Maintain security and confidentiality of data
•
Participate in CDC site visits, trainings, and workshops
VARHS Implementation Task
Areas should identify the staff needed to implement VARHS and define
staff roles, responsibilities, and the time each staff member should spend
on VARHS.
Process Standards
VARHS involves the following processes:
•
Determining eligibility
•
Identifying laboratories and obtaining remnant specimens or sequence data
•
Developing specimen handling and transport procedures
•
Collecting required data elements
August 2007
Process Standards
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
•
Returning genotyping results
•
Ensuring security and confidentiality
•
Managing data
•
Analyzing and disseminating data
Determining Eligibility
Specimens confirmed as HIV-1–positive by Western blot or other methods acceptable to
the department of health are potentially eligible for VARHS. All specimens yielding
indeterminate or negative Western blot results in the absence of other proof of HIV
infection should be handled according to standard laboratory procedures for handling,
storage, and discarding specimens.
The VARHS coordinator will identify the confirmed positive frozen aliquots that are eligible
for VARHS by matching laboratory and HARS data (or data from an equivalent HIV/AIDS
reporting system). The VARHS coordinator also will identify cases with electronic sequence
data that are eligible for VARHS. Eligibility should be established according to the following
inclusion and exclusion criteria at the case and the specimen level.
Inclusion criteria
•
The specimen is the diagnostic specimen (the HIV-1–positive specimen that led to
the case report to HARS).
•
If the diagnostic specimen is unavailable, a later specimen is eligible provided that
the later specimen was drawn <3 months after the date of the diagnostic
specimen and
the later specimen was drawn for an HIV-related test (viral load, polymerase
chain reaction, CD4 count).
•
Electronic sequence data are eligible if the specimen used for genotyping was
drawn <3 months after the date of the diagnostic specimen.
Exclusion criteria
13-14
•
The specimen is not from the diagnostic specimen that led to the report to HARS.
•
The specimen is from an HIV-related test (viral load, polymerase chain reaction,
CD4 count) or a genotyping test and was drawn >3 months after the date of the
diagnostic specimen.
•
The person had received antiretroviral drugs before the VARHS specimen was
collected.
•
There is no method to link the person to HARS (i.e., the person was tested
anonymously).
•
An earlier specimen had been sequenced and documented in VARHS.
•
The person’s diagnosis was HIV-2 infection.
•
The specimen was collected before the surveillance area implemented VARHS.
Process Standards
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
How often HARS is checked for eligibility is left to the discretion of the surveillance area;
however, at a minimum, HARS should be checked to determine VARHS eligibility
•
before sending specimens for genotyping and
•
before each monthly data transfer to CDC.
All specimens that are not eligible for VARHS should be handled according to local
standard laboratory procedures.
Identifying Laboratories and Obtaining Remnant Specimens or Sequence
Data
In each surveillance area, laboratories that could participate in VARHS will be identified
from a review of local HIV surveillance data and laboratory licensing records. In practice,
VARHS will usually begin in public health laboratories, which collaborate closely with
the health department.
The preferred default practice for VARHS is to have eligible specimens shipped by the
central public health laboratory to the CDC-contracted genotyping laboratory for VARHS
testing. Deviations should be discussed with CDC. Shipping costs associated with sending
specimens from state public health laboratories to the genotyping laboratory should be
paid from the funds provided through CDC’s cooperative agreement with each
participating area. Surveillance areas are responsible for including estimated shipping
costs in their request for funds and for budgeting accordingly.
To minimize the possibility that a person with a new diagnosis might begin taking
antiretroviral drugs before a specimen is collected, HIV genetic sequencing for VARHS
must be performed on an HIV-1–positive specimen collected at the time of HIV diagnosis
or at the time of a specimen collected at a follow-up visit no more than 3 months after
diagnosis. If volume and logistics permit, a remnant specimen for VARHS will be
obtained from all eligible, confirmed HIV-positive diagnostic specimens. Specimen types
suitable for VARHS are serum, plasma, and whole blood.
The use of dried fluid spots for VARHS is being evaluated as an alternative type of
specimen collection but has not been approved for use in VARHS.
National commercial reference laboratories and private laboratories where HIV diagnostic
or clinical testing is performed can also participate in VARHS, if resources are available,
to allow remnant specimens to be processed within the time frames described in the
following sections or to allow time for the receipt of genotyping results (i.e., sequence
data). Reimbursements to local commercial and private laboratories will be determined,
on the basis of local policies, by each surveillance area.
When sequence data are available from commercial or private laboratories for cases that
are eligible for VARHS, the following should be done:
•
Secure the fasta files (standard text-based format for representing nucleic acid
sequences) containing the nucleotide sequence.
•
Match the sequence data with case information in the IVR database.
•
Indicate in the appropriate field in the IVR database that the specimen was handled
through a commercial or private laboratory.
August 2007
Process Standards
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
VARHS Implementation Task
Identify laboratories that are required to report HIV-positive test results,
the total number of new diagnoses made annually in each laboratory, and
the number of HIV-positive specimens suitable for VARHS (plasma,
serum, or whole blood).
Specimen Handling and Transport Procedures
Specimen handling and transport procedures should be decided by the public health
laboratory and local sites. If necessary, procedures can be modified when new aspects of
the surveillance system are instituted. The following sections describe tube types,
transport times, and processing times that are optimal for VARHS. Before implementing
VARHS, surveillance areas should take these factors into consideration when developing
local procedures.
In general, 1 or more central public health laboratories will process and ship VARHS
specimens to the genotyping laboratory. (See Appendix E for detailed shipping procedures
for serum and plasma specimens.)
Tube type for HIV diagnostic specimens
The decision on the type of tube to use for HIV diagnostic and follow-up blood draws
should be made on the basis of local diagnostic and surveillance needs and available
resources. If changes in practice are being considered, note that the HIV diagnostic or
the follow-up blood draw should be 8 to 10 mL to ensure sufficient volume for
additional HIV surveillance uses, including VARHS.
Specimen handling
After the blood draw and before serum or plasma separation, the tube should be stored
at room temperature. The blood draw and specimen transport should be timed so that
specimens arrive at the HIV testing laboratory and are processed (separated, aliquoted,
and frozen) within 96 hours or as soon as possible after the blood draw. The likelihood
of amplification may be reduced when specimen processing takes longer.
Serum and plasma processing
For HIV testing and VARHS, it is recommended that specimens be centrifuged to
remove red blood cells and prevent hemolysis. Successful HIV amplification for
sequencing is less likely with hemolyzed specimens. After separation of the serum or
plasma, specimens should be maintained in a refrigerator at 4ºC or kept on ice until the
specimens are EIA tested and eligible aliquots are frozen for potential use in VARHS.
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Process Standards
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Cryovials and aliquots
Cryovials for sera or plasma aliquoted for VARHS should be 2 mL, polypropylene,
with screw caps and external threads. If labels are not used, the tube should have a
writing area.
