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Moving Forward in Diagnosis of InfectiousDiseases in Resource Limited Countries:
a Focus on HIV
“Les Pensières”Fondation Mérieux Conference Centre
Veyrier-du-Lac - France
September 16-17, 2010Steering Committee:
•IsabelleANDRIEUXMEYER
•Jean-FrançoisDELFRAISSY
•Pierre-MarieGIRARD
•CatherineHANKINS
•ChristopheLONGUET
•JeanElieMALKIN
•SouleymaneMBOUP
•JohnNKENGASONG
•DominiquePEYRAMOND
•ValentinaPICOT
•GillesRAGIN
•ChristineROUZIOUX
•WendySTEVENS
•GabyVERCAUTEREN
•GuyVERNET
•MarcoVITORIA
WelcomeLetter
September 16, 2010
Dear Participant,
It is our pleasure to welcome you to the symposium entitled:
“Moving forward in diagnosisofinfectiousdiseasesinresourcelimitedcountries:
a focus on HIV”
in Fondation Mérieux’s Conference Centre “Les Pensières.” We hope you will enjoy this meeting, which brings together some of the world’s foremost experts in HIV.
The format of the meeting’s programme is intended to generate discussion and interaction among participants and to foster the dissemination of new information on this topic. The conference will provide an opportunity for specialists to exchange knowledge and experiences through collaboration with researchers from around the world.
Over the next two days, the team at Les Pensières will be on hand to help you with any questions you may have and to make your stay and conference as comfortable and valuable as possible.
Benoît Miribel Director General Fondation Mérieux
For more information: www.fondation-merieux.org
Backgroundandrationale In recognition of the critical constraints on the diagnosis of many infectious diseases affecting the developing world, Fondation Mérieux organizes an annual forum to increase awareness of the importance of strengthened diagnostics capacity in resource constrained settings. This forum provides a platform to international stakeholders and partnerships with the ultimate aim to improve care and treatment of affected individuals and to mitigate the impact of infectious diseases on the populations.
The objectives of the meeting are to:
· Increase awareness on the importance of adequate diagnosis of infectious diseases in resource limited countries; ·Highlightthespecificneedsinresource-constrainedsettings; · Learn about the diagnostic tools available and in research & development; · Exchange lessons learned from ongoing initiatives; · Agree on priorities to move forward and on the respective roles of partners. After two successful “Moving Forward” on tuberculosis and malaria, organized respectively with the STOP TB Partnership, the Global Laboratory initiative and the World Health Organization on tuberculosis in 2008; and with the Roll Back Malaria Partnership in 2009, Fondation Mérieux is pleased to co-organize the “Moving Forward 2010” with UNAIDS.
Thethirdannualforumfocusesonthediagnosisofthehumanimmunodeficiencyvirus(HIV)whichisresponsibleofa global epidemic with a devastating impact in developing countries. HIV has killed more than 25 million people since it wasfirstrecognized.Itisestimatedthatmorethan117millionpeoplewilldiefromthediseaseby2030;mostof them are in Africa. Universal access to prevention, diagnosis, treatment and care of HIV requires a wide range of actions. Among them the strengthening of laboratory services in underserved countries is important to meet the diagnostic challenges of HIV, and associated coinfections as tuberculosis. The development of new point of care tools and validation of new strategies are also necessary to improve access to the information about one’s own status and to ensure adequate follow up of antiretroviral treatment. The 2009 WHO recommendations outline an expanded role for laboratory monitoring to improve the quality of HIV treatment and care. They recommend greater access to CD4 testing and the use of viral load monitoring when necessary. However, access to ART must not be denied if these monitoring tests are not available.
2010 meeting objectives
The forum will bring together about one hundred international laboratory and clinician experts on HIV, decision makers and opinion leaders from high-burden countries, nongovernmental and patient-based organizations, representatives from the industry, researchers, representatives from the United Nations and other global institutions, international technical partners and leading funding agencies.
Alltheseactors,deeplyinvolvedintheHIVfield,willfocus,duringatwo-daysmeeting,onthechallengesofHIV diagnosis in resource limited countries and discuss how to move forward about them.
