Name: comprehensive &amp; cost effective laboratory monitoring of hiv/aids: an african role model
Uploaded: 2010-10-31T17:00:00
Duration: 23 min 56 s
Description: Watch this Scientific Journal Video about Comprehensive & Cost Effective Laboratory Monitoring of HIV/AIDS: an African Role Model at JoVE.com

Special thanks are due to the National Health Laboratory Service (NHLS) of the Republic of South Africa for the national organization of the HIV related flow diagnostic services (http:\\www.nhls.ac.za and http://www.plgcd4.net). The studies featured have been carried at the Department of Haematology and Molecular Medicine, Witwatersrand University (Johannesburg, South Africa; supported by Head of Department, Professor Wendy Stevens). The authors have received no grant support for this publication from commercial companies or funding agencies . The opinions expressed are those of the authors without necessarily reflecting the views of the Institutions of the University of the Witwatersrand or the South African NHLS.

<ol>
	<li>Mugyenyi, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Routine+versus+clinically+driven+laboratory+monitoring+of+HIV+antiretroviral+therapy+in+Africa+(DART):+a+randomized+non-inferiority+trial.">Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomized non-inferiority trial.</a> Lancet. 375, 123-131 (2009).</li><li>Donnell, D., Kiarie, J., Thomas, K., Baeten, J., Lingappa, J., Cohen, C., Celum, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ART+and+risk+of+heterosexual+HIV-1+transmission+in+HIV-1+serodiscordant+African+couples:+A+Multinational+Prospective+Study.">ART and risk of heterosexual HIV-1 transmission in HIV-1 serodiscordant African couples: A Multinational Prospective Study.</a> , (2010).</li><li>Montaner, J., Wood, E., Kerr, T., Yip, B., Lima, V., Shannon, K., Harrigan, R., Hogg, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Association+of+Expanded+HAART+Coverage+with+a+Decrease+in+New+HIV+Diagnoses,+Particularly+among+Injection+Drug+Users+in+British+Columbia,+Canada.">Association of Expanded HAART Coverage with a Decrease in New HIV Diagnoses, Particularly among Injection Drug Users in British Columbia, Canada.</a> , (2010).</li><li>Petti, C. 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H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+fragile+environments+of+inexpensive+CD4++T-cell+enumeration+in+the+least+developed+countries:+strategies+for+accessible+support.">The fragile environments of inexpensive CD4+ T-cell enumeration in the least developed countries: strategies for accessible support.</a> Cytometry B Clin Cytom. 74, S107-S116 (2008).</li><li>Glencross, D. K., Coetzee, L. M., Lawrie, D., Sanne, I., McIntyre, J. A., Janossy, G., Stevens, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+monitoring+of+CD38+activation+can+obviate+costly+viral+load+testing+in+60%+of+patients+on+ART.">Longitudinal monitoring of CD38 activation can obviate costly viral load testing in 60% of patients on ART.</a> , (2009).</li><li>Bergeron, M., Lustyik, G., Phaneuf, S., Ding, T., Nicholson, J. K., Janossy, G., Shapiro, H., Barnett, D., Mandy, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stability+of+currently+used+cytometers+facilitates+the+identification+of+pipetting+errors+and+their+volumetric+operation:+&#34;time&#34;+can+tell+all.">Stability of currently used cytometers facilitates the identification of pipetting errors and their volumetric operation: &#34;time&#34; can tell all.</a> Cytometry B Clin Cytom. 52, 37-39 (2003).</li><li>Coulter, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Flow Cytometer Alignment Verification Package insert of Flow-CheckTM Fluorospheres. Volume PN 4276179-LA. , (2008).</li><li>Coulter, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Flow-SetTM Fluorospheres (Flow Cytometer Standardization Fluorospheres). Package insert of Flow-SetTM Fluorospheres. Volume PN 6607007. , (2007).</li><li>Coulter, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Immuno-TrolTM Cells. Package insert of Immuno-TrolTM Cells. Volume PN 6607077. , (2007).</li><li>. Beckman Coulter Hematology IQAP program Available from: <a target="_blank" href="https://www.beckmancoulter.com/wsrportal/wsr/support/quality-assurance-programs/interlaboratory-quality-assurance-program-iqap/index.htm">https://www.beckmancoulter.com/wsrportal/wsr/support/quality-assurance-programs/interlaboratory-quality-assurance-program-iqap/index.htm</a> (2009)</li><li>Glencross, D. K., Aggett, H. M., Stevens, W. S., Mandy, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=African+regional+external+quality+assessment+for+CD4+T-cell+enumeration:+development,+outcomes,+and+performance+of+laboratories.">African regional external quality assessment for CD4 T-cell enumeration: development, outcomes, and performance of laboratories.</a> Cytometry B Clin Cytom. 74, S69-S79 (2008).</li><li>Tilling, R., Kinloch, S., Goh, L. 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K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interpretation+of+CD45+patterns+in+the+PanLeucoGating+CD4+test+can+be+used+for+diagnosis+of+white+cell+abnormalities.">Interpretation of CD45 patterns in the PanLeucoGating CD4 test can be used for diagnosis of white cell abnormalities.</a> Poster presentation. , (2007).</li><li>Lawrie, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+wide-spread+clinical+uses+of+PanLeucoGating+technology+in+the+HIV+diagnosis+oriented+immunohaematology+laboratory.">The wide-spread clinical uses of PanLeucoGating technology in the HIV diagnosis oriented immunohaematology laboratory.</a> PhD Thesis, in preparation. , (2010).</li><li>Badri, M., Lawn, S. D., Wood, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Utility+of+CD4+cell+counts+for+early+prediction+of+virological+failure+during+antiretroviral+therapy+in+a+resource-limited+setting.">Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting.</a> BMC Infect Dis. 8, 89 (2008).</li><li>Peter, T., Badrichani, A., Wu, E., Freeman, R., Ncube, B., Ariki, F., Daily, J., Shimada, Y., Murtagh, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Challenges+in+implementing+CD4+testing+in+resource-limited+settings.">Challenges in implementing CD4 testing in resource-limited settings.</a> Cytometry B Clin Cytom. 74, S123-S130 (2008).</li><li>Denny, T. N., Gelman, R., Bergeron, M., Landay, A., Lam, L., Louzao, R., Mandy, F. F., Schmitz, J., Spira, T., Wilkening, C., Glencross, D. 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The international patent rights for CD4 method described here are held by the South African NHLS and currently under license to BCI, Miami, Fl, USA.

