INTEGRATING HIV AND HCV TESTING

HIV TEST PERFORMANCE FIGURE 1: LABORATORY MARKERS OF HIV INFECTION HIV RNA (plasma) HIV Antibody HIV p24 Ag IgM IgG Diagnosis of HIV infection requires conducting a series of tests, or testing algorithm, beginning with a series of antigen/antibody (Ag/Ab) and/or antibody (Ab) tests which may be, followed by nucleic acid test (NAT) that detects HIV RNA. Testing algorithms take advantage of the trade-offs between sensitivity and specificity. The first (screening) test should be highly sensitive, to minimize the chance that individuals with infection are missed. Positive tests should be followed by a different highly specific test to confirm infection. RNA appears very early in infection and remains detectable for months and/or until virally suppressed (solid blue line) Antigen (Ag) is the second marker to appear in infection, earlier than either IgM or IgG antibodies (red dotted line) Immunoglobulin M (IgM) antibodies appear third in infection and earlier than IgG antibodies (blue dashed line) Immunoglobulin G (IgG) antibodies are the last to appear in the course of an infection but remain detectable for months (blue dashed line) 0 10 20 Days Since Infection 30 40 50 60 70 80 90 100 Figure adapted from Delaney et al., CID 2017:64 and provided by M. Owen, NCHHSTP, CDC.

Laboratory-Based Tests HIV TEST PERFORMANCE HIV TESTS: MEDIAN WINDOW PERIOD IN DAYS BASED ON PLASMA Laboratory-Based Tests POC Rapid Tests Ag/Ab 17.8 19.2 IgM/IgG 23.1 29.3 IgG 30.6 31.1 The newest and most sensitive tests for HIV detect both HIV antigen and HIV antibodies (Ag/Ab tests) These tests have a window period of approximately 2.5 weeks. Examples of Ag/Ab tests include: Laboratory Based: ARCHITECT, BioPlex 2200, GS Combo, Siemens Combo Rapid Point of Care: Determine Tests that detect both IgG and Immunoglobulin M (IgM) antibodies IgM antibodies appear earlier in infection than IgG antibodies. These tests have a window period of approximately 3 weeks. Examples of IgG/IgM tests include: Laboratory Based: ADVIA, GS HIV1/HIV2 Plus O, VITROS Rapid Point of Care: INSTI and Uni-Gold Tests that detect only Immunoglobulin G (IgG) antibodies IgG antibodies appear later in the course of infection. Therefore tests that detect IgG only have the longest window periods at approximately 5 weeks. Examples of IgG only tests include: Laboratory Based: Western blot Rapid Point of Care: Complete, STAT-PAK, DPP, OraQuick, and Reveal NAT tests directly detect HIV. The median window period for HIV NATs is under 2 weeks. Test sensitivity is highest when used with plasma and serum samples. Test sensitivity is lower with whole blood. Test sensitivity is lowest when used on oral fluid.

HCV TEST PERFORMANCE FIGURE 2: LABORATORY MARKERS OF HCV INFECTION HCV RNA Anti-HCV Diagnosis of HCV requires an antibody test to be performed, and if positive, followed by a NAT that detects HCV RNA. HCV antibody tests have a window period between 8-11 weeks. HCV RNA can be detected approximately 2–3 weeks after infection. HCV core Ag Window Phase 0 10 20 30 40 50 60 70 80 90 100 days Days Since Infection Figure provided by S. Kamili, DVH, CDC.

