Advances in HIV serology: Implications for clinical care

The detection of both established and acute HIV infection (AHI) is important for reducing HIV transmission. AHI is associated with very high viral loads, and the magnitude of the viral load correlates with the transmission risk


The detection of both established and acute HIV infection (AHI) is important for reducing HIV transmission. AHI is associated with very high viral loads, and the magnitude of the viral load correlates with the transmission risk. Detecting AHI is particularly important because acute infections account for 10% to 50% of transmission events.[1,2] In addition to the use of safe sexual practices, control of HIV transmission requires timely diagnosis, engagement into care, and rapid initiation of antiretroviral therapy to decrease HIV RNA levels to reduce transmission.[3,4]  

Immediately after HIV infection there is an eclipse period, lasting about 10 days, where no HIV markers are detectable in blood.[5] Approximately 10 days after infection, HIV RNA becomes detectable and the viral load increases during the ensuing weeks. HIV p24 antigen and HIV antibodies can be detected about 18 days after infection by fourth-generation immunoassays. These modern HIV p24 antigen/antibody assays, which are used throughout BC for HIV screening, detect infections about 4 to 5 days earlier than the older, third-generation assays that only detected HIV antibodies. Specimens reactive by fourth-generation immunoassays are automatically tested to determine if the HIV infection is acute or established. AHI cases have detectable HIV RNA and negative or indeterminate immunoblot results. 

Since 2009, the BC Centre for Disease Control Public Health Laboratory (BCCDC PHL), which performs most of the HIV screening and confirmatory testing in BC, has also been using pooled HIV RNA nucleic acid testing (NAT) as a strategy to identify AHI in very high-risk populations.[6] The BCCDC PHL also performs a limited number of HIV NAT tests to detect AHI in high-risk seronegative prenatal women and their neonates. In 2015, the BCCDC PHL switched to a fourth-generation immunoassay from third-generation, and in 2016 replaced the traditional HIV-1 specific Western blot with a rapid immuno-blot that differentiates between HIV-1 and -2 antibodies. The BCCDC PHL has demonstrated that use of a fourth-generation immunoassay reduces the test-negative window and improves the sensitivity for AHI detection relative to the older third-generation immunoassays. Pooled and individual NAT identified 37% (19/51) of AHI cases during a 15-month period when third-generation immunoassay screening was used (February 2014 to May 2015), while only 10% (6/61) of AHI cases were identified using NAT during a subsequent 15-month period when fourth-generation immunoassay screening was used (June 2015 to August 2016). Therefore, the utility of NAT for AHI diagnosis is significantly reduced when fourth-generation EIA is used as the primary HIV screening test.

Physicians should only request NAT testing from:
High-risk prenatal women and their neonates.
High-risk men who have sex with men (pooled NAT).
Patients with suspected acute HIV.

—Agatha Jassem, PhD, D(ABMM), FCCM
—Mel Krajden, MD, FRCPC

hidden


This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.


