In the era of effective antiretroviral treatment, HIV testing serves as the gateway to improved health and survival among persons with HIV infection and decreased transmission within communities.1 Persons with HIV reduce high-risk behaviors substantially after they become aware they are infected,2 and early initiation of antiretroviral therapy reduces both clinical progression of HIV disease and sexual transmission to uninfected partners.3 Models of treatment as prevention that have inspired optimism about the elimination of HIV transmission are predicated on annual voluntary testing with immediate antiviral therapy.4,5 However, optimal HIV testing strategies, and their feasibility, acceptability, and cost-effectiveness, have yet to be established.
Although the need to expand HIV testing now seems clear, coming to this perspective required substantial evolution in epidemiology, medicine, policy, politics, and technology. Soon after HIV was first identified, immunoassays for HIV antibody were developed and deployed to screen blood donations, and in developed countries, transfusion-associated transmissions were soon eliminated.6 However, uncertainty about the prognosis of a positive antibody test and the lack of effective therapy caused skepticism about the value of HIV testing outside the blood donor setting.7,8 At the first International AIDS Conference in 1985, protesters with posters chanted “No Test is Best.”9 For asymptomatic persons, testing was perceived as an adjunct to HIV counseling for reducing HIV risk behaviors; client-initiated voluntary counseling and testing (VCT) became the norm.10,11 In the United States, targeted HIV counseling and testing were recommended for persons at increased risk and diagnostic testing was recommended for persons with signs or symptoms of HIV.12 In many resource-limited countries, HIV testing was limited to screening of blood transfusions13 and to selected referral centers; testing was typically not available for persons with or without symptoms.14
INITIAL EXPANSION OF HIV TESTING
Three developments in the early to mid-1990s began to shift the HIV testing paradigm: accumulating evidence that HIV infection persisted in all persons with HIV antibody,15,16 demonstration that administering zidovudine (or nevirapine) during pregnancy could prevent mother-to-child transmission,17,18 and the introduction of simple, inexpensive rapid HIV tests that allowed decentralized testing without sophisticated laboratory equipment.19–21 Initiatives for prevention of mother-to-child transmission (which included voluntary testing of all pregnant women) extended HIV testing for the first time to populations not thought to be at increased risk.22 These efforts also stimulated studies of alternative approaches for HIV screening, including routine voluntary (opt-out) testing in prenatal clinics.23,24 The number of persons tested annually during this early expansion was not well documented in many countries, but surveys show that by 2001 in the United States, 52% of pregnant women reported an HIV test in the past 12 months.25 Although testing was extremely limited in Africa throughout the 1990s, this changed rapidly in the 2000s, particularly in the context of services for pregnant women. For example, in Kenya, Demographic and Health Surveys indicate the percentage of women reporting testing in the past 12 months increased from 6.7% in 2003 to 29.3% in 2008, and in Lesotho, from 6.3% in 2004 to 42.0% in 2009.26
Point-of-care rapid HIV tests quickly revolutionized HIV testing in resource-limited countries, and the use of 2 or more rapid tests for HIV diagnosis was endorsed by the World Health Organization and UNAIDS in 1998.27 In the developed world, however, various hurdles delayed adoption of rapid tests. Point-of-care rapid HIV tests first became available in the United States in 2002 and in Australia, not until 2012.28,29 Worldwide, rapid tests moved HIV testing from clinical laboratories to the point of care in health facilities with limited laboratory services and to community sites, including dedicated testing sites, religious facilities, schools, workplaces, transport hubs, and homes.30–32 Mobile services have used creative approaches to deliver HIV testing via vans, trucks, bicycles, and even camels. Notwithstanding, many persons with HIV remain undiagnosed. UNAIDS estimated in 2012 that globally only about 50% of persons living with HIV infection knew their HIV status33 compared with 82% in the United States by the end of 2009.34,35
IMPETUS FOR FURTHER SCALE-UP OF HIV TESTING
Three subsequent developments led to the current efforts to further scale-up HIV testing and case finding: access to antiretroviral therapy in resource-limited settings,36 increasing evidence that therapy is beneficial for asymptomatic HIV,33,37 and definitive evidence that antiretroviral therapy can prevent sexual transmission.3
In 2004, Botswana introduced routine, opt-out HIV testing; it was widely accepted and seemed to reduce barriers to testing.38 Lesotho followed in 2005, and in 2006, the US Centers for Disease Control and Prevention (CDC) recommended routine opt-out screening in health-care settings.39 CDC also launched an expanded HIV testing initiative to facilitate adoption of HIV screening in healthcare settings. From 2007 to 2010, health departments conducted nearly 2.8 million HIV tests under this initiative, of which 29,503 (1.1%) were positive.40 Among those who tested positive, 62% had been unaware of their HIV infection.