After the VARHS identification number (VARHS ID) is generated locally, each
specimen should be labeled with the appropriate VARHS ID, by either writing the ID
number on the tube with a permanent marker or attaching a label to the tube. Labels
that adhere to frozen tubes can be supplied at no cost by CDC upon request.
Ideally, an aliquot of 1 mL per specimen should be prepared for HIV genetic
sequencing and sent to the genotyping laboratory. When volume is limited, priority is
given to (1) the laboratory’s standard operating procedures for HIV diagnostic and
clinical testing and serum archiving, (2) HIV incidence surveillance activities, and (3)
VARHS. If less than 1 mL is available for genetic sequencing when all other needs
have been met, the specimen may still be sent for sequencing after consultation with
the genotyping laboratory.
Diagnostic and clinical testing and freezing of serum or plasma aliquots
The following will maximize chances for successful amplification for genetic
sequencing.
•
HIV diagnostic testing or other relevant clinical testing should begin immediately
after separation of plasma or serum.
•
Sera or plasma should be kept on the bench at room temperature for as short a time
as possible before being returned to the refrigerator or placed on ice.
•
If volume appears sufficient for the purposes of all basic laboratory tests and other
local priorities, such as archiving and HIV incidence surveillance, a 1 mL aliquot
from all EIA-reactive specimens should be frozen at –70ºC as soon as possible
after the first reactive EIA.
Note: Optimally, the specimen should be frozen at –70ºC within 96 hours after
the blood draw. After 96 hours, the likelihood of amplification may be
reduced, but the specimens should still be sent for genetic sequencing
provided that amplification results are followed up carefully.
•
Once frozen, specimens for genotyping should not be thawed until they reach the
genotyping laboratory. A freeze-thaw cycle will reduce the chance of successful
amplification for genotyping.
After the first reactive EIA, the aliquot is still considered an HIV diagnostic specimen;
it will not be defined as a VARHS specimen until it has been confirmed as HIVpositive and until it is clear that specimen needs for all higher priority laboratory tests,
including diagnostic HIV testing and HIV incidence testing, have been fulfilled.
Aliquots frozen as potential VARHS specimens can be thawed at any time if they are
needed for higher priority tests. The freeze-thaw cycle will not affect the HIV
diagnostic test results or STARHS (serologic testing algorithm for recent HIV
seroconversion) results for HIV incidence testing.
August 2007
Process Standards
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Specimen tracking data elements to be recorded in VARHS specimen log
or database
VARHS data are considered part of routine HIV surveillance data and should be held
to the standards of security and confidentiality for HIV/AIDS surveillance outlined in
Technical Guidance for HIV/AIDS Surveillance Programs, Vol. III: Security and
Confidentiality Guidelines (13). The diagnostic testing laboratory should maintain a
VARHS specimen tracking log or database to provide information for evaluation if
problems with amplification, specimen mixup, or specimen contamination occur. (See
Table 2, Appendix F, for a list of the minimum required data elements for specimen
tracking.) The specimen tracking data elements listed in Table 3 are optional unless
the amplification rates for a particular surveillance area or local site are low (<90%). If
the rates are low, all of the specimen tracking data elements listed in Table 3, in
addition to those in Table 2, will be required. A Microsoft Access database for
storage of the required specimen tracking and laboratory data is supplied by CDC.
Specimen tracking and laboratory data may be recorded first on person laboratory
slips or specimen labels. Batch slips may be used for the initial recording of
information applicable to batches of specimens, such as site of the blood draw, lists of
patient identification numbers for specimens transported in a batch, date/time of
receipt in the diagnostic laboratory, range of laboratory accession numbers for a batch,
date/time of centrifugation, date/time of separation, date/time of first positive EIA
result, date/time of aliquoting, and date/time aliquots were frozen. All or some of this
information may also be captured from in-house laboratory databases. Information
will be transferred to the IVR database for each specimen that is confirmed as HIVpositive and not identified as ineligible. Laboratory or health department personnel
may work with CDC to develop methods of information transfer to minimize duplicate
recording of information.
Shipment to the VARHS genotyping laboratory
Shipments should be made to the genotyping laboratory at least monthly. The
frequency of shipments per month should be determined locally: the goal is to return
resistance test results to designated health care providers as soon as possible. (For
handling, packaging, and shipping of specimens, see Appendix E.)
Surveillance staff will compile a list of VARHS–eligible specimens to be packaged
and shipped by the state or local public health laboratory to the genotyping laboratory.
VARHS ID numbers should be recorded on the specimen manifest included in the
shipment. Two additional copies of the specimen manifest should be made: 1 should
be sent to sent to CDC by the US Postal Service or through SDN; the other should be
filed with the VARHS coordinator (see Appendix E).
13-18
Process Standards
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
VARHS Implementation Task
VARHS areas should identify all laboratories that will transport specimens
to a central public health laboratory, which will ship specimens to the
genotyping laboratory. The local version of this guidance should include
descriptions of the procedures by which the VARHS coordinator will
receive monthly information about specimen tracking, receive shipping
manifests whenever shipments are made, and communicate at least
quarterly with laboratories making the shipments.
VARHS areas should include detailed laboratory procedures in the local
version of this guidance (e.g., information on obtaining and processing
specimens, determining eligibility, recording specimen tracking data for
local use, storing specimens, and shipping specimens). All procedures
should be developed by the VARHS coordinator in consultation with
participating laboratories.
Required Data Elements
VARHS data are considered part of routine HIV surveillance data and should be held to
the security and confidentiality standards for HIV/AIDS surveillance outlined in
Technical Guidance for HIV/AIDS Surveillance Programs, Vol. III: Security and
Confidentiality Guidelines (13).
Data used to determine VARHS eligibility
HARS or equivalent HIV/AIDS reporting systems will serve as the primary means of
determining eligibility by using the date of the first positive HIV test result.
Information on the prior use of antiretroviral drugs may be obtained from the
incidence surveillance Testing and Treatment History Data or other sources, provided
that information is collected on whether antiretroviral drugs have ever been used (i.e.,
no time limit should be placed on the history of antiretroviral drug use).
The elements of specimen tracking and laboratory data are linked with the HIV
surveillance database to determine whether the person was reported to HARS more
than 3 months before the relevant blood draw. Given the commitment to make reports
available to providers in “real time,” the shipment of specimens for VARHS should
not be delayed more than 30 days for the purposes of such evaluation (if possible,
specimens should be shipped within 6 weeks after the HIV diagnostic test or other
blood draw).
The dates of HIV diagnosis and the prescription of antiretroviral drugs may not be
available in HIV/AIDS surveillance reports until after VARHS specimens have been
shipped, tested, and entered in the IVR database. If additional data makes a case
ineligible, the reason for ineligibility should be recorded in the database.
August 2007
Process Standards
13-19
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Demographic and clinical data
VARHS does not require the collection of additional demographic or clinical data.
