Challenges and Failures of HIV Screening With Rapid Tests

Introduction

Human Immunodeficiency Virus (HIV) is contracted through the exchange of blood, semen, vaginal secretions, or breast-milk from an infected individual. Eventually, HIV can lead to Acquired Immune Deficiency Syndrome (AIDS), which is a condition in which the infected individual’s immune system is severely compromised. (1) Today, practitioners, medical providers, and public health officials continue to search for new strategies to eliminate the global HIV/AIDS epidemic. It is estimated that 20 million people heave died from AIDS since it was first diagnosed in 1981, and there are roughly 40 million people living with HIV or AIDS worldwide today. Testing for HIV has become a critical component of HIV/AIDS prevention strategies due to the fact that an alarming number of the people afflicted with HIV remain unaware of their infection.(2)

The fairly recent development of rapid HIV testing is transforming the HIV screening process, enabling low-resource countries to test more people without the use of a laboratory or expensive equipment.  Due to lower costs and faster results, the use of rapid testing is especially practical for testing within mobile clinics and at community health screenings.(3) With this new technology, patients are able to receive their results just twenty to thirty minutes after being tested, rather than waiting weeks for results through traditional testing methods. Within the U.S. alone, it is estimated that approximately 25% of HIV-positive patients who are tested via traditional methods such as the ELISA test do not return for their results. Rapid testing virtually eliminates this problem, enabling more people to become immediately aware of their HIV status.(4) Theoretically, by making affordable testing available to more people and by increasing the likelihood that people will actually receive their results, rapid testing should have a considerably positive impact on public health prevention strategies to reduce and eventually eliminate HIV/AIDS transmission. However, the potential benefits of rapid HIV testing are not without drawbacks. Testing inaccuracies and ethical concerns draw attention to some of the more serious shortcomings of rapid testing.(5)

Efficacy of Rapid Testing

As HIV screenings become more widely required and more commonly conducted, the use of rapid tests is increasing.  A primary concern about rapid testing is the poor testing sensitivity and the unacceptably high rate of false positive results.  In the Rakai district of Southwestern Uganda, a region heavily plagued by HIV, trials conducted on the three most commonly used rapid HIV tests in Uganda revealed critical inaccuracies in rapid testing results. When the results of the rapid tests were retested using traditional tests that have been proven to be acceptably reliable, such as the western blot test and an enzyme immunoassay, it was discovered that 129 of the 295 people who were diagnosed as HIV-positive were actually HIV-negative.(6) Thus, nearly 45% of the patients who received positive results received them in error.  Although the rapid tests in question had reasonable sensitivities, averaging approximately 97.7%, the specificity ratings of the tests proved to be unacceptably low with an average specificity of 90.7%, causing the high frequency of false-positive results.(7) According to World Health Organization recommendations, HIV testing methods should have a sensitivity of at least 99% and a specificity of at least 98%.  This means that the test should give a positive result when the condition is present at least 99% of the time, and the test must also give a negative result at least 98% of the time when the patient does not have the condition. (8) According to these standards, the rapid HIV tests currently used by the Ugandan Ministry of Health do not meet the proposed criteria for sensitivity or specificity.

The alarmingly high frequency of false-positive results is not unique to Uganda. A recent study performed in the Eastern Democratic Republic of Congo found that two consecutive positive results from two separate rapid tests have a 10.5% chance of producing false-positive results.(9) Another study analyzed one of most popular rapid testing algorithms used in Cameroon, an algorithm which first tests with a rapid test called Determine and then confirms results with another rapid test called ImmunoCombII. The algorithm demonstrated a sensitivity of 100% but a specificity of only 91.5.%. Therefore, although this rapid testing combination produces virtually no false negatives, it regularly leads to false positive results.(10) A second commonly used testing algorithm employed by the Cameroonian Ministry of Health results in a specificity of 98.8%, which is significantly higher than that of the first testing combination. Yet despite the improvement in specificity, 2 out of every 100 people who are tested with this algorithm are still receiving false positive results. “2% false HIV positive individuals in a high burden country such as South Africa with more than 5 million HIV infections will correspond to about 100,000 people falsely declared HIV positive.”(11) Comparatively speaking, 98.8% is a relatively high specificity, one that meets the World Health Organization’s standards, yet hundreds of thousands of people are still being misdiagnosed as HIV-positive. Unfortunately, many countries are currently using rapid testing combinations in which the specificity is significantly lower that 98%, resulting in an even higher number of false positive diagnoses.