In 2007, World Health Organization issued guidelines recommending provider-initiated testing and counseling in countries with generalized epidemics, and many countries with high HIV burden began to expand HIV testing in the context of health services.41 For example, funds from President's Emergency Plan for AIDS Relief supported the provision of 1.9 million testing sessions in 2004; this increased to more than 46 million in 2012.26 However, the rapid expansion of testing services, the increasing reliance on lay testers, and the difficulty of providing supervision and quality assurance raised concerns about accuracy of test results.42 Although immediate, on-site confirmation from 2 or 3 different rapid tests remains the dominant model in most high-burden countries, concerns regarding quality have led a few countries to consider piloting alternatives, such as screening with only one test in community venues or homes, with referral to HIV care sites after a reactive rapid test result for confirmatory testing and immediate enrollment in care and treatment. Similar strategies have been adopted in the United States in an effort to facilitate entry into HIV care.43
With the mandate to scale-up testing, debate ensued between human rights advocates (who expressed concerns about privacy, confidentiality, counseling, and consent) and some clinicians and public health officials (who sought to normalize testing).44 The latter, asserting that routine HIV testing and case finding were essential to increase access to HIV treatment, feared that the exceptional procedures characteristic of the traditional VCT approach might actually perpetuate the stigma associated with HIV and HIV testing and so limit its availability and acceptability.45,46 Increasingly, calls appeared for application of traditional public health principles, such as named reporting, routine testing, and partner notification, to the HIV epidemic.47,48
The percentage of US adults who had ever been tested for HIV increased from 40% in 2006 to 45% in 2010, but the percentage of those who had been tested in the past 12 months remained unchanged at 10% from 2000 to 2010.49 Meanwhile, even though emergency departments have long been recognized as promising venues for reaching vulnerable populations disproportionately affected by HIV and for identifying previously undiagnosed HIV infections,50–52 only 1 in 5 emergency departments had a systematic HIV testing program in place in 200953 and few seem to conduct targeted testing based on documented risk factors.54 Paradoxically, despite enthusiasm for compulsory preoperative and preadmission testing early in the HIV epidemic,55–57 fewer than half of US hospitals surveyed in 2009 to 2010 intended to implement CDC's recommendations to screen their patients for HIV.58 The Veterans Administration Health System is a notable exception: the number of unique patients who had an HIV test in the calendar year increased by 268% after a directive was issued to offer HIV testing to all patients, from 142,000 in 2009 to 523,000 in 2011.59
NOVEL METHODS ON THE PATH TO UNIVERSAL TESTING
Kenya offers an informative example of how HIV testing has evolved.32 In 2000, the government of Kenya, faced with a generalized epidemic and estimated HIV prevalence of 9% in adults, made a commitment to the rapid extension of VCT services. National guidelines for VCT were developed by a committee composed of multiple stakeholders, including government officials, counselors, laboratory representatives, donors, and persons living with HIV. Simple, whole-blood rapid tests were adopted, which resulted in several unexpected benefits. Counselors reported that persons receiving VCT liked to see their own test strips and engage in interpretation of test results.32 This enhanced confidence in the test results, reduced waiting time, virtually eliminated loss to follow-up for confirmed test results, and decreased the potential for clerical errors. In 2000, 3 sites provided VCT services to approximately 1100 persons in Kenya. By 2005, 680 VCT sites (75% of which were in health-care facilities) provided HIV tests to 545,000 persons.32
Emphasis on diagnostic testing was also needed to achieve Kenya's treatment targets. Testing in rural areas remained limited, and self-initiated VCT was not ideal for identifying large numbers of persons with advanced HIV infection. Consequently, the Kenya Ministry of Health issued new guidelines in 2004 for HIV testing in clinical settings.60 These outlined definitions and standards for routine and diagnostic testing and advocated an opt-out approach for testing in antenatal clinics, tuberculosis clinics, sexually transmitted infection services, and other clinical services. The prevalence of HIV among persons tested subsequently in health facilities ranged from 11% among women attending child health clinics to more than 70% among rural patients with tuberculosis.61,62 To reach their ambitious goal (80% of Kenyans knowing their HIV status by the year 2010), the government of Kenya also updated guidance for HIV testing and counseling that incorporates traditional VCT, testing in health facilities, community-based outreach testing, and innovations such as door-to-door HIV testing, self-testing, and couples and family testing.63