ScientificProgramme
Thursday 16 September 2010
08.00 - 08.10 Registration
08.10 - 08.25 WelcomeAddresses Alain MERIEUXPaul DE LAY
Keynote lectures
08.25-08.35 GlobalfightagainstHIV/AIDS:theFrenchstrategy Patrice DEBRE
08.35-08.50
Importance of HIV diagnosis in achievinguniversalaccesstoprevention, care and treatment in resourcelimitedcountries
Alexandra CALMY
08.50 - 09.10 2010WHOrecommendationsonHIV treatment and monitoring Marco VITORIA
Session 1 Challengesandneeds Chair: Jean Elie Malkin Co-Chair: Pierre-Marie Girard
09.10-09.30 Roleofcommunitybasedassociations on HIV testing Hakima HIMMICH
09.30-09.50
Constraintswiththeavailableimmuno-sero-virologicaldiagnostic tests in resource limitedcountries
François SIMON
09.50 - 10.10Choiceoftestsaccordingtothesetting/qualitycontrolandtestsvalidation
Avelin AGHOKONG
10.10-10.30 Discussion
10.30-10.50 Coffee break
10.50 - 11.10 DiagnosisissuesinPMTCT:experience in Cambodia Eric NERRIENET
11.10-11.30 Earlydiagnosisoffailuretotreat-mentinresourcelimitedcountries Charles KOUANFACK
11.30-12.00 Lostoffollowupandresistanceemergence Serge EHOLIE
12.00 - 12.15 Discussion
12.15-13.40 Lunch
ScientificProgramme
13.40-14.00 R&Dinimmunologicaltests Luc KESTENS
14.00 - 14.20 R&Dinvirologicaltests Christine ROUZIOUX
14.20-14.30 Discussion
Session 2 Researchanddevelopment Chair: Jean-François Delfraissy Co-Chair: Sophie Matheron
Session3 Strategies Chair: Catherine Hankins
14.30-14.50 Earlydiagnosisininfants Coumba TOURE
14.50 - 15.10 HIVincidenceassaysforpopulationsurveillance Andrea Y. KIM
15.10-15.30 IntegratingTB/HIVdiagnosticplat-formsinhighendemiccountries Giorgio ROSCIGNO
15.30-15.50
QuantificationofHIVviralloadtoassesstheneedtoswitchtosecondlineantiretroviraldrug.ExperiencefromthepublicsectorinMyanmar
Philippe CLEVENBERGH
15.50 - 16.10 Discussion
16.10 - 16.40 Coffee break
Panel HIV treatment monitoring strategies TheWHOpublichealthapproach:challengesanddifficulties Facilitator: Gilles Raguin
16.40 - 18.00WHO2009RecommendationDARTSTRATA
Robert COLEBUNDERSChristian LAURENTWendy STEVENS
ScientificProgramme
09.00 - 09.20 Pointofcareandinnovativetechnologies Wendy STEVENS
09.20 - 09.40 Capacitybuildingindiagnosticservices Souleymane MBOUP
09.40 - 10.00StrengtheningmonitoringofpatientswithAIDS:establishmentofHIV-1viralloadinLaoPDR
Phimpha PABORIBOUNE
10.00 - 10.20
Strengtheninglaboratorysystemsindevelopingcountries:implementingpracticalandaffordablequalitymanagementsystems
John NKENGASONG
10.20 - 10.40 Coffee break
10.40 - 11.00 ProcurementintheperspectiveoftheClintonFoundation Trevor PETER
11.00 - 11.40Fieldexperiences:-DREAMProgramme-AccordiaFoundation
Giovanni GUIDOTTIYuka MANABE
11.40 - 12.00 Discussion
12.00-13.30 Lunch
Friday17September2010
18.00 - 18.15 Panel conclusions
19.30 Welcome dinner
Session 4 Healthcaresystemstrengthening Chair: Deborah Birx Co-Chair: Gilles Brücker
ScientificProgramme
Group sessions 1)WhatarethethreeprioritestomoveforwardinthediagnosisofHIV indevelopingcountries? 2)Whoarethekeyactorsinthisprocessandwhatshouldbetheirrole?