Further complicating the issue, some studies have revealed that certain types of rapid HIV tests are also producing false-negative results.  A study conducted by the South African government revealed rapid HIV testing sensitivities that averaged 68.7% in Cape Town’s local clinics.(12) Thus, the tests are failing to detect HIV in nearly one third of patients who have the virus. In Cameroon, the same rapid testing algorithm that produces a specificity of 98.8% has a sensitivity of 94.7%, resulting in 6 out of every 100 people receiving a negative diagnosis when they are in fact HIV-positive.(13) In the case of false negatives, the use of rapid testing to diagnose HIV during health fairs or screenings can actually do more harm than good by misleading an HIV-positive individual to believe that they are HIV-negative. False negatives are a threat not only to public health prevention strategy but also to the health and well being of the individual. A negative diagnosis, despite being incorrect in some cases, may prevent patients from seeking out other testing opportunities, taking the necessary precautions to prevent the transmission of HIV, and receiving the care and treatment that they need.

Additional Challenges of Rapid HIV Screenings

Poor Staff Training

Despite the probability of misdiagnoses, the use of rapid testing continues to become an increasingly popular screening method for HIV because of its ease and affordability. The number of people who are now able to receive testing has drastically increased. Problematically, the number of medical professionals available to administer the tests and interpret the results has not increased proportionally, leaving clinic staff with less training and experience to run testing centers in some areas.(14) Advocates for rapid testing argue that one of its primary advantages is that it requires little training on the part of the staff administering the tests, making widespread testing feasible in low-resource areas.(15) Underestimating the value of staff training is a critical flaw in rapid testing methodology, as this can adversely impact the quality of care and accuracy of results that patients receive. In the United States, training standards for administering rapid HIV tests are not uniform.  In most community-based organizations, training procedures provided to clinic staff fail to meet the standards set by the U.S. Center for Disease Control and Prevention (CDC).(16)  Further complicating the issue, rapid testing technology is evolving so quickly that training protocol must be updated, and training must be provided regularly in order to ensure that testing procedures are followed correctly.  Unfortunately, the evolving technology in combination with the already poor training standards are resulting in mediocre care and unreliable results for patients who seek rapid HIV testing. (17)   

The lack of well-trained professionals available to administer testing not only affects the efficacy of the results, but also the quality of counseling that patients receive.  Dr. Phil Berger, the chief of medical and community medicine at Saint Mary’s Hospital in Toronto and a proponent of the importance of quality counseling, explains: “Counseling is the standard of care that must be met in any HIV testing. My worry is that counseling won’t occur if testing is being done by a range of professionals who aren’t necessarily trained in counseling.“(18) The value of counselor training, like staff training, is often underestimated and overlooked. Clinic staff members conducting counseling often lack the skills necessary to provide adequate assistance with crisis intervention and are less effective in terms of helping an HIV-positive individual cope with the results.(19) As the use of rapid testing continues to expand, it is imperative that more of an emphasis be placed on counselor training. Quality counseling significantly increases the likelihood that a patient who is diagnosed with HIV will follow the preventative guidelines for reducing HIV transmission and will socially and emotionally cope better with his or her diagnosis.(20)

Ambiguous Test Results

Results from rapid HIV tests are sometimes subjective and difficult to interpret. Tests yielding faint lines, for example, may be interpreted as positive or negative depending on the staff member’s personal interpretation. Ambiguous results combined with poorly trained or inexperienced staff greatly increases the likelihood of inaccurate interpretations of results. Such subjectivity undoubtedly contributes to the high rate of false positive results produced by rapid testing.(21) In fact, testing instructions for many rapid HIV tests state that any amount of red in the patient box should be interpreted as a positive result.(22) This is problematic because the low-level reactivity responsible for weak or indeterminate results is present for individuals who are both HIV-positive and HIV-negative.(23) Thus, weak results should be interpreted as indeterminate rather than conclusive, and the results should be sent to a laboratory for further testing.(24) In circumstances where additional testing is required, the unreliable nature of rapid testing negates one if its primary benefits in that a laboratory and expensive equipment are then needed to interpret and deliver accurate results.

