Contents

Search

HIV laboratory testing

Indications: 1) signs/symptoms of acute retroviral infection 2) signs/symptoms of chronic HIV1 infection 3) opportunistic infection 4) severe, recurrent or persistent infection other than opportunistic infection - severe seborrheic dermatitis or new or severe psoriasis [6] 5) tuberculosis, hepatitis B, hepatitis C, STD, hemophilia 6) history of at risk behavior a) multiple partners b) men who have sex with men c) injection drug use d) sexual partner of person with at risk behavior 7) persons age 13-66 (unless prevalence < 0.1%) 8) known or suspected HIV1 exposure 9) victim of sexual assault 10) patient request 11) all pregnant women 12) child born to mother infected with HIV1 13) occupational exposure to blood/body fluid - test both source patient & exposed worker 14) blood donor, organ donor, semen donor Laboratory: 1) HIV screening is done with HIV1 EIA/ELISA or other rapid HIV test 2) confirmatory testing is done with HIV Ag/Ab Combo assay, followed by HIV1/HIV2 Ab differentiation assay & HIV1 RNA as indicated [6] 3) early detection of HIV1 acute retroviral syndrome may become standard of care - HIV1 RNA by nucleic acid amplification [2] - HIV 1+2 Ab & HIV1 p24 Ag in serum [15] - HIV1/HIV1 Ab differentiation assay [6] - HIV1 RNA is gold standard [13] 4) specific HIV1 Ab* are not detectable until 4-12 weeks after initial infection a) screening with HIV1 EIA/ELISA* for antibody to HIV1 (99% sensitivity & specificity) b) Oraquick Rapid HIV1 Antibody Test available 2003 c) HIV Ag/Ab Combo assay to detect both HIV1 p24 antigen & HIV1+HIV2 antibodies (FDA-approved 6/21/2010) - HIV 1+2 Ab & HIV1 p24 Ag in serum/plasma/blood - HIV-1/HIV-2 antibody differentiation assay if positive confirms diagnosis d) HIV1 p24 antigen in serum is generally positive just after onset of symptoms, before development of antibodies e) confirmatory HIV1 Western blot is NO LONGER DONE [6] - a positive western blot consisted of presence of bands for: - HIV1 p24 Ab in serum - HIV1 gp41 Ab in serum & - HIV1 gp120 Ab in serum or Ab in serum gp160 in serum f) seronegative HIV1 infections are rare, but potentially lethal [6] 5) quantitative HIV1 RNA levels a) reverse-trancriptase polymerase chain reaction (RT-PCR) b) branched chain DNA (bDNA) assay c) nucleic acid sequence-based assay (NASBA) d) high levels of HIV1 RNA (500,000- 21 million copies/mL) are detected in plasma before detection of specific HIV1 Ab e) the high level of viremia decreases 100-10,000 fold coincident with the development of the specific anti-HIV1 humoral immune response - it is thought that cytotoxic T-cells are responsible for this decline in HIV1 viral load f) post-seroconversion viral load (HIV RNA determined by PCR) is the best predicator of long-term prognosis g) post-seroconversion HIV RNA > 30,000 copies/mL are associated with a high risk of disease progression h) identification of acute HIV infection with quantitative HIV1 RNA levels combined with aggressive early treatment may 1] reduce severity