13.30-15.00
I.Researchanddevelopment
II.Strategies
III.Healthcaresystemstrengthening
Facilitator: Steven BuchsbaumRapporteur: Martine Peeters
Facilitator: Giorgio RoscignoRapporteur: Julian Gold
Facilitator: Jean-François EtardRapporteur: Praphan Pranupak
15.00-15.30 Coffee break
15.30-15.50 GroupI
15.50 - 16.10 GroupII
16.10-16.30 GroupIII
16.30-16.45 Concluding remarks and closing
Plenary session Groupsplenaryrestitution Chair: Pierre-Marie Girard Co-Chair: Isabelle Andrieux Meyer
Keynotelectures
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Importance of HIV diagnosis in achieving universalaccess to prevention, care and treatment in resource limitedcountries
Alexandra CALMYGeneva University Hospital - Switzerland
- HIV epidemic is still uncontrolled, with daily new infections occurring more frequently than individuals initiating antiretroviral (ARV) therapy. There is a continuum between HIV screening,diagnosis of an HIV disease and initiation of antiretroviral therapy. Obstacles to an effective HIV epidemic control and universal access to care and treatment are multiple and include factors such as: stigma and discrimination preventing access to HIV screening, marginalized populations, health care provider-related causes etc. As an example, less than 20% of women in sub-Saharan Africa have an HIV tests during their pregnancy. Most HIV infections worldwide are discovered at the time of severe immune suppression. In Switzerland,halfofnewinfectionsarediagnosedbelow350CD4cell count. - Regular HIV screening at a population level as well as an effective linkage with HIV care and early ARV therapy ensure the best chances for epidemic control. - However, if all known HIV infected individuals had access to a well conducted ARV therapy according to established guidelines, a decrease in HIV transmission is expected (a 30% decreasetransmission could occur according to the mathematical model used).- This effect of antiretroviral therapy on HIV transmissibility recently prompted a change in US guidelines; ARV therapy is proposed for sero-discordant couples even if the HIV-infected individualwouldnotneeditforindividualbenefit.- Health care system, as well as ART program efficiencyneeds to be strengthened: retention in care will be a challenge in the coming years, as the number of treated patients is expected to rise dramatically. Also, we need to ensure that access to care will be equitable across countries, but also across regions: there are important disparities in treatment failure diagnosis as well as access to second line therapy between rural and urban regions.- Known prevention measures such as condoms distribution, male circumcision, screening of blood supply, needle exchange programs, education/behavioral changes and hopefully microbicides should implemented without delay – but given the effect of ART on reducing viremia, the use of ARV as a means for preventing transmission is central and should be combined with the other preventive measures. - Ultimately, a safe and effective vaccine would be a very effective measure – but not foreseen in a near future.
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2010 WHO recommendations on HIV treatment andmonitoring
Marco VITORIAWHO - Switzerland
WHO has recently updated the global recommendations on antiretroviral therapy, promoting earlier treatment initiation, use of less toxic drug regimens and expansion the role of laboratory monitoring, in order to increase the survival and improve the quality of HIV treatment and care. Recent evidence also suggests that an earlier start to treatment canhavesecondarypreventivebenefits, reducingHIVandTB transmission at population level. The objective of this presentation is to describe the rationale used on development of these new recommendations on ART, discussing the benefitsandchallengesontheirimplementation,particularlyin the context of resource limited settings.
