- No FAQs found
- ABL Kinase Domain Mutation in CML, Cell-based
- ABO Group and Rh Type
- Acid-Fast Bacillus (AFB) Identification, Sequencing and Stain, Paraffin Block
- ADAMTS13 Activity with Reflex to ADAMTS13 Inhibitor
- Alcohol Metabolites, Quantitative, Urine
- Alpha-Globin Common Mutation Analysis
- Alpha-Globin Gene Deletion or Duplication
- Alpha-Globin Gene Sequencing
- Anti-Müllerian Hormone AssessR™
- Anti-PF4 and Serotonin Release Assay (SRA) for Diagnosing Heparin-induced Thrombocytopenia/Thrombosis (HIT/HITT)
- Antiphospholipid Antibodies
- ASCVD Risk Panel with Score
- Autoimmune Epilepsy Evaluation
- Autoimmune Diseases, Tests for
- Bordetella pertussis toxin (PT) antibody
- B-cell and T-cell Clonality Assays by PCR
- B-Type Natriuretic Peptide (BNP)
- BCR-ABL1 Gene Rearrangement, Quantitative PCR
- Beta-Globin Complete
- Biotin: Interference with Laboratory Assays
- BRCAvantage®, Ashkenazi Jewish Screen
- BRCAvantage®, Rearrangements
- BRCAvantage™, Comprehensive
- BRCAvantage™, Single Site
- CDH1 Sequencing and Deletion/Duplication
- Clostridium difficile Diagnostic Testing
- C1 Inhibitor, Protein and Functional Tests
- Calreticulin (CALR) Mutation Analysis
- Carbapenem Resistant Enterobacteriaceae Culture Screen
- Cardio IQ Lipoprotein Fractionation, Ion Mobility
- CardioIQ® Insulin Resistance Panel with Score
- Cervical Cancer, TERC, FISH
- CFvantage® Cystic Fibrosis Expanded Screen
- Chlamydia trachomatis, TMA
- Chlamydia trachomatis/Neisseria gonorrhoeae RNA, TMA
- Chromosomal Microarray, POC, ClariSure®, Oligo-SNP
- Chromosomal Microarray, Postnatal, ClariSure® Oligo-SNP
- Chromosome Analysis and AFP with Reflex to AChE, Fetal Hgb, Amniotic Fluid
- Chromosome Analysis, Amniotic Fluid
- Chromosome Analysis, Blood
- Chromosome Analysis, Blood with Reflex to Postnatal, ClariSure® Oligo-SNP Array
- Chromosome Analysis, Chorionic Villus Sample
- Chromosome Analysis, High Resolution
- Chromosome Analysis, High Resolution with Reflex to Postnatal, ClariSure® Oligo-SNP Array
- Chromosome Analysis, Mosaicism
- Chromosome Analysis, Neonatal Blood
- Chromosome Analysis, Sister Chromatid Exchange
- Chromosome Analysis, Tissue
- Chromosome DEB Assay for Fanconi anemia
- Chronic Lymphocytic Leukemia (CLL) - Diagnostic and Prognostic Testing
- Culture, Fungus
- Culture, Urine, Routine
- Cystic Fibrosis Screen
- Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) PCR
- Cytomegalovirus (CMV) IgG avidity
- D-Dimer, Quantitative
- Dementia, Secondary Causes
- Dengue Virus Testing
- Diagnosis of Intestinal Parasites
- Drug Monitoring, Antidepressants, With Confirmation, Urine and Serum
- Drug Testing, General Toxicology (Blood, Urine, or Serum)
- Drug Toxicology Alcohol Metabolite, with Confirmation, Oral Fluid
- Drug Toxicology Monitoring, Oral Fluid Testing
- Factor V (Leiden) Mutation Analysis
- Factor VIII Activity, Clotting
- Familial Hypercholesterolemia (FH) Panel
- Familial Hypercholesterolemia (FH) Single Site
- Familial Mediterranean Fever Mutation Analysis
- First Trimester Screen, hCG
- First Trimester Screen, Hyperglycosylated hCG (h-hCG)
- FISH, Angelman
- FISH, MET Amplification
- FISH, Myeloma, 17p-, rea 14q32 with Reflexes
- FISH, Prader-Willi
- FISH, Prenatal Screen
- No FAQs found
- Helicobacter pylori (H pylori) Antibody Discontinuation
- Heparin, Anti-Xa
- Hepatitis B Surface Antibody, Quantitative
- Hepatitis B Surface Antigen, Quantitative, Monitoring
