Branson, Bernard M. MD*; Viall, Abigail MA*; Marum, Elizabeth PhD†
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.
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