Instead, relevant data are supplied by HARS or the local equivalent. (See Table 1 of
Appendix F for the minimum set of data elements required for determining HIV-1
drug resistance and HIV-1 subtype prevalence in the population and in population
subgroups.) Demographic data used to estimate the prevalence of HIV-1 drug
resistance may include age, sex, race/ethnicity, country of origin, and transmission
categories associated with HIV infection. These elements will contribute to the
calculation of prevalence estimates for national subgroups; local prevalence may be
estimated in areas where the number of cases is sufficient.
Specimen tracking data
The required data elements for specimen tracking (i.e., must be collected for every
specimen) are listed in Table 2 of Appendix F, and the optional data elements for
specimen tracking are listed in Table 3 of Appendix F.
Note: CDC will analyze amplification rates stratified by surveillance area. If the
amplification rates in a surveillance area are low (<90%), all the data
elements for specimen tracking listed in Tables 2 and 3 will be required.
These additional data must be collected until the amplification problem has
been resolved or until CDC concludes that the problem is not associated with
the procedures for handling or storing specimens.
Laboratory data
Data transmitted to CDC must not include personal identifiers and must be encrypted
and password protected as specified in Technical Guidance for HIV/AIDS
Surveillance Programs, Vol. III: Security and Confidentiality Guidelines (13).
For specimens sent to the CDC contract and state laboratories, the genotyping
laboratory will do the following:
13-20
Transmit information on amplification to the health department and to CDC
Transmit the complete sequence of the protease gene and at least the first 240
codons of the reverse transcriptase gene, both as nucleotides and amino acids
Transmit a separate list of all mutations (including those associated with drug
resistance and those not associated with drug resistance) of any strain that
differs from the reference strain used at the laboratory
Provide hard copy of laboratory reports (to the appropriate health department
only)
Process Standards
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
VARHS Implementation Task
VARHS areas should review Appendix F and determine the completeness
and quality of the data elements used for analysis in VARHS. Because all
of the demographic and clinical data elements used are key elements for
general HIV surveillance, areas may wish to explore methods for
increasing the reporting of these elements (e.g., some areas have added
specific elements, such as country of birth, to their counseling and testing
laboratory request forms).
Returning Genotyping Results
HIV genetic sequencing is usually performed for clinical purposes for persons receiving
treatment for HIV. Physicians who treat HIV-infected persons are familiar with the
formats in which results are reported. The genotyping laboratory sends the hard copy of a
report (similar to the reports of drug-resistance testing, with which physicians are familiar)
to the health department no more than 30 days after the genotyping laboratory receives the
specimen. Because the interpretation of these results requires familiarity and training, the
health department should not return genotyping results directly to the patient, but to the
patient’s designated health care provider.
A person with HIV-1–positive results who returns for posttest counseling or follow-up
should
•
Receive a brief explanation of ancillary HIV diagnostic testing, including
genotyping
•
Receive instruction on how to designate a health care provider to receive, at that
time or later, the genotyping result if the patient wishes to do so
•
Receive a brief explanation on when the health department will send the results to
the health care provider
The health department is responsible for
•
Determining the method(s) by which the patient can designate a health care
provider(s) who will receive the genotyping result
•
Developing a method for the health care provider to obtain the genotyping results
•
Sending the hard copy of reports to the health care provider of the patient’s
choosing
•
Acting as a repository for the hard copy of reports for a locally specified time
If the blood draw that produced a VARHS specimen was performed at a clinical site to
which a patient is returning for medical consultation or care, the health department may
arrange for the genotyping report to be returned directly to the patient’s provider at that
clinical site.
August 2007
Process Standards
13-21
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
VARHS Implementation Task
Before VARHS is implemented, staff should determine the method(s) by
which the patient can designate a health care provider(s) who will receive
the genotyping results. Methods should be put in place to allow the patient
to designate a health care provider(s) at the time of the initial diagnosis or
later.
Ensuring Security and Confidentiality
HIV testing is a medical procedure. Therefore, policies and procedures are in place to
protect the confidentiality of tested persons and their medical records. VARHS will be
performed only on specimens that have tested positive for HIV or specimens used for the
follow-up of a confirmed HIV-positive result.
VARHS data are considered part of routine HIV surveillance data and should be held to
the standards of security and confidentiality for HIV/AIDS surveillance outlined in
Technical Guidance for HIV/AIDS Surveillance Programs, Vol. III: Security and
Confidentiality Guidelines (13). Current policies and procedures, based on these
guidelines and local laws, are used by state and local health departments to secure hard
copy and electronic information to protect the confidentiality of persons reported as
having HIV infection. These measures must be extended to protect VARHS data held
locally. Access by VARHS staff to information in HARS, HIV incidence surveillance
data, and VARHS data is governed by the same security and confidentiality requirements.
All staff responsible for the transmission and receipt of specimen shipping manifests,
VARHS sequence data, or reports of results must be trained in the security and
confidentiality procedures for HIV/AIDS surveillance.
Information that could identify a person (e.g., name, Social Security number, full date of
birth, address, ZIP code) will not be included in data sets transmitted from local
surveillance areas to CDC. Data transmitted to CDC must be encrypted and password
protected according to Technical Guidance for HIV/AIDS Surveillance Programs, Vol.
III: Security and Confidentiality Guidelines (13).
13-22
Process Standards
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
VARHS Implementation Task
VARHS areas should review their security and confidentiality
requirements and if necessary, draft specific procedures for handling
VARHS data or add VARHS components to the local protocol. VARHS
areas should also review their protocol and outline how VARHS data will
be stored and secured. Personnel with access to the data should receive
annual training in security and confidentiality procedures and should sign a
confidentiality statement that outlines the procedures and the consequences
of violating them.
Data Management
All data will be considered part of routine HIV surveillance data. Data entry and
management will take place at state or local health departments by the use of HARS or
eHARS and software developed by CDC or software that is compatible with CDC
software.
CDC software
The IVR database supplied by CDC is a Microsoft Access database, an adjunct to
HARS and eHARS, with tables for specimen tracking and HIV drug-resistance data.
An additional table is provided for local data entry and for use by local HIV
surveillance staff for the purposes of determining eligibility or for returning results.
CDC also provides a SAS program that facilitates the merging of specimen tracking
and drug-resistance data (from the IVR database) with selected demographic and
clinical data (from HARS or eHARS). The SAS program produces a data quality
report along with a cumulative SAS data set to be submitted to CDC.
Identification of VARHS specimens
A VARHS ID will be assigned to each specimen sent for genotyping and used for
importing HIV genetic sequencing information to the IVR database. The 14 digits of
the VARHS ID are assigned as follows:
August 2007
Digits 1–4: These 4 digits represent the Federal Information Processing
Standard (FIPS) code of the surveillance area.
Digits 5–8: These 4 digits represent the site where the blood draw was
performed.
Digits 9–10: These 2 digits identify the last 2 digits of the year the blood was
drawn.
