Technological challenges in diagnosis and management of HIV infection

[Guest guest]

Technological challenges in diagnosis and management of HIV infection

in resource limited settings.

Purnima Madhivanan and Karl Krupp

doi:10.1136/bmj.39275.457188.AE 2007;335;165-166 BMJ pp 188, 190

Relatively quick and cheap tests can work but must be properly

monitored

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

( & #8722;48.9 to 27.0 cells/ìl for absolute counts in the CD4 range <400

cells/ìl, and & #8722;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 $100 000 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 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 various 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 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

1. MacLennan CA, Liu MKP, White SA, Oosterhout JJGv, Simukonda F,

Bwanali J, et al. Diagnostic accuracy and clinical utility of a

simplified low-cost flow-cytometric CD4 counting method in Malawi.

BMJ 2007 doi: 10.1136/bmj.39268.719780.BE

2. Gray RH, Makumbi F, Serwadda D, Lutalo T, Nalugoda F, Opendi P, et

al. Limitations of rapid HIV-1 tests during screening for trials in

Uganda: diagnostic test accuracy study. BMJ 2007 doi:

10.1136/bmj.39210.582801.BE

3. World Health Organization. Scaling up antiretroviral therapy in

resource-limited settings. Geneva: WHO, 2002.

www.who.int/3by5/publications/documents/arv_guidelines/en/

4. Thorstensson R, Andersson S, Lindback S, Dias F, Mhalu F, Gaines

H, et al. Evaluation of 14 commercial HIV-1/HIV-2 antibody assays

using serum panels of different geographical origin and clinical

stage including a unique seroconversion panel. J Virol Methods

1998;70:139-51.

5. Kassler WJ, Alwano-Edyegu MG, Marum E, Biryahwaho B, Kataaha P,

Dillon B. Rapid HIV testing with same-day results: a field trial in

Uganda. Int J STD AIDS 1998;9:134-8.

6. Nkengasong JN, Maurice C, Koblavi S, Kalou M, Yavo D, Maran M, et

al. Evaluation of HIV serial and parallel serologic testing

algorithms in Abidjan, Cote d'Ivoire. AIDS 1999;13:109-17.

7. Andersson S, da Silva Z, Norrgren H, Dias F, Biberfeld G. Field

evaluation of alternative testing strategies for diagnosis and

differentiation of HIV-1 and HIV-2 infections in an HIV-1 and HIV-2-

prevalent area. AIDS 1997;11:1815-22.

Purnima Madhivanan . PhD candidate, Division of Epidemiology, School

of Public Health, University of California, Berkeley, CA94720-7350,

USA

Karl Krupp programme director, Public Health Research Institute,

CSIHoldsworth Memorial Hospital, POBox 38, Mysore, Karnataka, India

e-mail: mpurnima@...