- Hepatitis C Antibody with Reflex to HCV RNA, PCR with Reflex to Genotype
- Hepatitis C Viral RNA Genotype 1 NS5A Drug-resistance
- Hepatitis C Viral RNA Genotype 3 NS5A Drug Resistance
- Hepatitis C Viral RNA NS3 Drug Resistance
- Hepatitis C Viral RNA, Genotype, LiPA
- Hepatitis C Virus Antibody and RNA Testing
- Hereditary Cancer Panels: MYvantageTM Hereditary Comprehensive Cancer Panel and GIvantageTM Hereditary Colorectal Cancer Panel
- Hereditary Hemochromatosis DNA Mutation Analysis
- Herpes Simplex Virus (HSV) Type-Specific IgG Antibodies
- Herpes Simplex Virus Type 2 (HSV-2) IgG Inhibition, ELISA
- HIV Pre-exposure Prophylaxis (PrEP) Testing
- HIV-1 Coreceptor Tropism, Proviral DNA
- HIV-1 Coreceptor Tropism, Ultradeep Sequencing
- HIV-1 Integrase Genotype
- HIV-1 Resistance, Proviral DNA (RTI, PI, Integrase Inhibitors)
- HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes
- HPV mRNA E6/E7
- Infliximab and Adalimumab Drug and Anti-drug Antibody Testing
- Influenza A and B Antigen, Immunoassay
- Influenza Type A and B Antibodies
- Insulin, Intact, LC/MS/MS
- Integrated Screen, Part 1
- Integrated Screen, Part 2
- Intrinsic Factor Blocking Antibody
- No FAQs found
- No FAQs found
- LDL Cholesterol Calculations
- LeukoVantage® Myeloid Neoplasm Mutation Panels
- Lupus Anticoagulant (LA) Evaluation with Reflex
- Maternal Serum AFP
- Melanoma, BRAF V600E and V600K Mutation Analysis, THxID®
- Metanephrines, Fractionated, Free, LC/MS/MS, Plasma
- Methylenetetrahydrofolate Reductase (MTHFR), DNA Analysis
- Microalbumin (Urinary Albumin Excretion)
- Myeloproliferative Neoplasm Diagnosis: Molecular Evaluation
- No FAQs found
- Pain Management and CYP2D6/CYP2C19
- Pain Management Antipsychotics, With Confirmation, Serum and Urine
- Pain Management, Naltrexone, Quantitative, Urine
- Partial Thromboplastin Time, Activated (aPTT)
- Penta Screen
- Pharmacogenomics Panel
- PIK3CA Mutation Analysis
- Platelet Antibody Screen (Indirect)
- PNH with FLAER (High Sensitivity)
- Prothrombin Time with INR
- PTH, Intact and Calcium
- Streptococcus pneumoniae (Pneumococcal) Antibody Tests
- Saccharomyces cerevisiae Antibodies (ASCA) (IgG, IgA)
- SARS-CoV-2 Serology (COVID-19) Antibody (IgG), Immunoassay
- Sequential Integrated Screen, Part 1
- Sequential Integrated Screen, Part 2
- Serum Integrated Screen, Part 1
- Serum Integrated Screen, Part 2
- Serum Pregnancy Tests
- Sickle Cell Screen
- Stepwise, Part 1
- Stepwise, Part 2
- SureSwab® Trichomonas vaginalis RNA, Qualitative TMA
- SureSwab®, Candidiasis, PCR
- TP53 Sequencing and Deletion/Duplication
- T4, Free
- Tamoxifen and Metabolites, LC-MS/MS
- Testosterone Testing
- Total Testosterone, LC/MS/MS
- Triple Screen
- No FAQs found
- No FAQs found
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HIV-1/2 Antigen and Antibodies, Fourth Generation, with ReflexesTest code(s) 91431(X)
Question 1. Are these particular tests appropriate for use in infants below the age of 2 years?
No. The HIV antigen/antibody assay listed above detects HIV antibodies that could be passively transferred from infected mothers to their infants. The appropriate tests to aid in the diagnosis of infant HIV infection include1,10:
- HIV-1 RNA, Qualitative TMA (test code16185[X])
- HIV-1 DNA, Qualitative PCR (test code 8401[X])
- HIV-2 DNA-RNA, Qualitative RT-PCR (test code 34977[X])
Question 2. Who should be screened for the presence of HIV infection?