Digits 11–14: These 4 digits are a sequence assigned by the health department.
Process Standards
13-23
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
The IVR database includes functions to allow areas to enter their FIPS code only once
and to create a menu of blood drawing sites and their codes. The VARHS ID will be
created automatically in the IVR database when the 4 components listed above are
entered for each specimen.
All data from the health department, local laboratories, genotyping laboratory, and
HARS or an equivalent reporting system will be associated with either a VARHS ID
number or a HARS State No. and then will be merged on the basis of these IDs. In
addition to the VARHS ID, a specimen accession number may be entered in the
database for local use.
Data encryption and transfer
Data transmitted to CDC must not include personal identifiers and must be encrypted
and sent through SDN, as specified in Technical Guidance for HIV/AIDS Surveillance
Programs, Vol. III: Security and Confidentiality Guidelines (13). Either SEAL or
Pretty Good Privacy (PGP) encryption software must be used to encrypt all data being
sent through SDN (13). SEAL software, for encrypting data sent to CDC, is provided
by CDC at no cost. VARHS surveillance areas must purchase PGP software with at
least 128-bit encryption to encrypt communications with genotyping laboratories. The
PGP Personal Desktop edition is suitable; a perpetual license is recommended. All
persons using PGP to encrypt and decrypt data must exchange PGP encryption keys.
Any encryption software other than SEAL or PGP must be approved by CDC.
Electronic data sent from the genotyping laboratory to VARHS areas must be
encrypted with PGP (or equivalent software). Please note that to receive genetic
sequencing data from the CDC contract laboratory, VARHS areas must purchase PGP
encryption software. The genotyping laboratory and the VARHS area must exchange
PGP encryption keys.
CDC will use PGP software to encrypt quality assurance data and will send those data
to VARHS areas through SDN (13).
Before the 15th day of each month, the complete VARHS data set from the preceding
month should be transmitted to CDC.
VARHS Implementation Task
The local guidance should include the procedure for entering specimen
tracking, genotyping, and local data into the VARHS database, exporting
these data from the VARHS database, and using SAS to merge these data
with selected demographic and clinical variables from HARS. Before
transmitting the monthly VARHS data set to CDC, VARHS staff must
have encryption software and a CDC-approved SDN certificate and must
understand CDC’s security and confidentiality guidelines (13). If PGP is
used, all persons who encrypt and decrypt data must exchange encryption
keys.
13-24
Process Standards
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Data Analysis and Data Dissemination
To standardize the national resistance data set, CDC uses a regularly updated program to
analyze resistance data transmitted from the genotyping laboratories. This program
translates the nucleotide sequence and incorporates information on individual mutations
of interest, the level of resistance to each antiretroviral drug in common use, and HIV-1
subtype.
The prevalence of resistance to at least 1 antiretroviral drug and the distribution of HIV-1
subtypes among persons with a new diagnosis of HIV infection should be reported
annually at the national and local levels. The prevalence of resistance to individual
antiretroviral drugs and categories of commonly used antiretroviral drugs (currently
NRTIs, NNRTIs, and PIs) may also be reported. These data will be stratified by
demographic factors or transmission category for subpopulation analyses at the national
and local levels. If adequate case counts are available, stratification will allow
comparisons of differing geographic areas and of differing transmission categories.
Aggregate data from the participating surveillance areas will be analyzed by CDC, and
results will be disseminated. Each surveillance area will be responsible for conducting
analyses at the local level.
As appropriate, results will be presented at conferences and published in peer-reviewed
journals. The authors representing the surveillance areas and those representing CDC will
be determined for each presentation or paper.
VARHS Implementation Task
VARHS areas should describe, in the local version of the VARHS
guidance, the proposed plan for analyzing and disseminating VARHS data.
Outcome Standards
Outcome standards described in the Introduction to Policies and Procedures and Data
Quality sections of Technical Guidance for HIV/AIDS Surveillance Programs, Vol. I:
Policies and Procedures (12) should be applied to VARHS. Given the time-sensitive
nature of VARHS data elements, meeting the core surveillance standards for case
ascertainment and timeliness is essential to the success of VARHS. The quality of the HIV
resistance estimate depends on the quality of data in the VARHS system. All outcome
standards for VARHS relate only to cases in persons who resided in the surveillance area
at the time of diagnosis.
•
The minimum standard for collecting the required specimen tracking and
laboratory data elements is 85% (goal, 100%).
•
Each year, for at least 50% of the persons in a jurisdiction who have a new
diagnosis and have been reported to HARS, a specimen should be sent for
genotyping and documentation in the IVR database (50% of cases diagnosed in a
year should have genotyping results 12 months after the diagnosis year).
August 2007
Outcome Standards
13-25
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
References
1.
DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines
for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
October 10, 2006. Available at http://www.aidsinfo.nih.gov/ContentFiles/
AdultandAdolescentGL.pdf. Accessed April 12, 2007.
2.
Centers for Disease Control and Prevention. US Public Health Service Task Force
recommendations for use of antiretroviral drugs in pregnant HIV-1–infected
women for maternal health and interventions to reduce perinatal HIV-1
transmission in the United States. MMWR 2002;51(RR-18):1–38.
3.
Centers for Disease Control and Prevention. Updated U.S. Public Health Service
guidelines for the management of occupational exposures to HBV, HCV, and
HIV and recommendations for postexposure prophylaxis. MMWR 2001;50(RR11):1–42.
4.
Centers for Disease Control and Prevention. Antiretroviral postexposure
prophylaxis after sexual, injection-drug-use, or other nonoccupational exposure to
HIV in the United States. MMWR 2005;54(RR-2):1–19.
5.
Hirsch MS, Brun-Vezinet F, Clotet B, et al. Antiretroviral drug resistance testing
in adults infected with human immunodeficiency virus type 1: 2003
recommendations of an International AIDS Society–USA panel. Clin Infect Dis
2003;37:113–128.
6.
Bennett DE. HIV genetic diversity surveillance. J Infect Dis 2005;192:4–9.
7.
Interagency Task Force on Antimicrobial Resistance. A public health action plan
to combat antimicrobial resistance, part 1: domestic issues. Available at
http://www.cdc.gov/drugresistance/actionplan/. Accessed July 10, 2007.
8.
Centers for Disease Control and Prevention. Reported Tuberculosis in the United
States, 2005. Atlanta, Ga: US Department of Health and Human Services; 2006.
Available at http://www.cdc.gov/tb/surv/surv2005/. Accessed July 16, 2007.
9.
Lewis B, Granich R, Courval J, et al. Epidemiology of multi-drug-resistant
Mycobacterium tuberculosis in the United States, 1996–2000. Annual meeting of
the American Public Health Association; November 2003; San Francisco,
California. Abstract 105.
10. Sax PE, Islam R, Walensky RP, et al. Should resistance testing be performed for
treatment-naïve HIV-infected patients? a cost-effectiveness analysis. Clin Infect
Dis 2005;41:1316–1323.