of chronic infection 2] prevent transmission to sexual contacts [8] i) HIV1 viral load a) independent predictor of disease progression [3] b) poorly predicts decline in CD4 count [7] c) responds to initiating or changing therapy within 4-8 weeks (>= 1 log decrease in HIV RNA) d) a decrease in HIV RNA of more than 1 log is associated with treatment benefit j) frequent monitoring of HIV1 RNA levels for the 1st year to detect treatment failure [11] k) routine every 3-4 months & monthly after change in therapy 6) complete blood count (CBC) with differential a) lymphopenia may develop during acute seroconversion b) atypical lymphocytosis may follow resolution of symptoms associated with seroconversion c) anemia d) thromocytopenia [6] 7) serum chemistries (every 6-12 months) a) renal function tests b) serum transaminases c) serum glucose c) lipid panel 8) serology a) serologic testing for syphilis - testing for other STDs b) Toxoplasma gondii IgG c) Cytomegalovirus (CMV) IgG (high risk) d) hepatitis A serology, hepatitis B serology & hepatitis C serology e) varicella virus serology (high risk) [6] 9) CD4 count a) best predictor of risk of disease progression b) average rate of decline is 80-90/uL/year c) HIV1 viral load does NOT predict decline [7] d) routine every 3-4 months [6] e) CD4 count of < 200 cells/uL establishes diagnosis of AIDS [6] 10) tuberculin skin testing or Quantiferon TB test annually [6] unless PPD+ or with active tuberculosis 11) Papanicolaou (Pap) smear for women 12) glucose-6-phosphate dehydrogenase (G6PD) in erythrocytes (baseline) 13) HIV1 resistance testing, all HIV1 patients [6,11] 14) CCR5 gene mutation analysis (4 Loincs) - CCR5 gene mutation - CCR5 gene c.794-825del - variations in CCR5 are associated with susceptibility or resistance to HIV1 15) variations in CCR2 are associated with relative resistance to HIV1 - CCR2 gene p.Val64Ile 16) HIV1 coreceptor tropism testing a) determines eligibility for maraviroc (Selzentry) therapy by determinng variations in the HIV1 envelope V3 loop by PCR [10] b) HIV1 tropism testing determines ability of HIV1 isolate to infect & replicate in monocytes [9] 17) see ARUP consult [12] Interferences: - Covid-19 infection may cause false-positive HIV screening tests (4th generation) [19] Notes: The requirement for informed consent for HIV testing has been repealed, effective Aug 17 2009. Confidentiality for HIV testing to be consistent with HIPPA guidelines for other laboratory tests. [5] Opt-out strategy results in highest HIV testing acceptance HIV testing performed at only 1% of physician office visits made by young men during 2009-2012 despite CDC recommendations for routine HIV1 testing of adolescents & adults Previously: - testing could be done only after informed consent - legal guardians could sign consent - sexually active children over 12 could give their own consent - only the person who gave consent could be given the results of the test - others could be notified only is written permission is obtained from the person tested