The latest (2006) Centers for Disease Control and Prevention (CDC) recommendations for HIV testing of individuals encountered in healthcare settings include2:
- Routine, rather than behavior risk-based, HIV screening for all patients aged 13-64 years unless the prevalence of infection is extremely low (<1 in 1000 persons)
- Opt-out testing (ie, HIV testing performed unless patient declines)
- Persons engaging in risk behaviors associated with HIV acquisition should be screened for HIV infection at least annually
The US Preventive Services Task Force (USPSTF) recommends clinicians screen for HIV infection in adolescents and adults aged 15 to 65. Younger adolescents and older adults who are at increased risk should also be screened.3
Question 3. How does the HIV antigen/antibody (fourth-generation) screening test (test code 91431[X]) differ from an HIV antibody (third-generation) screening test (formerly available as test code 19728[X])?
HIV antigen/antibody fourth-generation-based screening tests can simultaneously detect both HIV-1 antigen (ie, viral protein) and HIV-1/2 antibodies, whereas HIV-1/2 antibody third-generation-based screening tests detect only antibodies. Third-generation test results are considered repeatedly reactive only after a person has developed detectable levels of antibody in their serum or other body fluid. Because third-generation tests detect only antibodies to HIV, they cannot detect HIV infection during acute infection—the period after virus acquisition when viral protein (HIV-1 antigen) may be detectable but antibodies to HIV are not.4 In contrast, fourth-generation HIV-1/2 testing methods can detect HIV-1 antigen as well as HIV-1 and HIV-2 antibodies.
Thus fourth-generation-based screening tests can detect HIV during a portion of the acute phase and all of the chronic phase of the disease. This ability has substantial individual and societal benefits. The patient benefits in that he/she can be more quickly evaluated for administration of appropriate antiviral medications, which may reduce the adverse early impacts of infection. Society benefits because actions can be taken to reduce HIV transmission. Individuals with acute HIV infection have much higher viral loads, making them more likely to transmit the virus. However, if individuals are diagnosed during the acute phase of the illness, they can be counseled regarding risk-reduction practices and can reduce their viral load with antiviral medication. Both of these actions reduce the likelihood of transmission to uninfected partners.
The CDC recommends using a fourth generation HIV antigen/antibody test for screening and diagnosis because it can detect HIV during both the acute and chronic phases of infection.5
Question 4. How long after exposure can fourth-generation tests effectively rule out HIV infection?
A study using a variety of HIV-1 seroconversion sample panels, in conjunction with statistical modeling, estimated that half of patients become repeatedly reactive on fourth-generation testing within 18 days after HIV infection; more than 99% have reactive results within 45 days after HIV acquisition. Therefore, HIV infection is very unlikely (ie, less than 1%) in patients with negative fourth-generation test results at least 45 days after the most recent exposure.11
Question 5. What is the CDC-recommended testing algorithm for the diagnosis of HIV infection?
The key concepts associated with the 2014 CDC recommendations are illustrated here.5
Question 6. Why does the CDC no longer recommend the HIV-1 Western blot test as the supplemental antibody test?
The CDC no longer recommends using the Western blot technique to confirm the presence of HIV-1 antibodies in repeatedly reactive specimens because:
- The HIV-1/HIV-2 antibody differentiation test is more sensitive than the Western blot early in infection.6
- The HIV-1/HIV-2 antibody differentiation test can be performed more rapidly than can the Western blot method, so the turnaround time for confirmation of HIV infection is shorter.
- Studies have shown that the HIV-1/HIV-2 antibody differentiation test more accurately differentiates HIV-1 and HIV-2 infections.7 HIV-2 infection, while rare in the United States, is most commonly seen in persons from West Africa. It's important to differentiate HIV-1 from HIV-2, as HIV-2 may not respond to some HIV medications.9
Question 7. How is the following combination of HIV test results interpreted?
A patient with these test results…
A patient with these test results…
…has acute HIV-1 infection, confirmed by detection of HIV-1 RNA prior to the development of HIV-1 antibodies.
Question 8. What causes a biological false-positive HIV screening test?
The precise reason for a biological false-positive result in any individual specimen is not likely to be definitively known. A few of the causes hypothesized in the medical literature include recent administration of selected vaccines, presence of HLA-DR antibodies, presence of rheumatoid factors, reactive RPR, hypergammaglobulinemia, cross-reactive immune response to other exogenous and endogenous retroviruses, and autoimmune conditions.