Session 1
Challengesandneeds
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HIVTesting:theurgentneedtoinvolvecommunity-basedorganizations
Hakima HIMMICHCHU Ibn Rochd Casablanca - Morocco
WhereasAntiretroviral Therapy (ART) lowers the viral load andthereby decreases the risk of HIV transmission, whereas access to treatment has became a reality in limited-resources countries, only 12% of seropositive patients know their serological status. On the other hand, in several countries with concentrated epidemic, some key populations are particularly most affected by HIV infection. Hence, to scale-up HIV Testing and Counseling (HTC) uptake,it is necessary to combine multiple approaches, including the community approach. We report 2 communities experiences, one from the North, the second the South.The Moroccan Community-Based Organization, ALCS, has put in place, in the early 90’s, a very wide offer of HTC integrated into comprehensive outreach prevention programs targeting Men HavingSexwithMen(MSM)andSexworkers(SW)andprovidingafree,anonymousandconfidentialrapidHIVtesting(HIVrapidtestswere introduced in2004).Theservice isprovidedbyphysicians,volunteers, in stand-alone VCT units, in conviviality meeting points, but also in the cruising areas with the help of mobile HTC unit. FromJanuarytoJune2010,1017MSMwheretestedwith2.85%ofpositivetests,3099SWwheretestedwith2.13ofpositivetests.In France, the organization AIDES conducted recently a research project,fundedbyANRS(‘ANRSCOM’TEST’Study),offeringMSMpeer-based and rapid HTC. The rationale for the project was that the diagnosis of new infections in MSM is not improving and that there isaspecificneedtofrequentlyrepeattestinginthispopulation.Theservice was provided in community locations, during convenient hours. The preliminary results concerned 320 MSM and clearlyshowthepreferenceofofMSMforpeer-basedHTC(93%),with2to5%ofpositivetests,allconfirmedbyconfirmatorytests.Theexperience and satisfaction of clients were rated better than in the conventional model of HTC. These 2 experiences, meeting the needs of the targeted populations, share the absence of judgmental counseling, the use of HIV rapid testing technology, the provision of HTC in outreach locations, that infected people are more likely to visit, and the support of repetition of testing for the clients with frequent exposure to HIV infection.
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Constraintswiththeavailableimmuno-sero-virologicaldiagnostictestsinressourcelimitedcountries
François SIMONCHU Saint-Louis - France
Twentyfiveyearsaftertheintroductionofthefirstscreeningtestsand15yearsafterthefirstviralloadassays,diagnosisandmonitoringof HIV infections in developing countries remain problematic particularlyinprimaryhealthpointofcare(POC)inAfrica.1/HIVdiagnosisandconfirmatorystrategiesarestillfarfrombeingestablished all across the African territory. WHO recommendations toinvolvedifferentHIVrapidtests(RTD)inanalgorithmbasedonprevalenceareinsufficientintermsofsensitivityandspecificity.Furthermore, RTD performed onto capillary blood are less sensitive than thoseontoserum.Driedbloodspot (DBS)areprobably theonly alternative to improve the conditions of HIV screening in POC andtodevelopnewstrategiesforconfirmationincludingmolecular- based tools. A positive TDR in POC requires blood sampling onto DBS and shipment to a central laboratory where DBS will be tested byHIV-1PCRorNasbaandapositivemolecularassaywillconfirmthe infection. Samples found negative by PCR or Nasba should be explored on specificV3 loop peptides of HIV-2 andHIV-1N-O-Pvariants. 2/RNAquantification has limited value inmonitoring therapeuticin POC and can be easily replaced by clinical and haematological survey(CD4orlymphocytecounts).3/Conversely, improvingdrug resistancedetection ismandatory.Simpleandrobustqualitativetestsabletodetect3-4logofRNA/mL are urgently needed. Besides a surveillance by DBS, many promising devices are currently being evaluated in POC, but trials, results and implantation are still pending. 4/ Alternative techniques, such an ultra-sensitive detection of p24 antigen with immune-complexes dissociation remain poorly reproducible due to the diversity of p24 epitopes and must be improved. The first commercialized rapid tests offering a p24antigen detection lacks sensitivity and must be improved before a possible use for monitoring patients and children.