In recent years the charity-driven and grant-allocated programs have helped the establishment of some excellent clinical practices in resource limited areas of the globe with high HIV burden. The ART programs have been successful in reducing the mortality and are now being initiated at higher CD4 counts 2,3. There are already indications that these new measures will decrease the spread of HIV infection 4,5, despite the lack of a HIV-specific vaccine. In our video we document that when monitoring patients on ART, these techniques can be better focused and become more cost-effective than that observed in the routine practice performed in western laboratories (List 1).
Such an African-led approach may well be essential to support the upgrading of laboratory services at a time when HIV infection, treated with ART, is becoming a chronic disease. Such a monitoring of ART requires precise CD4 counting and viral-load related technology, a more demanding task than to simply perform a CD4-count for placing patients into arbitrary groups in order to assist a decision about starting ART 16. With the help of these diagnostics, i.e. using the CD8/CD38 test, it is possible to reduce the VL-related monitoring costs in &gt;60% of the patients on ART 16,19. It is also important to emphasize that it is the CD8/CD38 test 16,17, and not the CD4 count 37, which is likely to pick up early signs of VL rebounds and/or the lack of patient compliance in taking the medication.
An essential element of a coordinated cost-effective central service is the availability of a large-scale national or regional network supported by experts and academic advisers who are familiar with the technical and medical aspects of the operation. This is demonstrated by the activities of the South African NHLS network and the CD4-PLG.net training schemes 33, 36 which provide encouragement, education and quality assessment for the smaller centres and these may also include 'point-of-care' services.
Importantly, the operations of central and point-of-care laboratories are complementary. While the former has the double role of providing a cost-effective large-scale service operation as well as basic/advanced training for the peripheral laboratories 33,38, the latter contributes to check the spread of ART by recruiting HIV+ patients who are eligible for ART from a larger base, including rural clinics. Here some caution is necessary because point-of-care diagnostics can be much more expensive and do not automatically guarantee accuracy 38. It is therefore sensible to retain the two-tier system and to facilitate coordination between the two tiers without allowing either arm to dwindle.
In conclusion, in the field of the diagnostic monitoring of the clinical management of infectious diseases a necessary cost-saving can be achieved by apt services that use less expensive and better coordinated modern technology with a significantly improved quality 13,39. Well-organized national (and regional) diagnostic service provisions should be better supported 6-8 by avoiding a scenario when virtually all grant support is wasted on expensive and/or untried methods as soon as these are imported from rich countries without a careful pre-emptive constructive scrutiny. Similarly, a more flexible design of clinical therapeutic trials with the full involvement of local doctors and healthcare personnel should lead to the reduction of unnecessarily frequent and/or over-ambitious laboratory testing 3. This policy would give more chance to a fuller utilization of the available accurate diagnostic results in a coordinated clinical/laboratory assessment of patients on ART. These smart diagnostics could also be pioneered for the resource-poor countries 8 in the areas of tuberculosis and leukaemias using an existing familiar flow cytometric platform 40.