Couples testing and counseling have been provided in the context of research studies in Rwanda since 1987 and in Zambia since 1994 and has proven highly effective for identifying serodiscordant couples and assisting them with mutual disclosure and follow-up services.64 Reminiscent of the experience with rapid test adoption, couples testing is now gaining attention in the United States after its widespread implementation in Africa.65 However, fear of adverse consequences for the HIV-positive member of the couple discourages many couples from accepting couples testing and counseling, and the proportion of people who know both their own status and that of their sexual partner(s) remains low, both in the United States and elsewhere.
By removing distance as a barrier, home-based testing might be an effective out-of-facility approach for identifying HIV-infected people at an earlier stage of their disease. In door-to-door home-based testing, the test provider approaches the client regardless of his or her perceived risk of having HIV. In an analysis of studies of more than 500,000 people who were offered home-based testing in Africa, the proportion who accepted ranged from 59.1% to 99.7%; of those tested, 99.6% received their test result.66 Acceptance was highest among persons who had not tested previously. Qualitative research found that the most common reasons for the popularity of home-based testing were fear of stigmatization and emotional vulnerability associated with receiving results from public facilities.
Self-testing offers another new opportunity to expand HIV testing. In the United States, home sample collection for HIV testing has been available since 1996. Home collection users obtain a dried blood spot sample, mail it to a laboratory, and telephone to receive their test results. When home collection kits were first introduced, 0.9% of users tested positive; nearly 60% of users, and 49% of those who tested positive, had never been tested before.67 In July 2012, a true rapid HIV self-test—one that persons perform themselves on oral fluid—was approved by the US Food and Drug Administration. The self-test might facilitate testing among persons who have not been tested before and promote more frequent testing by persons with ongoing risk behaviors. In the hands of home users, the sensitivity of the rapid self-test was 91.67% and specificity was 99.98%.68 Participants in initial studies found the test very easy to use, and most performed the test without mistake while being observed.69 In Malawi, 92% of 283 study participants elected an oral fluid self-test after a demonstration. Overall accuracy was 99.2% (2 of 48 participants with positive finger-stick blood rapid tests obtained negative oral fluid self-test results).70 In a study of oral fluid self-testing in Singapore, 977 (99.1%) participants obtained correct results and more than 80% said they would purchase a self-test.71 Self-testing may have considerable potential for regular re-testing of persons engaged in high-risk behaviors for whom retesting is recommended annually.39,72 Especially in high-burden countries, with large numbers of persons who have never tested and shortages of health manpower, encouraging people with on-going risk who have been tested previously to use self-tests might help achieve the regular testing needed to identify persons early in infection.
The “test and treat” approach for prevention entails expanded testing to identify all persons with HIV as early in the course of their infection as possible. Testing expansion depends on routinizing HIV testing, which in turn, must take full advantage of all the testing modalities now available while reducing stigma, assuring accuracy, maintaining quality, and controlling costs. Achieving broad coverage will require expanded testing in health facilities, traditional VCT sites, community settings including the home, and self-testing, all in the context of respect for autonomy and the highest standards of confidentiality. Treatment and care must be available, and post-test counseling must include linkage to HIV care and support for persons who test positive to notify their sex partners, either through couples VCT (where both partners learn their results together), disclosure in a medical setting (ideally with both partners together), or through partner notification.