Related

human immunodeficiency virus-1 (HIV-1)

Specific

HIV 1+2 Ab in serum HIV-1 + HIV-2 Ab + HIV-1 p24 Ag HIV1 nucleic acid HIV1 p24 antigen HIV1 RNA integrase gene mutations HIV1 RNA protease gene mutations HIV1 RNA reverse transcriptase & protease gene sequencing HIV1 RNA reverse transcriptase gene mutations HIV1 serology; HIV1 antibody (HIV1 EIA/ELISA, immunoblot) HIV1/HIV2 Ab differentiation assay human immunodeficiency virus-1 (HIV1) western blot rapid HIV test (point of care HIV test)

General

clinical microbiology test

References

  1. Veterans Administration, Mather CA
  2. Truong HH et al, Routine surveillance for the detection of acute and recent HIV infections and transmission of antiretroviral resistance. AIDS 2006, 20:2193 PMID: 17086059 - Priddy FH et al, Detection of acute HIV infections in an urban HIV counseling and testing population in the United States. J Acquir Immun Defic Syndr 2006 (ePub)
  3. Centers for Disease Control and Prevention, Missed Opportunities for earlier diagnosis of HIV infection - South Carolona, 1997-2005 MMWR Morb Mortal Wkly Rep 2006, 55:1269 PMID: 17136020
  4. Voetsch A et al HIV Testing Among High School Students - United States, 2007 MMWR June 26, 2009 / 58(24);665-668 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5824a3.htm
  5. Federal Register: July 16, 2009 (Volume 74, Number 135) Rules and Regulations: Page 34500-34503] From the Federal Register Online via GPO Access http://wais.access.gpo.gov DOCID:fr16jy09-3 DEPARTMENT OF VETERANS AFFAIRS Elimination of Requirement for Prior Signature Consent and Pre- and Post-Test Counseling for HIV Testing ACTION: Final rule. http://edocket.access.gpo.gov/2009/E9-16898.htm
  6. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  7. Rodriguez B et al, Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 2006, 296:1498 PMID: 17003398
  8. Journal Watch 25(11):88, 2005 Pilcher CD, Fiscus SA, Nguyen TQ, Foust E, Wolf L, Williams D, Ashby R, O'Dowd JO, McPherson JT, Stalzer B, Hightow L, Miller WC, Eron JJ Jr, Cohen MS, Leone PA. Detection of acute infections during HIV testing in North Carolina. N Engl J Med. 2005 May 5;352(18):1873-83. PMID: 15872202
  9. O'Brien WA et al HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain Nature 1990, 348:69-73 PMID: 2172833
  10. HIV-1 Coreceptor tropism Quest Diagnostics http://www.nicholsinstitute.com/Documents/Library/TS2457-HS.pdf
  11. Thompson MA et al Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society- USA Panel JAMA. 2010;304(3):321-333 PMID: 20639566 http://jama.ama-assn.org/cgi/content/full/304/3/321
  12. ARUP Consult: Human Immunodeficiency Virus - HIV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/human-immunodeficiency-virus - Human Immunodeficiency Virus in Adults and Adolescents Testing Algorithm https://arupconsult.com/algorithm/human-immunodeficiency-virus-adults-testing-algorithm
  13. Centers for Disease Control and Prevention Detection of Acute HIV Infection in Two Evaluations of a New HIV Diagnostic Testing Algorithm -- United States, 2011-2013. MMWR. 62(24);489-494. June 21, 2013. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6224a2.htm
  14. Branson BM et al Laboratory Testing for the Diagnosis of HIV Infection. Updated Recommendations. June 27, 2014 http://www.cdc.gov/hiv/pdf/HIVtestingAlgorithmRecommendation-Final.pdf - Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens. http://www.cdc.gov/hiv/pdf/testingHIValgorithmQuickRef.pdf
  15. FDA News Release. July 23, 2015. FDA approves diagnostic test to differentiate between types of HIV infection. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455813.htm
  16. Montoy JC, Dow WH, Kaplan BC. Patient choice in opt-in, active choice, and opt-out HIV screening: Randomized clinical trial. BMJ 2016 Jan 19; 352:h6895 PMID: 26786744 Free PMC Article http://www.bmj.com/content/352/bmj.h6895
  17. Ham DC, Huang Y, Gvetadze R, Peters PJ, Hoover KW. Health Care Use and HIV Testing of Males Aged 15-39 Years in Physicians' Office - United States, 2009-2012 MMWR Morb Mortal Wkly Rep 2016;65:619-622 https://www.cdc.gov/mmwr/volumes/65/wr/mm6524a3.htm
  18. Branson BM et al Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings. MMWR. Recommendations & Reports. Sept 22, 2006 / 55(RR14);1-17 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm
  19. Gudipati S et al. Increase in false-positive fourth-generation human immunodeficiency virus tests in patients with coronavirus disease 2019. Clin Infect Dis 2023 May 9; [e-pub]. PMID: 37158382 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad264/7157537
  20. Saag MS HIV Infection - Screening, Diagnosis, and Treatment. N Engl J Med 2021; 384:2131-2143. June 3 PMID: 34077645 https://www.nejm.org/doi/full/10.1056/NEJMcp1915826
  21. Rose MR, MChida NM, Jones JL Fourth-Generation HIV Testing JAMA. Published online December 1, 2023 PMID: 38039053 https://jamanetwork.com/journals/jama/fullarticle/2812672