Future VirologyVol. 8, No. 6 EditorialFree AccessChallenges in identifying and estimating undiagnosed HIV infectionAmy Lansky, Joseph Prejean & Irene HallAmy Lansky* Author for correspondenceDivision of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention (NCHHSTP), Centers for Disease Control & Prevention (CDC), Mailstop D-21, 1600 Clifton Rd, Atlanta, GA 30333, USA. .Search for more papers by this authorEmail the corresponding author at all0@cdc.gov, Joseph PrejeanDivision of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention (NCHHSTP), Centers for Disease Control & Prevention (CDC), Mailstop D-21, 1600 Clifton Rd, Atlanta, GA 30333, USASearch for more papers by this author & Irene HallDivision of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention (NCHHSTP), Centers for Disease Control & Prevention (CDC), Mailstop D-21, 1600 Clifton Rd, Atlanta, GA 30333, USASearch for more papers by this authorPublished Online:31 May 2013https://doi.org/10.2217/fvl.13.35AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: HIVsurveillancetestingundiagnosedIn the USA, approximately 18% of the estimated 1.1 million individuals with HIV infection are unaware of their status, although the proportion has decreased somewhat in recent years [101]. HIV testing strategies for reaching the undiagnosed are showing promise, yet a key challenge is that accurate estimates of the proportion of infected individuals remaining undiagnosed are hard to obtain: multiple methods have been used, yet no consensus exists as to the best approach [1]. In order to reduce the proportion of undiagnosed infections, we need to both apply effective testing strategies and identify the best methods for estimation.Reaching and testing individuals unaware of their infection are critical to the success of HIV prevention in the USA. An estimated 49% of transmissions are from individuals living with HIV unaware of their infection [2]. Individuals with an undiagnosed HIV infection are more likely to transmit the virus to others, since they are more likely to be in the acute infection stage, with a higher infectiousness, and are less likely to take precautions than those who are aware of their status [3,4]. Identifying HIV infection at an early stage among all individuals – not just those with acute HIV infection – is critical for timely linkage to care, initiation of combination antiretroviral therapy when indicated and promotion of adherence to these regimens to reduce morbidity and transmission [5,6].Multiple HIV testing strategies are designed to reduce the number of undiagnosed infections. These include test and treat, routine testing and increased frequency of testing. Early diagnosis and prompt treatment are the basis for a ‘test-and-treat’ approach to reduce HIV transmission. Test-and-treat programs are characterized by aggressive methods to test a broad segment of a population in order to identify the undiagnosed and re-engage HIV-infected individuals in care. Early treatment improves overall health outcomes [7]. In addition, the reduced viral loads in individuals living with HIV who are on effective treatment greatly reduce the probability of transmission of the virus to others [8–10]. Individuals in care can also benefit from counseling for risk behaviors [102]. Community- and prison-based test-and-treat strategies are currently being evaluated for feasibility in the USA.Routine testing is another strategy for reaching the undiagnosed, and is particularly effective in areas with high prevalence for multiple reasons. People who may not seek out testing often accept it when offered. Providers may not assess HIV risk among all patients; routine testing takes away the need for risk assessment. Routine testing also reduces the stigma associated with HIV testing; when all patients are offered testing, no individual or group is singled out. Routine HIV testing is cost-effective in populations with undiagnosed HIV prevalence over 0.1% [11]. Recently, the United States Preventive Services Task Force (USPSTF) issued a recommendation that “clinicians screen adolescents and adults ages 15–65 years for HIV infection” [12]. This was a grade A recommendation. Grade A and B recommendations from the USPSTF are the basis for certain expansions of no-cost-sharing coverage for clinical preventive services under the Patient Protection and Affordable Care Act of 2010. This means that, for many insured individuals, routine HIV testing may be covered by health insurance plans or policies. CDC has implemented routine HIV testing through the Expanded HIV Testing Initiative in 30 public health jurisdictions; in the first 3 years of this program, 2.8 million tests were conducted and more than 18,000 individuals were newly diagnosed with HIV infection [13].In populations with high HIV incidence, frequent testing may be needed to stay abreast of undiagnosed infections. Men who have sex with men (MSM) account for the largest proportion (63%) of new HIV infections in the USA [103]. CDC guidelines identify