The future of HIV testing is changing. Lessons from the eradication of smallpox might prove illuminating, despite the many differences between the 2 diseases. In the 1960s and 1970s, eradication efforts were initially dominated by an emphasis on mass vaccination, which proved impossible to achieve. A different, and at the time controversial, approach ultimately proved to be the key to success—intensive case finding, with immediate vaccination of all household members of identified patients. A similar shift in emphasis toward case finding might be as important for HIV elimination as it was for smallpox eradication. In the words of Foege,72 this controversial approach “proved itself ideally suited for eradicating a virus that had eluded the best efforts of mass vaccination programs for 175 years.” Absent a vaccine, case finding and treatment hold the most promise for the control of HIV.
2. Marks G, Crepaz N, Senterfitt JW, et al.. 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;39:446–452.
3. Cohen MS, Chen YQ, McCauley M, et al.. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505.
4. Granich RM, Gilks CF, Dye C, et al., . Universal voluntary HIV testing
with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009;373:48–57.
5. Ruark A, Shelton JD, Halperin DT, et al., . Universal voluntary HIV testing
and immediate antiretroviral therapy. Lancet. 2009;373:1078; author reply 1080–1071.
6. Lackritz EM, Satten GA, Aberle-Grasse J, et al.. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med. 1995;333:1721–1725.
7. Meyer KB, Pauker SG. Screening for HIV: can we afford the false positive rate? N Engl J Med. 1987;317:238–241.
8. Rhame FS, Maki DG. The case for wider use of testing for HIV infection. N Engl J Med. 1989;320:1248–1254.
9. Piot P. No Time to Lose: A Life in Pursuit of Deadly Viruses. New York, NY: W.W. Norton & Co; 2012.
10. Higgins DL, Galavotti C, O'Reilly KR, et al.. Evidence for the effects of HIV antibody counseling and testing on risk behaviors. JAMA. 1991;266:2419–2429.
11. Doll LS, Kennedy MB. HIV counseling and testing: what is it and how well does it work? In: Schochetman G, George JR, eds. AIDS Testing: A Comprehensive Guide to Technical, Medical, Social, Legal, and Management Issues. 2nd ed. New York, NY: Springer-Verlag;1994:302–319.
12. CDC. Public Health Service guidelines for counseling and antibody testing to prevent HIV infection and AIDS. MMWR Morb Mortal Wkly Rep. 1987;36:509–515.
13. Lackritz EM. Prevention of HIV transmission by blood transfusion in the developing world: achievements and continuing challenges. AIDS. 1998;12(suppl A):S81–S86.
14. deCock KM, Mbori-Ngacha D, Marum E. Shadow on the continent: public health and HIV/AIDS in Africa in the 21st century. Lancet. 2006;360:67–72.
15. Rutherford GW, Lifson AR, Hessol NA, et al.. Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11 year follow up study. BMJ. 1990;301:1183–1188.
16. Hearst N, Hulley SB. Preventing the heterosexual spread of AIDS. Are we giving our patients the best advice? JAMA. 1988;259:2428–2432.
17. Connor EM, Sperling RS, Gelber R, et al.. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994;331:1173–1180.
18. Downing R, Otten R, Marum E. Optimizing the delivery of HIV counseling and testing services: the Uganda experience using rapid HIV antibody test algorithms. J Acquir Immune Defic Syndr. 1998;18:384–388.
19. Kassler W, Alwano-Edyegu M, Marum E. Rapid HIV testing
with same-day results: a field trial in Uganda. Int J STD AIDS. 1998;9:134–138.
20. Kassler W, Dillon B, Haley C. On-site, rapid HIV testing
with same-day results and counseling. AIDS. 1997;11:1045–1051.
21. CDC. U.S. Public Health Service recommendations for human immunodeficiency virus counseling and voluntary testing for pregnant women. MMWR Recomm Rep. 1995;44:1–15.