References

  1.     Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian cancer statistics 2015. Toronto, ON: Canadian Cancer Society; 2015. Accessed 7 March 2017. www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Can....
  2.     Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer 1996;77:2318-2324.
  3.     Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007;25:1329-1333.
  4.     BC Cancer. Hereditary Cancer Program referral form. Accessed 7 March 2017. www.bccancer.bc.ca/screening/Documents/HCP_Form-ReferralForm.pdf. 
  5.     Hilgart JS, Coles B, Iredale R. Cancer genetic risk assessment for individuals at risk of familial breast cancer. Cochrane Database Syst Rev 2012;(2):CD003721. 
  6.     National Institute for Health and Care Excellence (NICE). Familial breast cancer: Classification, care and managing of breast cancer and related risks in people with a family history of breast cancer. Published June 2013. Updated August 2015. Accessed 7 March 2017. www.nice.org.uk/guidance/cg164. 
  7.     Kuhl C, Weigel S, Schrading S, et al. Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: The EVA trial. J Clin Oncol 2010;28:1450-1457.
  8.     Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427-437.
  9.     Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: A prospective multicentre cohort study (MARIBS). Lancet 2005;365(9473):1769-1778.
  10.     Sardanelli F, Podo F, Santoro F, et al. Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the High Breast Cancer Risk Italian 1 Study): Final results. Invest Radiol 2011;46:94-105.
  11.     Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004;292:1317-1325.
  12.     Lowry KP, Lee JM, Kong CY, et al. Annual screening strategies in BRCA1 and BRCA2 gene mutation carriers: A comparative effectiveness analysis. Cancer 2012;118:2021-2030.
  13.     Cott Chubiz JE, Lee JM, Gilmore ME, et al. Cost effectiveness of alternating magnetic resonance imaging and digital mammography screening in BRCA1 and BRCA2 gene mutation carriers. Cancer 2013;119:1266-1276.
  14.     Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001;93:1633-1637.
  15.     Heemskerk-Gerritsen BA, Menke-Pluijmers MB, Jager A, et al. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: A prospective analysis. Ann Oncol 2013;24:2029-2035.
  16.     Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999;340:77-84.
  17.     van Dijk S, van Roosmalen MS, Otten W, Stalmeier PF. Decision making regarding prophylactic mastectomy: Stability of preferences and the impact of anticipated feelings of regret. J Clin Oncol 2008;26:2358-2363.
  18.     Friebel TM, Domchek SM, Neuhausen SL, et al. Bilateral prophylactic oophorectomy and bilateral prophylactic mastectomy in a prospective cohort of unaffected BRCA1 and BRCA2 mutation carriers. Clin Breast Cancer 2007;7:875-882.
  19.     Chai X, Friebel TM, Singer CF, et al. Use of risk-reducing surgeries in a prospective cohort of 1,499 BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 2014;148:397-406.
  20.     Graeser MK, Engel C, Rhiem K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2009;27:5887-5892.
  21.     Chiba A, Hoskin TL, Hallberg EJ, et al. Impact that timing of genetic mutation diagnosis has on surgical decision making and outcome for BRCA1/BRCA2 mutation carriers with breast cancer. Ann Surg Oncol 2016;23:3232-3238.
  22.     Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 2006;296:185-192.
  23.     Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346:1609-1615.
  24.     Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616-1622.
  25.     Tone AA, Salvador S, Finlayson SJ, et al. The role of the fallopian tube in ovarian cancer. Clin Adv Hematol Oncol 2012;10:296-306.
  26.     Cibula D, Widschwendter M, Majek O, Dusek L. Tubal ligation and the risk of ovarian cancer: Review and meta-analysis. Hum Reprod Update 2011;17:55-67.
  27.     Kwon JS, Tinker A, Pansegrau G, et al. Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol 2013;121:14-24.
  28.     Chiarelli AM, Prummel MV, Muradali D, et al. Effectiveness of screening with annual magnetic resonance imaging and mammography: Results of the initial screen from the Ontario high risk breast screening program. J Clin Oncol 2014;32:2224-2230.
  29.     Chart PL, Franssen E. Management of women at increased risk for breast cancer: Preliminary results from a new program. CMAJ 1997;157:1235-1242.

Agatha Jassem, PhD, (D)ABMM, FCCM, Mel Krajden, OBC, MD, FRCPC. Advances in HIV serology: Implications for clinical care. BCMJ, Vol. 59, No. 10, December, 2017, Page(s) 499 - BC Centre for Disease Control.



Above is the information needed to cite this article in your paper or presentation. The International Committee of Medical Journal Editors (ICMJE) recommends the following citation style, which is the now nearly universally accepted citation style for scientific papers:
Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected patients. N Engl J Med. 2002;347:284-7.

About the ICMJE and citation styles

The ICMJE is small group of editors of general medical journals who first met informally in Vancouver, British Columbia, in 1978 to establish guidelines for the format of manuscripts submitted to their journals. The group became known as the Vancouver Group. Its requirements for manuscripts, including formats for bibliographic references developed by the U.S. National Library of Medicine (NLM), were first published in 1979. The Vancouver Group expanded and evolved into the International Committee of Medical Journal Editors (ICMJE), which meets annually. The ICMJE created the Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals to help authors and editors create and distribute accurate, clear, easily accessible reports of biomedical studies.

An alternate version of ICMJE style is to additionally list the month an issue number, but since most journals use continuous pagination, the shorter form provides sufficient information to locate the reference. The NLM now lists all authors.

BCMJ standard citation style is a slight modification of the ICMJE/NLM style, as follows:

  • Only the first three authors are listed, followed by "et al."
  • There is no period after the journal name.
  • Page numbers are not abbreviated.


For more information on the ICMJE Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals, visit www.icmje.org

BCMJ Guidelines for Authors

Leave a Reply