MSM who should be tested more frequently according to their risk behaviors [11]. An analysis of a community-based sample of MSM in cities with high HIV and AIDS prevalence found that risk behaviors did not differentiate those newly diagnosed, and that frequent testing, perhaps as often as every 3–6 months, might be warranted among sexually active MSM to better identify undiagnosed infection [14]. CDC is currently funding two large-scale testing programs for MSM: one focusing on young MSM of color and the other focusing on African–American and Hispanic/Latino MSM of any age; these programs will provide model practices for reaching the undiagnosed in these subgroups.Improved sensitivity of HIV diagnostic tests also factor into strategies for identifying those with undiagnosed infections. The fourth-generation combined antigen/antibody test identifies infections early [4]. Tests that identify infection early allow for referral to early and appropriate care to improve health outcomes, and can be used to stop chains of transmission.Estimating the prevalence and characteristics of people with undiagnosed HIV infection at the national and local levels is critical to plan both routine and targeted testing programs; application of testing strategies should be informed by the best available data to characterize undiagnosed infections. Different methods of measuring undiagnosed HIV infection result in different estimates of the proportion undiagnosed; as noted above, there is no consensus on which method is best, and use of different methods may depend on available data [1]. Estimates of undiagnosed HIV infection in the USA have been derived from two surveillance systems: the National HIV Surveillance System (NHSS), which uses HIV case reports and modeling methods for estimation; and the National HIV Behavioral Surveillance System (NHBS), which estimates undiagnosed infections from prevalence surveys.Using NHSS data on HIV and AIDS diagnoses and deaths among individuals with HIV, the prevalence of diagnosed and undiagnosed HIV infections is estimated with a back-calculation method [15]. First, data are statistically adjusted to mitigate the effects of delays in reporting new cases and deaths, incomplete reporting of diagnosed cases and cases reported without sufficient risk factor information to be classified into an HIV transmission category. Second, on the basis of the estimated annual number of HIV diagnoses and the severity of disease at diagnosis (i.e., whether the infection was classified as stage 3 [AIDS] in the same calendar year the HIV diagnosis was made), the extended back-calculation model is fitted to estimate the cumulative number of individuals who had been infected with HIV each year. The estimated overall HIV prevalence is calculated by subtracting the estimated cumulative number of deaths that have occurred among those infected from the estimated cumulative number of HIV infections. The prevalence of undiagnosed HIV infection is calculated by subtracting the estimated number of diagnosed HIV infections in living individuals from the estimated overall HIV prevalence.This method of estimation using NHSS data serves as the metric for estimating the proportion of individuals with an undiagnosed HIV infection as an indicator for the National HIV/AIDS Strategy (NHAS). The NHAS goal is to increase the proportion of individuals who know their status to 90% by 2015 [104]. Current estimates based on the most recently published surveillance data for 2009 are that 18.1% remain undiagnosed [101].Another method used to describe undiagnosed infections is based on self-reported HIV status and subsequent HIV testing (i.e., prevalence surveys). In the USA, this latter method is available from NHBS.NHBS operates in 20 cities in the USA, with high rates of HIV and AIDS diagnoses. It is used to monitor prevalence and trends in risk behaviors, testing and use of prevention services among populations at high risk for acquiring HIV. Surveys and tests are offered without regard to self-reported HIV status. The percentage of individuals unaware of their HIV infection is defined as those newly diagnosed through NHBS who reported their HIV status as negative, indeterminate or unknown, or who reported never having an HIV test [14]. NHBS has produced estimates of undiagnosed infections of approximately 45% for MSM, injection drug users and heterosexuals [16].It is important to distinguish between NHSS and NHBS measures of undiagnosed infection and use them correctly (i.e., not using NHBS data to monitor progress towards NHAS goals, which are based on NHSS methods). Each method has strengths and limitations: for example, the NHBS method is subject to biases inherent in self-reported data and is designed to provide information on high-risk populations; the NHSS models, while appropriate to generalize to the US population, are based on a number of assumptions. Understanding the unique contributions of each method and how they might be used together (e.g., to describe undiagnosed