Allocation of Testing Resources

As rapid HIV screening technology opens the door for widespread testing, it is critical to ensure that individuals at the highest risk for contracting HIV are receiving testing.  Publicly-funded community screenings and health fairs need to ensure that they are testing people who are least likely to receive testing elsewhere and are most likely to be HIV-positive.(25) Unfortunately, it can be difficult to ensure that testing resources are going to populations that need it the most. Therefore, it is essential that public health officials carefully consider the most effective ways to advertise for health screenings. Radio, newspaper, or television commercials promoting free HIV screenings are more likely to attract individuals who can read or have access to a TV or radio.  Of those individuals who hear about the health fairs and screenings, only those with a private mode of transportation, access to public transportation, or people who live within walking distance may be able to attend. As the number of individuals screened for HIV each year continues to increase due to rapid testing, it is critical to ensure that testing resources are directed towards high-risk populations by offering testing in non-traditional venues such as emergency rooms, jails, and mobile clinics.(26)

Ethical Concerns

Although testing is considered to play an essential role in preventing the spread of HIV, knowledge about one’s HIV-positive status is not always favorable. Some countries, such as Botswana, have adopted routine testing as the primary method of detecting and identifying citizens who are HIV-positive.  Rather than waiting for patients to come in for voluntary counseling and testing, clinicians are required to administer routine testing of all patients. Compulsory testing strategies raise ethical concerns since patients are not given the option to choose whether or not they would like but tested. (27) Clinicians simply inform patients that they will be tested for HIV, and although the patient has the right to refuse testing, many patients remain unaware of this right, or feel uncomfortable denying testing that is clearly considered favorable by the clinic staff.  Patients are less likely to opt out of routine testing because they do not want to deviate from the apparent norm, which in this case is based on the policy that everyone should get tested.(28) The patient’s right to give informed consent is significantly compromised under these circumstances.

The World Health Organization’s Policy Statement regarding HIV testing strongly recommends that clinicians adhere to the three C’s of screening: confidentiality of results, counseling before and after testing, and consent to be tested. In addition to jeopardizing informed consent, routine and mandatory HIV screenings do not allow for pre-test counseling, a critical aspect of the HIV screening and diagnosis process. (29) The high prevalence of false positive results generated by rapid testing makes the need for pre-test counseling even more critical. It is unethical for patients to receive an HIV test without first being notified about the chances of receiving a false positive result.  When a false positive result does occur, it can have a drastic impact on the patient’s life. An ethically sound testing program “must make sure that people understand the meaning of the test, including the possibility of false positives and the window before the infection can be detected. People should know what their chances of being infected are.”(30) The elimination of pre-test counseling at health screenings and fairs due to rapid testing leaves patients with only one counseling session to ask questions, process their diagnosis, and receive advice. In contrast, traditional testing methods allowed patients to have several weeks to process the potential ramifications of their results and prepare questions for their next meeting with the counselor.(31) The widespread availability of rapid testing in conjunction with increasing pressure for routine HIV screenings is compromising the quality of care and the level of counseling that patients receive.

There is also growing concern that the lack of adequate pre-test counseling coupled with the movement towards compulsory testing may pressure patients into testing without allowing them to consider the personal impact of a true positive result.(32) In reality, the social and emotional consequences of an HIV-positive diagnosis are quite severe and can initially be more difficult to handle than the physical side effects. Those with HIV are more likely to be the victims of physical and verbal abuse and to be abandoned and ostracized by their friends, family, and community. (33) These risks are disproportionately higher for women, a fact that brings to light another ethical concern with routine testing. Since women are more likely to attend formal health care facilities, routine testing results in the screening of significantly more women than men. This emphasizes a substantial flaw in routine testing methodology.  “Advocates of routine testing have been accused of downplaying the social consequences of a HIV-positive status for women and girls in low-income countries to make the policy look more attractive,” a practice which unfairly subjects women to the discrimination of an HIV-positive status without considering the consequences.(34)

If a patient tests positively for HIV, as confirmed by traditional testing, it is important for the patient to receive treatment.  Botswana, for example, provides free, nation-wide antiretroviral treatment programs for its citizens. The availability treatment not only helps to mildly abate the harsh stigmatism surrounding the diagnoses but also makes routine testing policies more ethically appropriate. (35)  In many low-resource countries, however, such treatment options do not exist. In these types of circumstances, policymakers must seriously consider whether it is ethically sound to provide HIV testing. Within the Democratic Republic of Congo, for example, only 2% of patients who are diagnosed with HIV receive treatment and counseling. (36) In the case of mobile health clinics and community health fairs, follow up counseling and care are rarely feasible, as such clinics often move from location to location in an attempt to test hard-to-reach populations. Once given a diagnosis, a patient may not be able to access public services, if those services are even available, due to a lack of transportation, money, or knowledge and awareness.(37)  “In resource-poor settings, a lack of coordination and integration between routine HIV testing and treatment access threatens to sabotage the desired convergence between human rights aspirations and public health goals.”(38)

