The Holy Grail: the search for undiagnosed cases is paramount in improving the cascade of care among people living with HIV.

Eyawo, Oghenowede ; Hogg, Robert S. ; Montaner, Julio S.G. 等

Highly Active Antiretroviral Therapy (HAART) has transformed the nature of HIV/AIDS from an imminent death sentence to a chronic manageable condition. (1,2) Although the research community has yet to celebrate a breakthrough in the development of a vaccine for HIV, considerable progress has been made since the introduction of HAART in 1996. There is sound evidence that HAART is effective in reducing HIV/AIDS-related morbidity and mortality among HIV-positive individuals receiving these therapies. (3,4) The past few years have witnessed a growing interest in the potential impact of "treatment as prevention" based on the notion that expanded coverage with HAART would substantially reduce HIV and AIDS-related morbidity and mortality and secondarily HIV transmission. (5) The recent news that an HIV-infected infant treated with early HAART has achieved a "functional cure"--where the HIV viral load is suppressed to undetectable levels and the virus is no longer replicating (6)--is an exciting development. Similarly, findings from a French cohort showed that very early treatment among HIV-infected adults could lead at least in some instances to a "functional cure". (7)

However, it is estimated that in North America, somewhere around 20% of HIV-infected persons remain undiagnosed. (8,9) This represents a huge challenge and a missed opportunity. Undiagnosed HIV cases cannot benefit from HAART and are more likely to experience HIV-related morbidity and untimely mortality. Furthermore, HIV-undiagnosed individuals unknowingly contribute disproportionately to onwards transmission, in part due to the higher prevalence of high-risk sexual behaviour compared to their HIV-diagnosed counterparts. (10) As such, they pose a major threat to the control of the spread of HIV in terms of their continuing transmission of the disease to the community. Current surveillance estimates of people living with HIV/AIDS do not accurately reflect the number of all IV-infected individuals, primarily because not all infected individuals have been tested. As a result, these undocumented and mostly asymptomatic individuals are unaware of their infection and thus they are not able to enter into care in a timely fashion; this leads to an excess risk for morbidity and mortality, and an inability to take adequate preventive measures, which in due course makes these individuals more likely to transmit the infection. (10) Naturally, preventive strategies and programs targeting HIV-positive individuals fail to reach this critical group, with serious consequences. In the United States, 207,600 (18.1%) of the estimated 1.1 million individuals living with HIV in 2009 were believed to be unaware of their positive status. (8) In Canada, an estimated 17,980 (25.2%) of the estimated 71,300 persons living with HIV as at the end of 2011 were unaware of their HIV infection. (9) In the United Kingdom, the same was true for an estimated 22,600 (24%) of the estimated 96,000 people living with HIV as of 2011. (11)

Effective strategies to promote early detection of HIV are urgently required. Considering that barriers to testing exist at several levels--including at the individual, health care provider and institutional levels--strategies to improve testing should incorporate approaches where HIV testing is both provider--and non-provider-initiated. These include offering routine testing at the time of acute care admissions and emergency department visits, increased screening campaigns and the possible use of home test kits. Additionally, HIV screening at the point of care should be much more ubiquitous, including taking place at methadone clinics, STI clinics, pharmacies, and dentist offices. Indeed, a recent HIV screening and testing guide produced by the Public Health Agency of Canada recommends discussing and considering HIV testing as a part of periodic routine medical care. (12) In addition to these, active engagement of sex workers to encourage their clients to seek testing also needs to be promoted. A number of these initiatives are being undertaken in the province of British Columbia, Canada, which has recently expanded the STOP HIV/AIDS ("Seek and Treat for Optimal Prevention of HIV/AIDS") pilot project to the rest of the province, as a means to further decrease HIV-related morbidity and mortality and, secondarily, new HIV infections. (13,14) The STOP HIV/AIDS initiative represents a strategy to promote early HIV diagnosis to facilitate and support immediate and sustained involvement with HIV/AIDS health-related services among HIV-positive individuals in order to optimize their engagement with the cascade of care. (15,16)

The expanding nature of the HIV pandemic presents extraordinary challenges for global health, human and international development, and economic growth. Efforts to curb the advance of the pandemic are fraught with challenges, including the absence of free and universal access to HAART worldwide, and the lack of a cure and a vaccine. While these challenges persist, we propose that undiagnosed HIV cases represent the biggest challenge yet in the fight against HIV/AIDS. Therefore, identifying them should be a priority and a critical focal point of HIV prevention programs. Timely diagnosis of HIV-infected individuals can provide opportunities for early linkage to and retention in care, as well as access to other preventive health care services. To successfully achieve the goals of HIV scale-up preventive efforts, strategies to promote increased HIV testing, early detection and engagement in care need to be increased and actively pursued. "The Holy Grail", or early identification and linkage to care of undiagnosed cases, is therefore paramount in improving the cascade of care among people living with HIV. Until this is achieved, the prospect of a significant reduction in the continuing high rates of disease transmission of HIV remains uncertain.