11. Munsiff SS, Nivin B, Sacajiu G, Mathema B, Bifani P, Kreiswirth BN.
Persistence of a highly resistant strain of tuberculosis in New York City during
1990–1999. J Infect Dis 2003;188;356–363.
13-26
References
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
12. Centers for Disease Control and Prevention and Council of State and Territorial
Epidemiologists. Technical guidance for HIV/AIDS surveillance programs, vol 1:
policies and procedures. 2005. Available at https://team.cdc.gov/team/cdc/
dispatch.cgi/w.nchstp_dhap_hicsb/tart/hicsb_TechGuid/.frame [passwordprotected Web site].
13. Centers for Disease Control and Prevention and Council of State and Territorial
Epidemiologists. Technical guidance for HIV/AIDS surveillance programs, vol 3:
security and confidentiality guidelines. 2006. Available at http://www.cdc.gov/
hiv/topics/surveillance/resources/guidelines/guidance/. Accessed July 10, 2007.
August 2007
References
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Notes
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August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix A
National Center for HIV, STD, and TB Prevention’s Non-research
Determination for HIV Variant, Atypical, and Resistant HIV-1 Surveillance
August 2007
Appendix A
13-29
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix B
Participating Surveillance Areas
The following surveillance areas were funded to participate in VARHS (including sites
that participated in the antiretroviral drug resistance testing [ARVDRT] evaluation
project) as of 2004.
1.
Chicago Department of Public Health
2.
Colorado Department of Public Health and Environment
3.
District of Columbia Department of Health
4.
Florida Department of Health
5.
Illinois Department of Public Health
6.
Indiana State Department of Health
7.
Louisiana Office of Public Health
8.
Maryland Department of Health and Mental Hygiene
9.
Massachusetts Department of Public Health
10. Michigan Department of Community Health
11. Mississippi State Department of Health
12. New Jersey Department of Health and Senior Services
13. New York City Department of Health and Mental Hygiene
14. New York State Department of Health
15. North Carolina Department of Health
16. Pennsylvania Department of Health
17. Puerto Rico Department of Health
18. Seattle and King County Public Health
19. South Carolina Department of Health
20. Texas Department of State Health Services
21. Virginia Department of Health
22. Washington State Department of Health
13-30
Appendix B
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix C
Epidemiologic Flowchart for Variant, Atypical, and Resistant HIV-1
Surveillance
†
See technical guidance section on determining eligibility.
* If sequences are received from commercial laboratories, Dept. of Health should determine eligibility.
August 2007
Appendix C
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Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix D
Laboratory Flowchart for Variant, Atypical, and Resistant HIV-1 Surveillance
†
13-32
See technical guidance section on determining eligibility.
Appendix D
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix E
Technical Guidance for the Processing, Storage, and Shipment of Variant,
Atypical, and Resistant HIV-1 Surveillance (VARHS) Specimens to
Genotyping Laboratories for Antiretroviral Drug-Resistance Testing
Purpose
This technical guidance describes the methods for the processing, storage, and shipment
of VARHS serum and plasma specimens that will be tested for HIV antiretroviral drug
resistance and HIV-1 subtyping.
Introduction
Serum or plasma from HIV diagnostic specimens should be collected and frozen at –70ºC.
For the purpose of resistance testing, serum should ideally be separated within 48 hours
after the blood draw and frozen within 96 hours after the blood draw. Frozen serum or
plasma will be shipped to a CDC-designated testing laboratory for genotypic analysis.
Note: Surveillance areas may elect to store a backup aliquot for use in the event that
something happens to the original aliquot sent to the laboratory or if a specimen
needs to be retested for any reason.
Setting and Personnel Required for Specimen Processing
•
Centrifugation, aliquoting, and shipping should be performed at or under the
auspices of a laboratory that has been certified by CLIA (Clinical Laboratory
Improvement Amendments of 1998) to handle HIV-positive specimens.
Note: All personnel handling specimens should receive training in handling
bloodborne pathogens. (See OSHA’s [Occupational Safety and Health
Administration’s] standards regarding occupational exposure to
bloodborne pathogens at http://www.osha.gov/pls/oshaweb/
owadisp.show_document?p_table=STANDARDS&p_id=10051.)
•
Personnel handling or processing specimens should receive training in the relevant
laboratory techniques for handling HIV-positive specimens and for performing the
specific tasks required.
•
The setting in which centrifugation, aliquoting, and shipping are done should meet
Biosafety Level 2 specifications, required by the US Department of Health and
Human Services, for the handling of HIV specimens (http://www.cdc.gov/od/ohs/
biosfty/bmbl4/bmbl4s2.htm).
Materials
The following materials are required for the collection and shipment of VARHS
specimens:
•
Cryogenic vials: 1.5 to 2 mL, with screw cap, external threads, O-ring, and made
of polypropylene.
August 2007
Appendix E
13-33
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
•
Freezer labels that will remain on the tubes upon freezing. Many cryogenic vials
bear a label area that is suitable for writing with a permanent marker. Writing on
the printed area, instead of affixing a label, is acceptable.
•
Cardboard storage boxes for cryogenic vials: 81 spaces per box.
•
Low temperature freezer: –70ºC.
Keep a daily temperature log to ensure that the freezer is operating properly.
House the freezer in a location with proper ventilation to avoid overheating
and freezer failure.
Be sure that the –70ºC freezer has enough space for the storage of VARHS
specimens.
•
A supply of dry ice in pellet form.
•
Saf-T-Pak (http://www.saftpak.com) STP 320 insulated shipping containers
certified for frozen diagnostic specimens (i.e., certified for HIV-positive
specimens and dry ice).
•
Courier’s airbills.
•
Materials for packing the shipping container (see 2.4).
Specimen Collection and Processing
13-34
1.
All processing of specimens should be done by personnel qualified to handle
HIV-positive specimens under the auspices of a laboratory equipped to handle
HIV-positive specimens (http://www.cdc.gov/od/ohs/biosfty/bmbl4/
bmbl4s2.htm).
2.
If the amount of serum seems to be sufficient for all diagnostic needs and HIV
incidence testing, transfer an aliquot from the collection tube to the corresponding
vial for HIV drug-resistance testing as soon as possible after separation (1 mL per
cryogenic vial is optimal).
3.
Ship the aliquot to the Stanford University laboratory or to the locally contracted
genotyping laboratory. Surveillance areas may elect to store a backup aliquot for
use in the event that something happens to the original aliquot sent to the
laboratory or if a specimen needs to be retested for any reason.
4.
Place the aliquots in cardboard boxes for cryogenic vials in a –70ºC freezer.
Optimally, freeze the aliquot within 96 hours after the blood draw.
5.
The aliquots frozen as potential specimens for HIV drug-resistance testing remain
HIV diagnostic specimens until all HIV diagnostic tests and any other basic
laboratory tests have been completed. If additional serum is needed for diagnostic
testing or HIV incidence testing, the aliquot for potential HIV drug-resistance
testing should be thawed and used for those purposes. If a backup specimen was
stored, the backup specimen should be used first. If more volume is required, the
specimen designated for the genotyping laboratory may also be used.