Improving Accuracy of Rapid HIV Testing in Resource-Limited Countries

Despite its shortcomings and disadvantages, rapid HIV testing has the potential to become a valuable and reliable tool. Research suggests that with improved staff training and the right sequence of tests, the accuracy of results generated from rapid HIV testing can be significantly improved.  In resource-limited countries, current rapid HIV testing methodology consists of administering each patient two different rapid tests. If both tests are negative, the patient is diagnosed as HIV-negative. If both tests are positive, the patient is diagnosed as HIV-positive. If the results are discordant, testing is repeated.(39) A recent study conducted in KwaZulu Natal found that rapid testing sensitivity could be greatly improved by using the right combination of rapid tests and by strictly monitoring quality control and staff training. Testing sensitivities increased from 68.7% to 93.5% after changing test brands and then improved even further to 95.1% after tightening quality control measures and retraining clinic staff.(40) Although these results still do not meet the World Health Organization’s standards for HIV testing sensitivity ratings, the study demonstrates rapid HIV testing’s potential for improvement.

In terms of selecting the most reliable and accurate testing combinations, researchers suggest that clinics should pair tests based on sensitivity and specificity ratings. For example, some tests have sensitivity ratings that are nearly 100%, but specificity ratings closer to 80%. Such a test should be administered in combination with a rapid test whose specificity is as close as possible to 100% in order to compensate for the low specificity of the first test.(41) Ideally, testing sensitivities, specificities, and positive predictive values for a single test should all meet World Health Organization standards.  However, until rapid screening technology improves, pairing rapid tests is considered the current best option in low-resource countries. Additionally, any weakly negative or weakly positive results should be re-tested to confirm a diagnosis.(42) In areas with access to laboratory equipment, confirmatory testing should be used to verify rapid testing results in order to reduce the probability of false positives.(43)

An additional method to minimize the chances of receiving false-positive results is to ensure that the two rapid tests used to create a clinic’s testing algorithm do not test for the same antibodies.(44) Many rapid diagnostic tests for HIV utilize the gp41 antigen as the target antigen for detecting HIV, meaning that if any gp41 in the blood sample being tested, the test will produce positive results. According to recent studies conducted in the Eastern Democratic Republic of Congo, “the finding of a single gp41 reaction in 50% of our false positive cases is of particular concern because gp41 is shared by multiple RDT [rapid diagnostic test] tests as a target antigen, and can therefore cause double false positive reactions.”(45) Thus, using combinations of rapid tests that screen for the same antibody is more likely to produce inaccurate results and should be avoided.

A Model of Care

Rapid HIV screenings conducted at community health fairs and in public clinics should be administered by experienced professionals or by well-trained clinic staff. Test manufacturers and clinic supervisors should conduct training workshops and seminars on a regular basis in order to ensure that staff members remain up to date on the most current testing technologies and procedures. (46) Additionally, all clinics should be staffed with professional counselors who are prepared to deliver results quickly and compassionately. Counselors must be well versed in the details of the test being used, which includes the ability to provide patients with the statistics concerning testing accuracy. In order to maintain the quality of counseling provided to patients, clinic supervisors should ensure that there are systems in place to provide emotional support for counselors when needed.(47) Counseling should not end at the time of diagnosis, but rather should mark the beginning of a long-term relationship between patients and clinic staff.  Relationships should be maintained by scheduling subsequent appointments at the clinic after results are provided or through home-visits by counselors, nurses, or physicians if the patient is unable to access reliable transportation.(48)

The primary goals of public clinics and health fairs should include prevention and treatment as well as testing and HIV identification. Even if a patient is given a negative diagnosis, he or she should still receive counseling and preventative care in order to reduce the likelihood of HIV transmission at a future time.(49) This includes explaining that even if one partner is infected and the other is not, there are ways to reduce transmission to the uninfected partner.(50)  It is suggested that clinics should advise all patients to use condoms, ensure that they are aware of how to use them properly, and provide condoms for free. Additionally, HIV-negative patients should be scheduled for a check-up and HIV screening every sixth months.(51) Patients diagnosed as HIV-positive should receive the same educational and preventative information as those who are HIV-negative, but should also receive treatment and additional counseling and emotional support through the clinic. (52)