REFERENCES

(1.) Nokes KM. Revisiting how the Chronic Illness Trajectory Framework can be applied for persons living with HIV/AIDS. Sch Inq Nurs Pract 1998; 12(1): 27-31.

(2.) World Health Organization. HIV/AIDS in Europe--Moving from death sentence to chronic disease management. Matic S, Lazarus J, Donoghoe MC (Eds.), WHO Regional Office for Europe, 2006.

(3.) Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d'Arminio Monforte A, et al. Decline in the AIDS and death rates in the EuroSIDA study: An observational study. Lancet 2003; 362(9377): 22-29.

(4.) Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338(13): 853-60.

(5.) Montaner JS, Hogg RS, Wood E, Kerr T, Tyndall M, Levy AR, et al. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet 2006; 368(9534): 531-36.

(6.) Persaud D, Gay H, Ziemniak C, Chen YH, Piatek M, Chun T-W, et al. (Eds.). Functional HIV cure after very early ART on an infected infant. 20th Conference on Retroviruses and Opportunistic Infections (CROI), Abstract # 48LB. Atlanta, GA: March 4, 2013.

(7.) Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 2013; 9(3): e1003211.

(8.) Centers for Disease Control and Prevention. 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 2012; 17(3, part A).

(9.) Public Health Agency of Canada. Summary: Estimates of HIV Prevalence and Incidence in Canada, 20ll. Available at: http://www.phac-aspc.gc.ca/aidssida/ publication/survreport/estimat2011-eng.php (Accessed March 20, 2013).

(10.) Marks G, Crepaz N, Senterfitt JW, Janssen RS. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: Implications for HIV prevention programs. J Acquir Immune Defic Syndr 2005; 39(4): 446-53.

(11.) Health Protection Agency. HIV in the United Kingdom: 2012 Report. Department of Health, Social Services and Public Safety, 2012. Available at: http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/1211HIV intheUK2012/ (Accessed March 20, 2013).

(12.) Public Health Agency of Canada. Human Immunodeficiency Virus: HIV Screening and Testing Guide. 2012. Available at: http://www.catie.ca/sites/ default/files/EN_HIV-Screening-Guide-2013.pdf (Accessed September 6, 2013).

(13.) STOP HIV/AIDS Collaborative Pilot Project. STOP HIV/AIDS--Seek and Treat for Optimal Prevention of HIV/AIDS pilot project. 2012. Available at: http://www.stophivaids.ca/stop-hivaids-pilot-project (Accessed March 31, 2013).

(14.) British Columbia Centre for Excellence in HIV/AIDS. STOP HIV/AIDS. 2012. Available at: http://cfenet.ubc.ca/stop-hiv-aids/about (Accessed March 31, 2013).

(15.) Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis 2011; 52(6): 793-800.

(16.) Nosyk B, Montaner JS, Colley G, Lima VD, Chan K, Heath K, et al. The cascade of HIV care in British Columbia, Canada, 1996-2011: A population-based retrospective cohort study. Lancet Infect Dis 2013; doi:pii: S14733099(13)70254- 58. [Epub ahead of print]

Received: May 17, 2013

Accepted: September 26, 2013

Oghenowede Eyawo, MPH, (1,2) Robert S. Hogg, PhD, (1,2) Julio S.G. Montaner, MD (2,3)

Author Affiliations

(1.) Faculty of Health Sciences, Simon Fraser University, Vancouver, BC

(2.) British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC

(3.) Faculty of Medicine, University of British Columbia, Vancouver, BC

Correspondence: Dr. Julio S.G. Montaner, BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Tel: 604-806-8477, Fax: 604-806- 9044, E-mail: [email protected]

Acknowledgements of sources of support: Oghenowede Eyawo is supported by a Canadian Institutes of Health Research (CIHR) Doctoral Award. Dr. Robert Hogg has held grant funding in the last five years from the National Institutes of Health, CIHR, Health Canada, Merck, and the Social Sciences and Humanities Research Council of Canada. Dr. Hogg is a member of the STOP HIV/AIDS Study Group. Dr. Julio Montaner is supported by the British Columbia Ministry of Health and through an Avant-Garde Award (No. 1DP1DA026182) from the National Institute of Drug Abuse (NIDA), at the US National Institutes of Health (NIH). He has also received financial support from the International AIDS Society, United Nations AIDS Program, World Health Organization, National Institutes of Health Research-Office of AIDS Research, National Institute of Allergy & Infectious Diseases, The United States President's Emergency Plan for AIDS Relief (PEPfAR), UNICEF, the University of British Columbia, Simon Fraser University, Providence Health Care and Vancouver Coastal Health Authority. He has received grants from Abbott, Boehringer-Ingelheim, Bristol- Myers Squibb, Gilead Sciences, Janssen, Merck and ViiV Healthcare; Dr. Montaner is a member of the STOP HIV/AIDS Study Group.

Conflict of Interest: None to declare.