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Relatively quick and cheap tests can work but must be evaluated and monitored properly
With the HIV epidemic in its third decade, appropriate use of technology in resource limited settings has taken on added importance as priorities shift from detection and prevention to care and support for people living with HIV. At the same time, there is a continuing need for evaluation of and improvement in the critical diagnostic tools, such as rapid tests for HIV, which have become indispensable in settings with a high prevalence of infection.
In this week's BMJ two studies look at such evaluations. MacLennan and colleagues1 assess the diagnostic accuracy and clinical utility of a simplified flow cytometry method for measuring CD4 counts that promises a more affordable alternative for routine clinical use in resource limited settings. Gray and colleagues2 highlight problems encountered with the use of rapid tests for HIV screening in rural Rakai, Uganda.
As the world moves towards universal access to antiretroviral treatment, healthcare providers are confronted with many complexities in providing uninterrupted lifelong care. Clinical staging of HIV disease does not fully predict immunological status, and hence CD4 cell counts remain the most effective indicator for starting therapy and assessing immunological response to drug regimens. The World Health Organization has noted that “one of the most crucial needs in the developing world is universal access to affordable and locally usable CD4 testing technology.”3 The current shortage of laboratories that can perform counts in resource constrained settings jeopardises the success of campaigns to scale up antiretroviral treatment and distribute lifesaving drugs to millions of people living with HIV.
Current flow cytometry methods for CD4 counting, with reagents that cost from $3 (£1.50; €2.20) to $6 per test are expensive and possibly too complex for many resource constrained settings. MacLennan and colleagues compared BlantyreCount, a simplified counting method, with TruCount for both accuracy and clinical utility at a clinic for antiretroviral therapy in southern Malawi.1 BlantyreCount comprises “primary CD4 gating” using one antibody against CD4 and side scattered light to discriminate between lymphocytes and monocytes. This single platform method reduces the costs of reagents by more than 91% and makes laboratory procedures much simpler than those for existing flow cytometry methods. The authors show that the limits of agreement for BlantyreCount and TruCount are excellent (−48.9 to 27.0 cells/µl for absolute counts in the CD4 range <400 cells/µl, and −2.42% to 2.37% for %CD4/lymphocytes) but note that even this simplified method still requires a level of technical expertise not always present in resource poor settings. More importantly, the paper correctly points out that non-reagent costs, especially capital expenses and maintenance, which often come to more than $100000 for a flow cytometer instrument, may still limit applicability in many settings.
Gray and colleagues examine the issue of false positive tests during screening for a randomised trial of male circumcision for HIV prevention in Rakai, Uganda.2 The trial used a rapid HIV test algorithm to screen potential participants. Tests yielded “weak positive” bands that resulted in low specificity and low positive predictive values when confirmed using an enzyme immunosorbent assay and western blot. When weak positive bands were excluded, the number of false positives fell. This is an important finding because previous research had shown that algorithms combining two or more rapid tests resulted in very high levels of sensitivity and specificity.4 5 6 7
Although more research is needed to establish whether these results can be generalised to other populations and specific HIV subtypes, the study raises an important question that needs further exploration. Clearly, there is a compelling need to re-examine the performance of rapid tests in a variety of settings using a gold standard such as enzyme immunosorbent assay and western blot to verify results. Reducing the risk of false positives is important in both research and HIV testing programmes because of the stigma associated with having a positive HIV test.
What are the larger implications of these findings? Firstly, it is important that we continuously improve on existing technologies to make them more affordable, accurate, and widely available. Although the cost of flow cytometry is initially high, strategically located facilities such as regional centres for antiretroviral treatment can provide the high volume of patients needed to offset the capital investment, as long as reagents are affordable. Secondly, there is no dearth of talent in resource constrained settings; only a lack of political will to make the necessary investments in training and quality control. Finally, as HIV is such a serious and stigmatised condition, it is essential that we exercise vigilance to ensure that technologies are performing optimally. As Gray and colleagues suggest, it is prudent to routinely retest a sample of specimens using a gold standard method to maintain quality control.
Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.