Conclusion

Unfortunately, many clinics are understaffed and underfunded, making it difficult to provide and administer adequate testing and care for patients seeking rapid HIV screenings.(53) Even within the best clinics, the disadvantages of screening with rapid HIV tests are cause for concern. Although rapid testing has allowed for an unprecedented increase in the number of people who are able to receive testing through community health fairs and clinics worldwide, testing accuracy and reliability remain unacceptably poor. Moreover, the current benefits of rapid testing are polluted by screening errors and ethical concerns. Perhaps with stringent quality control, better testing technology, the right combination of tests, and well-trained staff administering and interpreting results, rapid testing will develop into a more reliable and ethically sound screening option for HIV.

Footnotes

(1) “Basic Information about HIV and AIDS.” Department of Health and Human Services Centers for Disease Control and Prevention. Accessed online on 16 November 2010.

(2) Heneke, M. "An analysis of HIV-related law in South Africa: progressive in text, unproductive in practice." Transnational Law & Contemporary Problems 18.3 (2009): 751. Accessed on 9 November 2010.

(3) Parisi, M., et, al. “Offer of rapid testing and alternative biological samples as practical tools to implement HIV screening programs.” New Microbiologica. 32 (2009) 391-396. Accessed on 2 November 2010.

(4) Constantine, N. and Zink, H. “HIV testing technologies after two decades of evolution.” Indian Journal of Medical Research. 121.4 (2005): 519 -538. Accessed on 28 November 2010.

(5) Sibbald, Barbara. "New rapid HIV test opens Pandora's box of ethical concerns." Canadian Medical Association Journal 162.11 (2000): 1600. Accessed on 7 November 2010.

(6) Gray, R., et al. “Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study.” BMJ. 335.7612 (2007): 335. Accessed on 2 November 2010.

(7) Ibid.

(8) Aghokeng, A., et al. “Inaccurate Diagnosis of HIV-1 Groupe M and O is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon.” PLOS One.  4.11 (2009). Accessed on 2 November 2010.

(9) Klarkowski, D., et. al. “The Evaluation of Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm.” PLUS One. 4.2 (2009). Accessed on 2 November 2010.

(10) Aghokeng, A., et. al. “Inaccurate Diagnosis of HIV-1 Groupe M and O is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon.” PLUS One. 4.11 (2009). Accessed on 2 November 2010.

(11) Ibid.

(12) Wolpaw, B., et. al.  "The failure of routine rapid HIV testing: a case study of improving low sensitivity in the field." BMC Health Services Research. 10 (2010): 73. Accessed on 7 November 2010.

(13) Aghokeng, A., et. al. “Inaccurate Diagnosis of HIV-1 Groupe M and O is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon.” PLUS One. 4.11 (2009). Accessed on 2 November 2010.

(14) Grusky, O., Roberts, K. and Swanson, A. "Failure to return for HIV test results: a pilot study of three community testing sites." Journal of the International Association of Physicians in AIDS Care. 6.1 (2007): 47+. Accessed online on 7 November 2010.

(15) Constantine, N. and Zink, H. “HIV testing technologies after two decades of evolution.” Indian Journal of Medical Research. 121.4 (2005): 519 -538. Accessed on 28 November 2010.

(16) Grusky, O., Roberts, K. and Swanson, A. "Failure to return for HIV test results: a pilot study of three community testing sites." Journal of the International Association of Physicians in AIDS Care. 6.1 (2007): 47+. Accessed online on 7 November 2010.

(17) Ibid.

(18) Sibbald, B. "New rapid HIV test opens Pandora's box of ethical concerns." Canadian Medical Association Journal 162.11 (2000): 1600. Accessed on 7 November 2010.

(19) Galvin, F., Brooks, R. and Leibowitz, A. “Rapid HIV Testing: Issues in Implementation.” AIDS Patient Care and STDs. 18.1 (2004) 15-18. Accessed Online 23 November 2010.

(20) Mwamburi, D., Dladla, N., Qwana, E. and Lurie, M. “Factors Associated with Wanting to Know HIV Results in South Africa.” AIDS Patient Care and STDs. 19.8 (2005): 518 – 525. Accessed on 28 November 2010.

(21) Klarkowski, D., et. al.“The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm” PLUS One. 4.2 (2009) Accessed on 2 November 2010

(22) Gray, R., et. al. “Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study.” BMJ (2007) Accessed on 2 November 2010.