Appendix E
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
6.
After a positive result from an HIV confirmatory test or at the time determined by
standard laboratory procedures, label each cryogenic vial with the appropriate
VARHS specimen ID. The VARHS ID is a 14-digit number that is assigned to
each specimen sent for genotyping.
The 14-digit VARHS specimen ID consists of the following:
7.
The 4 digits that denote the surveillance area (digits 1–4), which
correspond to the Federal Information Processing Standard (FIPS) code for
the surveillance area (state or city)
The 4-digit site number (digits 5–8), which designates where the blood
draw was performed
The last 2 digits of the year of the blood draw (digits 9–10)
The 4-digit sequence number (digits 11–14), which is assigned by the
local health department
Every specimen that is eligible for VARHS should be entered into a specimen
handling and processing log or a database. Each surveillance area is expected to
develop its own log or database or to use the Microsoft Access database provided
by CDC. In addition, each surveillance area is responsible for ensuring that all
information for each specimen is logged before the specimen is shipped.
Shipping
1. Preliminary procedures for shipping to the Stanford University
genotyping laboratory (CDC contract laboratory)
1.1.
Specimens for genotypic resistance testing should be sent to the Stanford
University laboratory. All specimens should be shipped as diagnostic
specimens, according to International Air Transport Association (IATA)
Packing Instruction 650. Dry ice should be included with each shipment, as
specified in IATA Packing Instruction 904.
1.2.
Because shipping specimens involves using dry ice, shipping personnel
must be trained and certified to ship dangerous goods. (See Appendix E-1
for a list of companies that provide training.)
1.3.
Establish contact with the point person at the Stanford University
laboratory.
•
•
•
•
August 2007
Stanford Virology Main Lab: 650-498-5575
Stanford HIV Genotyping Laboratory: 650-725-7165
Christina Trevino: 650-725-7165
Mary Arroyo: 650-725-4146
Appendix E
13-35
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
1.4.
A “test” shipment must be sent before the first shipment of VARHS
specimens to ensure that all procedures are in place. The test shipment
should exactly duplicate a real shipment (i.e., ship frozen liquid in
cryogenic vials on dry ice) and should be sent only once. (See the
procedures outlined in 1.5–1.8.)
The purpose of the test shipment is to familiarize the sender with the
processes for notifying the laboratory about the shipment and for packing
and shipping the diagnostic specimens on dry ice. Shipping frozen water on
dry ice without the infectious substance labels will accomplish the purpose
of the test shipment.
1.5.
Arrange for the preparation of the test shipment and the initial shipment to
be overseen by laboratory staff experienced in the shipment of comparable
specimens.
1.6.
Notify the Stanford University laboratory that the test shipment is on the
way by calling the main laboratory at 650-725-7165 or by e-mailing (do
not e-mail or fax the shipping manifest).
In the call or e-mail, include the number of specimens being shipped and if
applicable, the FedEx tracking number. Per CDC’s Technical Guidance for
HIV/AIDS Surveillance Programs, Vol. III: Security and Confidentiality
Guidelines (13), do not e-mail or fax the shipping manifest (the manifest is
included in the shipment).
1.7.
Be sure to have an adequate number of STP 320 shipping containers or the
equivalent are on hand. The Stanford laboratory will return these
containers to the shipping laboratory (they are expensive and should be
reused).
1.8.
Be sure to have an adequate supply of the courier’s airbills on hand.
2. Packing procedures for shipping to the Stanford University
laboratory
13-36
2.1.
Specimens must be shipped on the same day that they are packed. Plan to
begin the packing process early so that the container(s) will be ready for
the courier’s last pick-up of the day. Pack and ship only Monday through
Wednesday. Never pack and ship the week of Thanksgiving, Christmas,
New Year’s, or July Fourth.
2.2.
Personnel in the shipping laboratory should read and walk through all of
these steps before starting to prepare the actual shipment in order to be
familiar with the requirements.
2.3.
Wear gloves and a lab coat.
Appendix E
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
2.4.
Bring the STP 320 shipping container and other packing materials into the
area where the shipment is being prepared. Check to be sure that the
container includes the following items:
•
•
•
•
•
•
2 sheets of bubble wrap
2 STP 710 2-part secondary pressure vessels or equivalent certified
containers
Two 250 mL absorbent strips
Class 9 label and label for the quantity of dry ice
Other hazard and handling labels
1 instruction sheet
2.5.
For a diagram of the contents of the shipping container, see the Saf-T-Pak
catalog (http://www.saftpak.com). Of the listed contents, use only what is
needed for each shipment. Save leftover supplies for future shipments.
2.6.
If the STP 320 shipping container is being reused, the labels will already be
in place on the outer cardboard container.
2.7.
Be sure that adequate supplies of the other materials listed in 2.4 are on hand.
2.8.
Prepare 3 copies of the shipping manifest (Appendix E-2). On the manifest,
write the VARHS ID number on each vial to be shipped, along with the
date the specimen was drawn and the date the specimen was frozen (freeze
date).
Note: The freeze date entered here should be the last freeze date for the
aliquot being shipped.
Indicate (circle) whether the specimens are serum or plasma, and record the
volume being shipped if it is less than 1 mL. Bring the copies of the
manifest into the area where the shipment is being prepared.
•
•
•
2.9.
Copy 1 of the shipping manifest should be included in the shipment to
the Stanford laboratory.
Copy 2 of the shipping manifest should be sent to CDC (see 3.2). Send
through SDN (preferred) or the US Postal Service.
Copy 3 of the shipping manifest should be kept by the surveillance
area’s VARHS coordinator or the laboratory sending the specimens to
the Stanford laboratory.
Prepare the courier’s airbill (Appendix E-3); Stanford will use the airbill to
return the shipping container for reuse. On the airbill, fill in the shipping
laboratory’s complete return address, Stanford University’s address, and
the billing number. Staple the airbill to the shipping box return form. Bring
the copy of the airbill into the area in which the shipment is being prepared.
2.10. If dry ice is in another location, which requires leaving the area where the
shipment is being prepared, put the dry ice needed for this shipment in a
separate container and bring it to the shipping area.
August 2007
Appendix E
13-37
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
2.11. Go to the freezer and remove the entire 2-inch freezer box containing the
specimens to be sent.
2.12. Bring the specimens to the area where the shipment is being prepared.
Specimens are to remain frozen at all times and therefore should not be
removed from a –70°C environment for more than a few minutes.
2.13. Recheck the screw-cap lids on the specimen vials and tighten if necessary.
2.14. Place the freezer box containing the specimens in the secondary pressure
vessel (leak-proof) and make sure the specimens are surrounded by bubble
wrap and absorbent strips. The vials should not move around or rattle
inside the vessel.