infection among MSM) will help to create a better description of undiagnosed HIV infection in the USA.Reducing the proportion of individuals with an undiagnosed HIV infection is critical for improving health outcomes and reducing HIV transmission, addressing two of the goals of the NHAS. Testing programs are key to reducing the proportion of HIV-infected individuals who are undiagnosed. Addressing measurement issues in estimating the proportion who are undiagnosed is important to efficiently target resources and accurately assess progress. Continued development of methods for estimating this proportion and reaching those individuals with HIV testing and linkage to care are necessary for successful reductions in HIV infections in the USA.DisclaimerThe findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views of CDC.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Working Group on Estimation of HIV Prevalence in Europe. HIV in hiding: methods and data requirements for the estimation of the number of people living with undiagnosed HIV. AIDS25,1017–1023 (2011).Crossref, Medline, Google Scholar2 Hall HI, Holtgrave DR, Maulsby C. HIV transmission rates from persons living with HIV who are aware and unaware of their infection. AIDS26,893–896 (2012).Crossref, Medline, Google Scholar3 Branson BM, Stekler JD. Detection of acute HIV infection: we can’t close the window. J. Inf. Dis.205,521–524 (2012).Crossref, Medline, Google Scholar4 Marks G, Crepaz N, Janssen RS. Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA. AIDS20,1447–1450 (2006).Crossref, Medline, Google Scholar5 Mayer K.H. Introduction: linkage, engagement and retention in HIV care – essential for optimal individual- and community level outcomes in the era of highly active antiretroviral therapy. Clin. Infect. Dis.52,S205–S207 (2011).Crossref, Medline, Google Scholar6 Cheever LW. Engaging HIV-infected patients in care: their lives depend on it. Clin. Infect. Dis.44,1500–1502 (2007).Crossref, Medline, Google Scholar7 Le T, Wright EJ, Smith DM et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N. Engl. J. Med.368,218–230 (2013).Crossref, Medline, CAS, Google Scholar8 Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med.365,493–505 (2011).Crossref, Medline, CAS, Google Scholar9 Donnell D, Baeten JM, Kiarie J et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet375,2092–2098 (2010).Crossref, Medline, Google Scholar10 Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet373(9657),48–57 (2009).Crossref, Medline, Google Scholar11 Branson BM, Handsfield HH, Lampe MA; CDC. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm. Rep.55(RR-14),1–17 (2006).Medline, Google Scholar12 Moyer VA. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann. Intern. Med.156(12),880–891 (2012).Crossref, Medline, Google Scholar13 CDC. Results of the Expanded HIV Testing Initiative – 25 jurisdictions, United States, 2007–2010. MMWR Morb. Mortal. Wkly Rep.60(24),805–810 (2011).Medline, Google Scholar14 CDC. Prevalence and awareness of HIV infection among men who have sex with men – 21 cities, United States, 2008. MMWR Morb. Mortal. Wkly Rep.59(37),1201–1207 (2010).Medline, Google Scholar15 Hall HI, Song R, Rhodes P et al. Estimation of HIV incidence in the United States. JAMA300,520–529 (2008).Crossref, Medline, CAS, Google Scholar16 Oster AM, Finlayson T, Sionean C et al. Monitoring HIV risk: findings from the National HIV Behavioral Surveillance System, 2008–2010. Presented at: National HIV Prevention Conference. Atlanta, GA, USA, 15–17 August 2011.Google Scholar101 CDC. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data – United States and 6 U.S. dependent areas – 2010. HIV Surveillance Supplemental Report, Volume 17, Number 3 (Part A) (2012). www.cdc.gov/hiv/pdf/statistics_2010_HIV_Surveillance_Report_vol_17_no_3.pdf (Accessed 2 January 2013)Google Scholar102 CDC. Prevention with Persons with HIV. www.cdc.gov/hiv/pwp (Accessed 26 February 2013)Google Scholar103 CDC. Estimated HIV incidence in the United States, 2007–2010. HIV Surveillance Supplemental Report 17(4) (2012). http://www.cdc.gov/hiv/pdf/statistics_hssr_vol_17_no_4.pdf (Accessed 2 January 2013)Google Scholar104 White House Office of National AIDS Policy. National HIV/AIDS Strategy for the United States. The White House, Washington, DC, USA (2010). www.whitehouse.gov/ONAP (Accessed 2 January 2013)Google ScholarFiguresReferencesRelatedDetailsCited ByAn Adaptive Approach to Locating Mobile HIV Testing Services12 July 2017 | Medical Decision Making, Vol. 38, No. 2Scaling up Routine HIV Testing at Specialty ClinicsJAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 64, No. Supplement 1 Vol. 8, No. 6 Follow us on social media for the latest updates Metrics History Published online 31 May 2013 Published in print June 2013 Information© Future Medicine LtdKeywordsHIVsurveillancetestingundiagnosedDisclaimerThe findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views of CDC.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download