(23) Parisi, M., et. al. “Offer of rapid testing and alternative biological samples as practical tools to implement HIV screening programs.” New Microbiologica. 32 (2009): 391-396. Accessed on 2 November 2010.

(24) Gray, R., et. al. “Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study.” BMJ (2007) Accessed on 2 November 2010

(25) Galvin, F., Brooks, R. and Leibowitz, A. “Rapid HIV Testing: Issues in Implementation.” AIDS Patient Care and STDs. 18.1 (2004) 15-18. Accessed Online 23 November 2010.

(26) Ibid.

(27) Rennie, S., and Frieda B. "Desperately seeking targets: the ethics of routine HIV testing in low-income countries." Bulletin of the World Health Organization. 84.1 (2006): 52+. Accessed on 9 November 2010.

(28) Johnson, E., and Goldstein, D. "Do defaults save lives?" Science 302.5649 (2003): 1338+. Accessed on 9 November 2010.

(29) Brockway, G. "Routine testing for HIV/AIDS in sub-Saharan Africa: a philosopher's perspective." Studies in Family Planning 38.4 (2007): 279+. 9 Accessed on 9 November 2010.

(30) Gersovitz, M. “HIV Testing: Principles and Practice.” The World Bank Research Observer. 25.2 (2010). Accessed on 30 November 2010. <

(31) Galvin, F., Brooks, R. and Leibowitz, A. “Rapid HIV Testing: Issues in Implementation.” AIDS Patient Care and STDs. 18.1 (2004) 15-18. Accessed Online 23 November 2010.

(32) Brockway, G. "Routine testing for HIV/AIDS in sub-Saharan Africa: a philosopher's perspective." Studies in Family Planning 38.4 (2007): 279. Accessed on 9 November 2010.

(33) Ibid.

(34) Rennie, S., and Frieda B. "Desperately seeking targets: the ethics of routine HIV testing in low-income countries." Bulletin of the World Health Organization. 84.1 (2006): 52+. Accessed on 9 November 2010.

(35) Ibid.

(36) Ibid.

(37) Galvin, F., Brooks, R. and Leibowitz, A. “Rapid HIV Testing: Issues in Implementation.” AIDS Patient Care and STDs. 18.1 (2004) 15-18. Accessed Online 23 November 2010.

(38) Rennie, S., and Frieda B. "Desperately seeking targets: the ethics of routine HIV testing in low-income countries." Bulletin of the World Health Organization. 84.1 (2006): 52+. Accessed on 9 November 2010.

(39) Klarkowski, D., et. al. “The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm” PLUS One. 4.2 (2009) Accessed on 2 November 2010.

(40) Wolpaw, B., et. al. "The failure of routine rapid HIV testing: a case study of improving low sensitivity in the field." BMC Health Services Research. 10 (2010): 73. Accessed on 7 November 2010.

(41) Aghokeng, A., et. al. “Inaccurate Diagnosis of HIV-1 Groupe M and O is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon.” PLOS One.  4.11 (2009). Accessed on 2 November 2010.

(42) Klarkowski, D., et. al. “The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm” PLUS One. 4.2 (2009) Accessed on 2 November 2010.

(43) Parisi, M., et. al. “Offer of rapid testing and alternative biological samples as practical tools to implement HIV screening programs.” New Microbiologica. 32 (2009): 391-396. Accessed on 2 November 2010.

(44) Klarkowski, D., et. al. “The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm” PLUS One. 4.2 (2009) Accessed on 2 November 2010.

(45) Ibid.

(46) Grusky, O., Roberts, K., and Swanson, A. "Failure to return for HIV test results: a pilot study of three community testing sites." Journal of the International Association of Physicians in AIDS Care. 6.1 (2007): 47+. Accessed online on 7 November 2010.

(47) Galvin, F., Brooks, R., and Leibowitz, A. “Rapid HIV Testing: Issues in Implementation.” AIDS Patient Care and STDs. 18.1 (2004) 15-18. Accessed Online 23 November 2010.

(48) “The Four Pillars of HIV Prevention and Care.” Partners in Health. 2.2 (2010). Accessed on 2 November 2010.

(49) Ibid.

(50) Gersovitz, M. “HIV Testing: Principles and Practice.” The World Bank Research Observer. 25.2 (2010). Accessed on 30 November 2010

(51) “The Four Pillars of HIV Prevention and Care.” Partners in Health. 2.2 (2010). Accessed on 2 November 2010.

(52) Ibid.

(53) Ibid.