TESTING STRATEGIES Laboratory-Based Testing Specimen sent to laboratory for testing Sequence of tests performed Laboratory Testing for the Diagnosis of HIV Infection Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians Earlier detection than possible with POC Point-of-Care Rapid Testing Testing where client receives services Various supplemental testing methods Two basic testing strategies Laboratory Testing: Laboratory testing involves obtaining a specimen from a patient and sending it to a laboratory for processing. Most laboratories use several different tests in a sequence (i.e. an algorithm) to diagnose HIV or HCV infection. Supplemental testing may be performed by the same laboratory or referred to another laboratory Depending on work flow, whether supplemental testing is required and whether supplemental testing is performed in house or referred, results may be available within hours or several days. Laboratory-based testing can detect infection earlier than rapid testing due to the shorter window periods for laboratory tests. If testing is performed by multiple laboratories because a specimen is referred or a second sample is required, the gains in earlier detection may be lost due to longer turnaround times. It is important to understand where each step of testing is performed and which tests are conducted in order to identify additional testing that may be required (e.g. to confirm infection), correctly interpret results, and to report accurately identified cases to public health surveillance. Point-of-Care Rapid Testing: Tests are conducted where the client receives services, with at least preliminary results available on the same day/visit. Positive test results are typically considered preliminary and usually require supplemental testing to confirm a diagnosis of HIV or HCV. Supplemental testing to confirm infection through 3 strategies: (1) use of a second rapid test (by a different manufacturer) at the point of care (available for HIV only); (2) by taking a blood specimen and sending it to a laboratory; or (3) by referral to another provider who can conduct supplemental testing, perhaps along with other tests needed for evaluation for treatment. If supplemental testing is conducted in a laboratory, final results are typically available within several days.

(using CDC-recommended serum/plasma algorithms) COMPARISON OF TESTING STRATEGIES Comparison Categories Laboratory-Based Testing (using CDC-recommended serum/plasma algorithms) Point-of-Care Rapid Testing (using CLIA-waived tests) HIV HCV Window period 2-3 weeks 8–11 weeks 3-5 weeks Detect acute infection Yes No Final results From a single specimen Negative results from single specimen; Positive results second specimen Testing for multiple infections Yes, multiple tests may be performed on single specimen No, additional specimens needed for other tests Timeframe for delivering results Several hours to days to final Negative results delivered same visit/day. Positive results, several hours to days to final FDA-approved specimen types Serum or plasma Whole blood, serum, or oral mucosal transudate (HIV only) Specimen collection Venipuncture Varies by test (venipuncture, finger stick, or oral fluid). Quality assurance Limited QA assurance by providers. Extensive QA by testing providers Integration may be achieved through use of either laboratory-based or point-of-care strategies. There are benefits and trade-offs associated with each strategy. Laboratory testing: For HIV window period for detection 2-3 weeks; HCV 8-11 weeks Can detect acute infection (for HCV requires interpretation with symptoms) May provide final results from a single specimen depending on laboratory capacity/platform, work flow. May be able to tests for multiple pathogens on single sample Results w/in several hours/ to several days Requires plasma or serum samples obtained via venipunture Testing providers have minimal QA requirements Rapid point-of-care testing For HIV window period for detection is 3-5 weeks; HCV 8-11 weeks Detection of acute HCV infection requires interpretation with symptoms Negative results from single sample; positive results require second specimens Tests for multiple pathogens require multiple samples and multiple tests Results same day/visit; final results several hours/days Serum, whole blood, oral fluid (HIV) samples More extensive QA for testing providers (e.g. temperature, lot control, staff proficiency testing, storage).

SELECTING A TESTING STRATEGY Population-Level Factors Client-Level Factors Program-Level Factors HIV and HCV Prevalence HIV and HCV Incidence HIV-2 prevalence Co-morbidity of HIV and HCV, and/ or with other conditions such as STDs and hepatitis B virus (HBV) Likelihood of acute HIV infection Likelihood of current HCV infection Likelihood that clients will return for results/linkage Understanding of the accuracy tests Acceptability of the testing strategy Appropriateness and relevance to client needs Cost to client for testing and treatment Readiness to engage in treatment Access to treatment Staff capabilities to conduct testing Staff perceptions and attitudes about strategy Feasibility of introducing strategy into existing workflow Laboratory capacity to implement required tests, including CDC- recommended testing algorithms Delivery of related prevention and treatment services such as HIV PrEP There are many factors for health departments to consider in deciding which strategy(ies) they should use. In general, health departments should use a strategy that: Ensures accurate and timely results Identifies HIV or HCV as early in the course of infection as possible (3) Helps to advance public health objectives (4) Is appropriate to addressing the needs and priorities of the target population(s) (5) Is consistent with the capacity of the testing/linkage providers A single testing strategy may not be appropriate in every situation, setting, or for every population. There may also be situations where integration of HIV and HCV testing serves the needs of the client, community and health department, and there may be other situations where integration does not. In making decisions about testing strategies, health should consider population-, client- and program-level factors.