22. Cartoux M, Meda N, Van de Perre P, et al.. Acceptability of voluntary HIV testing
by pregnant women in developing countries: an international survey. Ghent International Working Group on Mother-to-Child Transmission of HIV. AIDS. 1998;12:2489–2493.
23. Simpson WM, Johnstone FD, Goldberg DJ, et al.. Antenatal HIV testing
: assessment of a routine voluntary approach. BMJ. 1999;318:1660–1661.
24. Anderson JE, Santelli J, Mugalla C. Changes in HIV-related preventive behavior in the US population: data from national surveys, 1987-2002. J Acquir Immune Defic Syndr. 2003;34:195–202.
25. Marum E, Taegtmeyer M, Parekh B, et al.. "What took you so long?" The impact of PEPFAR on the expansion of HIV testing
and counseling services in Africa. J Acquir Immune Defic Syndr. 2012;60(suppl 3):S63–S69.
26. WHO, UNAIDS. The importance of simple/rapid assays in HIV testing
. Wkly Epidemiol Rec. 1998;73:321–328.
27. CDC. Approval of a new rapid test for HIV antibody. MMWR Morb Mortal Wkly Rep. 2002;51:1051–1052.
29. McKenna SL, Muyinda GK, Roth D, et al.. Rapid HIV testing
and counseling for voluntary testing centers in Africa. AIDS. 1997;11(suppl 1):S103–S110.
30. Grabbe KL, Menzies N, Taegtmeyer M, et al.. Increasing access to HIV counseling and testing through mobile services in Kenya: strategies, utilization, and cost-effectiveness. J Acquir Immune Defic Syndr. 2010;54:317–323.
31. Marum E, Taegtmeyer M, Chebet K. Scale-up of voluntary HIV counseling and testing in Kenya. JAMA. 2006;296:859–862.
32. Emery S, Neuhaus JA, Phillips AN, et al.. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008;197:1133–1144.
35. Stringer JS, Zulu I, Levy J, et al.. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006;296:782–793.
36. Hogan CM, Degruttola V, Sun X, et al.. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals. J Infect Dis. 2012;205:87–96.
37. Weiser SD, Heisler M, Leiter K, et al.. Routine HIV testing
in Botswana: a population-based study on attitudes, practices, and human rights concerns. PLoS Med. 2006;3:e261.
38. 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;55:1–17.
39. CDC. Results of the expanded HIV testing
initiative–25 jurisdictions, United States, 2007-2010. MMWR Morb Mortal Wkly Rep. 2011;60:805–810.
41. Shanks L, Klarkowski D, O'Brien DP. False positive HIV diagnoses in resource limited settings: operational lessons learned for HIV programmes. PLoS One. 2013;8:e59906.
43. Tarantola D, Gruskin S. New guidance on recommended HIV testing
and counselling. Lancet. 2007;370:202–203.
44. World Health Organization. Increasing access to knowledge of HIV status: conclusions of a WHO consultation, December 3–4, 2001. Available at: www.who.int/hiv/pub/vct/pub16/en/index.html
. Accessed February 12, 2013.
45. Bayer R, Edington C. HIV testing
, human rights, and global AIDS policy
: exceptionalism and its discontents. J Health Polit Policy
46. Frieden TR, Das-Douglas M, Kellerman SE, et al.. Applying public health principles to the HIV epidemic. N Engl J Med. 2005;353:2397–2402.
47. Manavi K, Welsby PD. HIV testing
. BMJ. 2005;330:492–493.
49. Lyss SB, Branson BM, Kroc KA, et al.. Detecting unsuspected HIV infection with a rapid whole-blood HIV test in an urban emergency department. J Acquir Immune Defic Syndr. 2007;44:435–442.
50. White DA, Scribner AN, Schulden JD, et al.. Results of a rapid HIV screening and diagnostic testing program in an urban emergency department. Ann Emerg Med. 2009;54:56–64.