2.15. Place the secondary pressure vessel in the inner box and place the inner
box in the polystyrene cooler.
2.16. Do not put dry ice inside the inner box.
2.17. Pack pelleted dry ice in the shipping container and around the inner box.
The STP 320 shipping container will hold ~8 kg of dry ice (~10 lbs); if the
cooler is packed completely, this quantity of dry ice will keep the contents
frozen for more than 80 hours.
2.18. Place the lid on the polystyrene cooler.
2.19. Fold 1 copy of the VARHS shipping manifest in half and place it on top of
the shipping box return form with the airbill that Stanford laboratory will
use to return the shipping container to the shipping laboratory (for reuse),
and place on top of the polystyrene lid.
2.20. Fold over the top flaps of the outer box and seal with clear shipping tape.
2.21. Place the category B label (“UN 3373”) over the 2½'' × 2½'' diamondshaped outline on the outer box.
2.22. Write “Diagnostic Specimens” on the outer box, adjacent to the category B
label.
2.23. Place the Class 9 hazard label over the 4'' × 4'' diamond-shaped outline.
2.24. Place the label for the net quantity of dry ice over the rectangular outline
adjacent to the Class 9 hazard label. On the label, write the approximate
amount (in kg) of dry ice used to pack the container.
Note: The labels (category B designation, Class 9 hazard, and quantity of
dry ice) can be purchased.
2.25. Prepare the courier’s paperwork as directed by the training and
certification course and select the overnight shipping option.
2.26. If the preceding steps are not completed before the courier’s last pickup of
the day, unpack the specimens and put them back in the –70ºC freezer and
begin the process again on the next appropriate day.
13-38
Appendix E
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
3. Procedures for shipping to the Stanford University laboratory
3.1.
Ship only Monday through Wednesday. Never ship the week of
Thanksgiving, Christmas, New Year’s, July Fourth, or major local
holidays.
3.2.
Send the second copy of the shipping manifest to the CDC Laboratory
Liaison, Richard Kline, through the SDN (preferred) or the US Postal
Service. On the manifest, indicate the date that the specimens were shipped
to the Stanford laboratory. Do not e-mail or fax the shipping manifest to
CDC or to the Stanford laboratory.
Mailing Address:
Attn: Richard Kline
Centers for Disease Control and Prevention
1600 Clifton Rd, NE, MS E-47
Atlanta, GA 30333
Phone: 404-639-4958
3.3.
Keep the third copy of the shipping manifest.
3.4.
Notify the Stanford laboratory that a shipment is on the way by calling the
HIV genotyping laboratory at 650-725-7165 or by e-mailing (do not e-mail
or fax the shipping manifest).
In the call or e-mail, include the number of specimens being shipped, the
date the shipment will be sent, and if applicable, the FedEx tracking
number. Do not e-mail or fax the shipping manifest (the manifest is
included in the shipment).
3.5.
Track the shipment by using the FedEx tracking number (10–12 digits) on
the airbill. Tracking can be done through the Web site
(http://www.fedex.com) or by calling 1-800-GO-FEDEX.
If a problem is identified, please notify
Stanford HIV Genotyping Laboratory: 650-725-7165
and
Richard Kline (CDC): 404-639-4958
3.6.
The Stanford laboratory will contact the shipping laboratory if expected
shipments are not received.
4. Preliminary procedures for shipping to a locally contracted
genotyping laboratory
Follow the same procedures, substituting the locally contracted laboratory’s
contact information for the Stanford laboratory’s contact information (see 1.3 and
1.6).
August 2007
Appendix E
13-39
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
5. Packing procedures for shipping to a locally contracted genotyping
laboratory
Follow the procedures listed above, substituting local procedures as applicable
and substituting the locally contracted laboratory for the Stanford laboratory.
6. Procedures for shipping from the processing laboratory to a locally
contracted genotyping laboratory
Follow the procedures listed above, substituting local procedures as applicable
and substituting the locally contracted laboratory for the Stanford laboratory.
7. Procedures for local transport from the processing laboratory to a
locally contracted genotyping laboratory
7.1.
Follow the procedures listed above or substitute local procedures as
discussed with Richard Kline at CDC to ensure that specimens remain
frozen during transport and until ready for genotyping at the genotyping
laboratory. Always include a copy of the shipping manifest in the
shipment.
7.2.
Whenever specimens are transported, send a copy of the specimen manifest
to Richard Kline at CDC through the SDN (preferred) or the US Postal
Service. On the manifest, indicate the date that the specimens were shipped
to the genotyping laboratory. Do not e-mail or fax the shipping manifest
to CDC or the genotyping laboratory.
Mailing Address:
Attn: Richard Kline
Centers for Disease Control and Prevention
1600 Clifton Rd, NE, MS E-47
Atlanta, GA 30333
Phone: 404-639-4958
7.3.
Transport specimens only Monday through Thursday, unless local
guidelines specify otherwise. If local HIV surveillance or laboratory staff
are not personally handling the transport, do not transport specimens
during the weeks of Thanksgiving, Christmas, New Year’s, July Fourth, or
major local holidays.
7.4.
Track the shipment through FedEx’s or another courier’s tracking system.
If there are problems with the transfer, please notify
Richard Kline (CDC): 404-639-4958
and
the appropriate personnel at the genotyping laboratory
Develop an acknowledgment system so that the genotyping laboratory
informs the shipping laboratory when the shipment has arrived.
13-40
Appendix E
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
8. Local transfer from the processing area to the genotyping area
within one laboratory (i.e., the HIV diagnostic testing and genotyping
for HIV drug resistance are performed within the same laboratory)
If HIV testing and genotyping are performed in the same laboratory, diagnostic
testing is complete, and aliquots are identified as VARHS specimens, do the
following:
8.1.
Send a copy of the shipping manifest (Appendix E-2) to Richard Kline at
CDC through the SDN (preferred) or the US Postal Service. On the
manifest, indicate the date that the specimens were shipped to the
genotyping laboratory. Do not e-mail or fax the shipping manifest to CDC
or the genotyping laboratory.
Mailing Address:
Attn: Richard Kline
Centers for Disease Control and Prevention
1600 Clifton Rd, NE, MS E-47
Atlanta, GA 30333
Phone: 404-639-4958
8.2.
Ideally, the initial freezing of specimens should be done in a freezer
convenient to the genotyping laboratory so that it will not be necessary to
transfer frozen specimens.
8.3.
If frozen specimens are to be transferred from a freezer in one area to a
freezer in another area, a biohazard bag, cooler, and dry ice or cool packs
should be ready before the specimens are removed from the freezer. Place
the specimens (in their storage box) in the biohazard bag. Place the bag in
the cooler with dry ice or cool packs and transport as quickly as possible to
the other freezer.
8.4.