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ChoiceofHIVdiagnostictestsaccordingtothesetting:testsvalidationandqualitycontrol
Avelin F. AGHOKENGVirology Laboratory IMPM/IRD - Cameroon.UMR145, Institut de Recherche pour le Développement, University of Montpellier 1 - France
Increased access to HIV testing is essential in working towards uni-versal access to HIV prevention and treatment in resource-limited countries, especially in Africa where the majority of people infected with HIV live. Several million of HIV diagnostic tests are used every year in developing countries to detect HIV negative and HIV infec-ted patients and because of the tremendous expansion of rapid/simple assays, referral to a treatment center or treatment initiation can be done rapidly even in remote access areas with limited in-frastructures.Improving the access to HIV testing is essential, but the quality of HIV diagnosis in these settings should be assessed also. Recent studies conducted in few African countries showed that several is-sues are still pending on the quality of HIV testing and a relative im-portant proportion of results that are given to tested persons are not accurate, since these studies highlighted high proportion of false negative and false positive individuals. Some assays are not able to correctly detect infections with even the major HIV-1 group found worldwide which is group M, and their performance on divergent HIV strains as HIV-1 group O mainly found in West-Central Africa are very limited. The second key issue is the procedure of selection of tests that are intended for use in the countries. Good practices recommend that HIV assays projected for use in a country should befirstevaluatedonaserumpanelfrompatientsinfectedwithlo-cal and contemporary HIV strains to measure their performance, but also for their operational characteristics as storage conditions, equipment required, ease of use, etc. Unfortunately, this scenario is rarely applied due to inappropriate policies, practical constraints, limited resources and absence of laboratory experts in policyma-king and program planning. In practice, test kits are selected and orderedbygovernmentofficialswithnoor lowexperience inHIVdiagnosis and selection is often only based on the lower price and notalsoontestsefficacy.Also,becauseofineffectivesupplychainmanagement, stock-outs are frequent and as a consequence, when existing, HIV testing algorithms are not applied and testing strategiesarebasedonassaysthatareavailable.Andfinally,thethird important problem is the lack of national quality control policies including regular reassessment of tests used in the country and retraining of the health care personnel.
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Suite
Efforts are then needed to improve the quality of HIV diagnosis in resource-poor settings, as the demand for testings is increasing. There is a need to implement guidelines and provide resources for the validation of national testing strategies on a regular basis over time, and implementation of quality control programs in countries are essential to meet the goal of good HIV diagnosis in developing countries.
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DiagnosisIssuesinPMTCT:ExperienceinCambodia
Eric NERRIENETInstitut Pasteur - Cambodia
Background: Even remarkable progress has been made in scaling up prevention of mother to child transmission (PMTCT), theeffectiveness of PMTCT interventions is rarely documented in low-income countries. In this study, we estimate HIV vertical transmission rates and HAART outcomes among children diagnosed HIV-infected before the age of 18 months in Cambodia.
Methods:ByMay2010,1,617driedbloodspot(DBS)samplesfromexposed children aged 0–18 months, sent to Pasteur Institute of Cambodia from 8 maternities/pediatric services, were screened for thepresenceofDNAofHIV-1.(GenericHIVDNACell,Biocentric,Bandol, France). HIV-infected infants were referred to pediatricservices and follow-up.
Results: Since 2006, 925 HIV-exposed infants have been diagnosed on DBS. Fifty-five percent of pregnant women were on HAARTat time of delivery, 24% received AZT/sdNVP dual therapy, 10% sdNVPonlyand7%noprophylaxis(4%regimennotdocumented).Seventy-four percent of newborn received sdNVP plus AZT for one or 4 weeks, and 4% did not received any prophylaxis intervention (3%notdocumented).Forty-twooutof925werediagnosedHIV-infected including18/761newborngettingaccess toaveryearlyinfantdiagnosis(VEID)justafterbirth.Inuterotransmissionoccurredfor5/761(0.6%)(CI95%:0.21-1.53)andperpartumtransmissionfor 13/761 (1.7%) (CI 95%:0.91-2.91?). Only 3 newborns werebreastfeed. No postnatal transmission was detected. Among 42 HIVinfectedinfants,9diedand3werelostoffollowupbetweendiagnosis andHAART initiation, 26/42 startedHAART (4not yettreated).HIV-RNAviralloadsarealreadyavailablefor22/26afteratleast three months on HAART. HIV-RNA VL became undetectable for 11 of them, whereas 11 remain detectable. Among those, genotypingtestsrevealedthat7/8wereresistantto3TC/FTCandNVP/EFV. Three out of 7 harbored resistance mutation beforetreatment, 4 developing resistance after HAART initiation.