51. Sattin RW, Wilde JA, Freeman AE, et al.. Rapid HIV testing
in a southeastern emergency department serving a semiurban-semirural adolescent and adult population. Ann Emerg Med. 2011;58(suppl 1):S60–S64.
52. Rothman RE, Hsieh YH, Harvey L, et al.. 2009 US emergency department HIV testing
practices. Ann Emerg Med. 2011;58(suppl 1):S3–S9e1–e4.
53. Hoover JB, Tao G, Heffelfinger JD. Monitoring HIV testing
at visits to emergency departments in the United States: very-low rate of HIV testing
. J Acquir Immune Defic Syndr. 2013;62:90–94.
54. Cleary PD, Barry MJ, Mayer KH, et al.. Compulsory premarital screening for the human immunodeficiency virus. Technical and public health considerations. JAMA. 1987;258:1757–1762.
55. Meadows J, Irving G, Chapman K, et al.. Preoperative HIV antibody testing: the views of surgeons and patients. Int J STD AIDS. 1995;6:426–430.
56. Gordin FM, Gibert C, Hawley HP, et al.. Prevalence of human immunodeficiency virus and hepatitis B virus in unselected hospital admissions: implications for mandatory testing and universal precautions. J Infect Dis. 1990;161:14–17.
57. Voetsch AC, Heffelfinger JD, Yonek J, et al.. HIV screening practices in U.S. hospitals, 2009-2010. Public Health Rep. 2012;127:524–531.
58. Czarnogorski M, Halloran J, Pedati C, et al.. Expanded HIV testing
in the United States Department of Veterans Affairs, 2009 to 2011. Am J Public Health. In press.
59. National AIDS and STD Control Programme. Guidelines for HIV Testing
in Clinical Settings. Nariobi, Kenya: Ministry of Health, Republic of Kenya; 2004.
60. Chersich MF, Luchters SM, Othigo MJ, et al.. HIV testing
and counselling for women attending child health clinics: an opportunity for entry to prevent mother-to-child transmission and HIV treatment. Int J STD AIDS. 2008;19:42–46.
61. Huerga H, Spillane H, Guerrero W, et al.. Impact of introducing human immunodeficiency virus testing, treatment and care in a tuberculosis clinic in rural Kenya. Int J Tuberc Lung Dis. 2010;14:611–615.
63. Kelley AL, Karita E, Sullivan PS, et al.. Knowledge and perceptions of couples' voluntary counseling and testing in urban Rwanda and Zambia: a cross-sectional household survey. PLoS One. 2011;6:e19573.
64. Wagenaar BH, Christiansen-Lindquist L, Khosropour C, et al.. Willingness of US men who have sex with men (MSM) to participate in Couples HIV Voluntary Counseling and Testing (CVCT). PLoS One. 2012;7:e42953.
65. Sabapathy K, Van den Bergh R, Fidler S, et al.. Uptake of home-based voluntary HIV testing
in sub-Saharan Africa: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001351.
66. Branson BM. Home sample collection tests for HIV infection. JAMA. 1998;280:1699–1701.
67. Myers JE, El-Sadr WM, Zerbe A, et al.. Rapid HIV self-testing: long in coming but opportunities beckon. AIDS. 2013;27. [Epub ahead of print] DOI: 10.1097/QAD.0b013e32835fd7a0.
68. Carballo-Dieguez A, Frasca T, Dolezal C, et al.. Will gay and bisexually active men at high risk of infection use over-the-counter rapid HIV tests to screen sexual partners? J Sex Res. 2012;49:379–387.
69. Choko AT, Desmond N, Webb EL, et al.. The uptake and accuracy of oral kits for HIV self-testing in high HIV prevalence setting: a cross-sectional feasibility study in Blantyre, Malawi. PLoS Med. 2011;8:e1001102.
70. Ng OT, Chow A, Lee V, et al.. Accuracy and user-acceptability of HIV self-testing using an oral fluid HIV rapid test [Abstract 1075]. 18th Conference on Retroviruses and Opportunistic Infections; 2011; Boston, Massachusetts.
72. Foege W. House on Fire: The Fight to Eradicate Smallpox. Berkely, CA: University of California Press; 2011.