If there are problems with the transfer, please notify
Richard Kline (CDC): 404-639-4958
and
the appropriate personnel at the genotyping laboratory
August 2007
Appendix E
13-41
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix E-1. Training and Certification for Shipping Infectious
Substances
The following are some of the companies that provide training in shipping dangerous
goods. CDC does not endorse any particular company.
13-42
•
FedEx
1-800-GO-FEDEX
3-day IATA-based training
Covers all hazardous materials
Cost: ~$550
•
Saf-T-Pak
1-800-814-7484
Specifically for infectious and diagnostic substances and dry ice
3 options: 1-day seminar, on-site program, or interactive CD (can be
completed in 3–5 hours)
Certificate: valid for 2 years or until regulations change
Cost: ~$250
•
Viking Packing Specialist (Oklahoma)
1-800-788-8525; Contact: David Weilert
Monthly seminars in Tulsa
Covers all 9 classes of hazardous materials
Covers shipping according to IATA instructions
Certificate: good for 2 years
Cost: ~$300 per person
Group classes in local area: ~$3,000 plus travel costs
Appendix E-1. Training and Certification for Shipping Infectious Substances
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix E-2. CDC VARHS Shipping Manifest
Stanford Hospital and Clinics
300 Pasteur Drive
Stanford, CA 94035
CDC VARHS Shipping Manifest
Clinical Virology Laboratory @ Hillview
(650) 498-5575
Directors: R. Sibley, MD / B. Patterson, MD
Date specimens sent to Stanford: ____________
Link project number
(VARHS ID number)
Draw Date
Freeze Date
Serum or Plasma
(CIRCLE)
Volume
(if < 1 mL)
Stanford Laboratory
number
(STANFORD USE)
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Serum or Plasma
Shipping Instructions: 1) Call Stanford Virology Laboratory (650) 725-7165 when package is sent (keep a record of tracking number)
2) Complete this manifest form and include a copy with the specimens
3) Package and ship on Monday, Tuesday, or Wednesday only
4) Ship to:
Attn: Virology Laboratory Specimen Processing
Stanford Clinical Lab at Hillview
3375 Hillview Ave
RM 2401
Palo Alto, CA 94304-1204
Mail hard copy of the report to:
Attn: ______________________________________________________
Location ___________________________________________________
Street Address ______________________________________________
City_______________________________________________________
State ___________________ ZIP code
____________________________
Contact person name and phone number: _______________________________________; (
) __ __ __ - __ __ __ __
-----------------------------------------------------------------------------------------------------------------------------------------------------------------Stanford Virology Test Code: AVRT
For office use only:
Billing Done: _______________
Original: Box #_____________
Extract:: Box #_____________
Product: Box #_____________
August 2007
Appendix E-2. CDC VARHS Shipping Manifest
13-43
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix E-3. Stanford Laboratory’s Return of Shipping
Container
Sender: Attach return FedEx airbill. Complete all sections except the date, which will be
completed at the Stanford laboratory. See example below.
Stanford Virology Receiving Desk: Give the empty shipping container, packing materials,
and the return FedEx airbill to Hina, in Virology, for return to sender.
13-44
Appendix E-3. Stanford Laboratory’s Return of Shipping Container
August 2007
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Appendix F
VARHS Data Elements
Table 1
The following data elements are used for estimations of the national prevalence and
incidence of transmitted HIV-1 drug resistance and distribution of HIV-1 subtypes and for
making estimates for major subpopulations.
Note: Most of the data elements are collected through routine HIV case surveillance.
HIV-1 Drug
Resistance
Prevalence
Data Element
HIV-1 Subtype
Distributions
Demographic Data
Age
X
X
Sex
X
X
Race/ethnicity
X
X
Transmission category for HIV infection
X
X
Country of origin
X
X
Current state of residence
X
X
State of residence at HIV diagnosis
X
X
HIV pol gene nucleotide sequence
X
X
Mutation-specific assays
X
X
Laboratory Data
Previous HIV Testing Data
Date of first HIV test
X
Date of first positive HIV test
X
Date of last negative HIV test
X
Clinical Data
Date of AIDS diagnosis
X
CD4 counts
X
Dates of CD4 counts
X
Viral load
X
Dates of viral loads
X
Antiretroviral agents used
X
Start/end dates of antiretroviral agent use
X
Opportunistic infection(s) diagnosed
X
Date(s) of opportunistic infection diagnosis
X
August 2007
Appendix F
13-45
Technical Guidance for HIV/AIDS Surveillance Programs — Variant, Atypical, and Resistant HIV Surveillance (VARHS)
Table 2. Required Data Elements for Specimen Tracking
The following required laboratory data elements are used for local tracking of specimens,
evaluating problems with amplification of HIV for genotyping, supporting plans to
optimize specimen handling processes for surveillance purposes, and evaluating problems
with contamination.
Name
SPECIMEN ID
DRAWDTTM
SPECSOURCE
ACCESNUM
TUBE TYPE
BLDCOMP
BLDLAB
VOLGENO
GFRZ1DTM
NOT SENT
AMPLIFY
Label
VARHS ID number
Date/time of blood draw
Was specimen from a VARHS site or a commercial/private laboratory?
Laboratory accession number (if applicable)
Blood collection method
Type of specimen sent from collection site
Type of specimen sent for resistance test
Volume collected for genotype aliquot
Date/time of first freeze of aliquot
Was specimen sent for genotyping?
Was this specimen amplified?
Table 3. Optional Data Elements for Specimen Tracking
The following laboratory data elements are optional unless low amplification rates
(<90%) are seen in a particular surveillance area. In this case, all of the specimen tracking
data elements listed in Table 3, in addition to Table 2, will be required. The additional
elements must be collected until the amplification problem has resolved or until CDC can
conclude that the problem is not associated with specimen handling/storage procedures.
Name
COURDTTM
GRESDATE
DRECDTTM
CENTDTTM
SEPDTTM
ALIQDTTM
VOLUME
COND
SPECIMEN FROZEN
GFRZ2+YN
GTHW1DTM
GFRZ2DTM
GSHPDATE
BFRZ1DTM
BTHW1DTM
BFRZ2DTM
VOLBACK
13-46
Label
Date/time of courier pick-up from collection site
Date/time genotyping results received at DOH
Date/time of receipt in diagnostic laboratory
Date/time of centrifugation
Date/time of separation
Date/time of aliquoting
Volume of serum/plasma after separation
Specimen condition
Was this specimen frozen prior to aliquoting?
Was the genotyping aliquot thawed or refrozen?
Date/time of first thaw of genotyping aliquot
Date/time of second freeze of genotyping aliquot
Date of shipment to genotyping laboratory
Date/time of first freeze of local back-up aliquot
Date/time of first thaw of local back-up aliquot
Date/time of second freeze of local back-up aliquot
Volume of local back-up aliquot
Appendix F
August 2007
| File Type | application/pdf |
| File Title | HIV_Surveillance_Guidelines_Vol_1.book |
| Author | bnk5 |
| File Modified | 2009-11-02 |
| File Created | 2008-02-12 |