comprehensive &amp; cost effective laboratory monitoring of hiv/aids: an african role model

We present the video about assisting anti-retroviral therapy (ART) by an apt laboratory service - representing a South-African role model for economical large scale diagnostic testing. In the low-income countries inexpensive ART has transformed the prospects for the survival of HIV seropositive patients but there are doubts whether there is a need for the laboratory monitoring of ART and at what costs - in situations when the overall quality of pathology services can still be very low. The appropriate answer is to establish economically sound services with better coordination and stricter internal quality assessment than seen in western countries. This video, photographed at location in the National Health Laboratory Services (NHLS-SA) at the Witwatersrand University, Johannesburg, South Africa, provides such a coordinated scheme expanding the original 2-color CD4-CD45 PanLeucoGating strategy (PLG). Thus the six modules of the video presentation reveal the simplicity of a 4-color flow cytometric assay to combine haematological, immunological and virology-related tests in a single tube. These video modules are: (i) the set-up of instruments; (ii) sample preparations; (iii) testing absolute counts and monitoring quality for each sample by bead-count-rate; (iv) the heamatological CD45 test for white cell counts and differentials; (v) the CD4 counts, and (vi) the activation of CD8+ T cells measured by CD38 display, a viral load related parameter. The potential cost-savings are remarkable. This arrangement is a prime example for the feasibility of performing &gt; 800-1000 tests per day with a stricter quality control than that applied in western laboratories, and also with a transfer of technology to other laboratories within a NHLS-SA network. Expert advisors, laboratory managers and policy makers who carry the duty of making decisions about introducing modern medical technology are frequently not in a position to see the latest technical details as carried out in the large regional laboratories with huge burdens of workload. Hence this video shows details of these new developments.

Watch this Scientific Journal Video about Comprehensive & Cost Effective Laboratory Monitoring of HIV/AIDS: an African Role Model at JoVE.com

Comprehensive & Cost Effective Laboratory Monitoring of HIV/AIDS: an African Role Model

Anti-retroviral therapy to treat HIV/AIDS is monitored in South Africa on a large scale. Flow cytometry is combined for haematology (CD45), immunology (CD4) and viral-load linked CD38 assay. Recorded at NHLS-SA laboratories, Johannesburg, these modern methods are cost-efficient with heightened local internal quality control, serving as role-models for resource-limited diagnostics.

Comprehensive &amp; Cost Effective Laboratory Monitoring of HIV/AIDS: an African Role Model

We present the video about assisting anti-retroviral therapy (ART) by an apt laboratory service - representing a South-African role model for economical ...

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Safety Precautions and Operating Procedures in an ABSL-4 Laboratory: 2. General Practices

Sikkerhetstiltak og driftsprosedyrer i en (A) BSL-4 Laboratorium: 2. Generelle Practices

Work in a biosafety level 4 (BSL-4) containment laboratory requires time and great attention to detail. The same work that is done in a BSL-2 laboratory ...

Bioluminescence Imaging to Detect Late Stage Infection of African Trypanosomiasis

Bioluminesens Imaging å oppdage sent stadium smitte av sovesyke

Human African trypanosomiasis (HAT) is a multi-stage disease that manifests in two stages; an early blood stage and a late stage when the parasite invades ...

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291

Cefoperazone behandlet musemodell for klinisk relevante<em&gt; Clostridium difficile</em&gt; Strain R20291

Clostridium difficile is an anaerobic, gram-positive, spore-forming enteric pathogen that is associated with increasing morbidity and mortality and ...