Although there are occasional biological false-positive results observed with HIV screening tests, as with all screening tests, the specificities of the FDA-approved HIV screening tests are very high (>99%). The potential adverse effects of a biological false-positive screening test result are ameliorated by use of this CDC-recommended multi-step testing algorithm. Test results are only considered to support the diagnosis of HIV infection when the screening test results are repeatedly reactive and either supplemental test (ie, HIV-1/2 antibody differentiation or HIV-1 RNA) is positive.5
Question 9. Which follow-up test is recommended when the screening test is Repeatedly Reactive, but the confirmatory tests are both negative?
Follow-up testing is generally not recommended. Additional testing is only indicated if the patient is thought to be very recently infected and/or the patient is at continued risk for HIV exposure. Refer to cdc.gov for the latest CDC recommendations on this subject.
Question 10. Is pregnancy associated with a higher frequency of biological false-positive HIV screening test results?
There have been anecdotal reports of pregnancy being associated with a higher frequency of biological false-positive HIV screening test results. This anecdotal association may have been due to an initially greater frequency of testing of pregnant women prior to issuance of the 2006 CDC HIV testing recommendations. A more recent large epidemiologic study using a third-generation HIV screening method did not demonstrate a greater propensity toward biological false positivity in pregnant subjects. In this study of more than 2 million third-generation HIV antibody screening tests, the false-positive rate was actually lower for pregnant women than for others (0.14% versus 0.21%).8
Question 11. Why does the laboratory require that a blood sample for HIV testing be collected in a separate tube?
HIV screening tests are extremely sensitive and can detect very low levels of circulating viral antibodies and/or antigens (fourth-generation test) in a patient’s sample. The laboratory requires a separate sample collection tube for HIV screening testing to help eliminate false-positive results that may be associated with pre-analytic sample handling during the performance of other requested tests. Minimizing pre-analytic sample handling issues is critical, given the clinical significance of a positive HIV test result.
Question 12. What percentage of patient specimens tested with the fourth-generation-based HIV diagnostic algorithm require being reflexed through the entire algorithm?
A retrospective unpublished evaluation of approximately 23,000 samples tested at Quest Diagnostics using the fourth-generation HIV screening algorithm found that only 0.16% required reflex testing through the final step in the CDC HIV diagnostic algorithm (ie, testing by the HIV-1 RNA assay).
- Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children—A Working Group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the use of antiretroviral agents in pediatric HIV infection [pages C-1 to C-6]. http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf.Accessed July 28, 2014.
- Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm.
- Screening for HIV: U.S. Preventive Services Task Force recommendation statement. Published April 2013. www.uspreventiveservicestaskforce.org/uspstf13/hiv/hivfinalrs.htm.Accessed July 28, 2014.
- Stekler JD, Branson BM. Detection of acute HIV infection: we can’t close the window. J Infect Dis. 2012;205:521-524.
- Branson BM, Owen SM, Wesolowski LG, et al for Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. http://stacks.cdc.gov/view/cdc/23447. Published June 27, 2014. Accessed June 27, 2014.
- Masciotra S, Luo W, Youngpairoj AS, et al. Performance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with specimens from HIV-1 seroconverters from the US and HIV-2 infected individuals from the Ivory Coast. J Clin Virol. 2013;58(suppl 1): e54-58. doi:10.1016/j.jcv.2013.07.002.
- Nasrullah M, Ethridge SF, Delaney KP, et al. Comparison of alternative interpretive criteria for the HIV-1 Western blot and results of the Multispot HIV-1/HIV-2 Rapid Test for classifying HIV-1 and HIV-2 infections.
- J Clin Virol. 2011;52(suppl 1):S23-27. doi:10.1016/j.jcv.2011.09.020.
- Wesolowski LG, Delaney KP, Lampe MA, et al. False-positive human immunodeficiency virus enzyme immunoassay results in pregnant women. PLoS ONE. 2011;6(1):e16538. doi:10.1371/journal.pone.0016538.
- HIV-2 infection surveillance – United States, 1987-2009. MMWR. 2011;60:985-988. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6029a3.htm.
- Siberry GK. Preventing and managing HIV infection in infants, children, and adolescents in the United States. Pediatr Rev. 2014;35:268-286.
- Delaney KP, Hanson DL, Masciotra S, et al. Time until emergence of HIV test reactivity following infection with HIV-1: implications for interpreting test results and retesting after exposure. Clin Infect Dis. 2017;64:53-59.