Conclusions:DespitetheprogressmadeinCambodiainthefieldof PMTCT and EID, access to the early infant diagnosis remains limitedatthenationallevel.Theseresultsconfirmtheveryhighriskof death in HIV-infected newborn in low-middle- incomes countries. These results also illustrate the difficulty of effectively treatingnewborn, who are at high risk to be in treatment failure.
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Earlydiagnosisoffailuretotreatmentinresourcelimitedcountries
Charles KOUANFACKCentral Hospital - Cameroon
L’accès au traitement antirétroviral a connu une progression spectaculaire dans les pays du Sud suite à la réduction des prix des traitements (InitiativeAccess) et sous l’impulsion initiale duprogramme 3by5 de l’OMS. Quand l’initiative « 3 millions d’ici2005»aétélancéeen2003,onestimaitque400000personnesdes pays à revenu faible ou intermédiaire suivaient un traitement antirétroviral [1]. Si la réalité de cet accès pour tous prendra encore de nombreuses années, compte tenu de l’ampleur des besoins etdesdifficultéspratiques,leprincipeestacquis:lespatientsduSuddoiventbénéficierdesARV,cequin’étaitpaslecasdanslesannées 2000.
Celaétant,enfin2008plusde4milliondepersonnes[4030000personnes;fourchette3700000-4360000]suivaientuntraitementantirétroviral ; un chiffre qui a été multiplié par 10 en cinq ans. La seule année 2008 a vu un accroissement annuel sans précédent du nombre de personnes sous traitement antirétroviral. En effet plus d’unmillion de personnes de plus qu’en 2007 étaient soustraitementenfin2008[2].
D’après les données de l’OMS, 98% de ces patients sous traitement sont sous protocoles de 1ère ligne. Selon la même source, seulement2%d’adulteset3%d’enfantssontsousprotocolesde2nde ligne et donc des protocoles contenant un anti protéase.
En Afrique du Sud, la probabilité cumulée de changement de traitementde1èreàla2ndeligneestde3à6%entroisans[3].AuMalawioùonaunsystèmedecollectededonnéesbienefficace,seulement518(0-3%)des145479patientsencoresoustraitementenfindécembre2008étaientpassésauprotocolede2ndeligne[4].AuCameroun,moinsde2%des76000patientssoustraitementenfin2009sontsousprotocolede2ndeligne.
La raison essentielle du faible diagnostic d’échec du protocole de 1ère ligne reste le manque de plateau technique adéquat. Il faut tout mêmenoter l’insuffisancedepersonnelenqualitéetenquantité,ladifficultéd’utilisationdescritèresde l’OMSpourdéfinir l’échec[5]. Par exemple, certaines pathologies classant stade 4 chez les patients sous traitement ne sont pas toujours synonymes d’échec (Tuberculosepulmonaire,maladiedekaposi)carpeuventsurveniravec un taux de CD4 élevé.
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Suite
Au Cameroun, nous avons mené une étude transversale dans un centre de traitement à Yaoundé. Dans cette structure comme dans beaucoup d’autres au Cameroun, les patients sont suivis selon l’approche de santé publique, ce qui signifie un bilan biologiquelimité. En effet, si au Cameroun la baisse progressive des prix des médicaments est passée à la gratuité depuisMai 2007, le bilanbiologique est subventionné en partie et surtout la charge virale resteentièrementàlachargedupatient.Autotal,249et178patientsrespectivement à 12 mois et 24 mois ont participé à cette étude. Les résultats montrent un taux de résistance de 4,4% des 249 patients (95%CI,2,2%-7,8%)à12moiset16,9%des178patients(95%CI,11,7%-23,2%)à24mois.Leconstatimportantdecetteétudeétait de voir que des 41 patients (56,9%) qui présentaient desrésistancessurles72quiontpuêtreséquencés,cetteproportionétaitde11/34(32,4%)à12moisetde30/38(78,9%)à24mois.Soit70%depatientsavecunechargeviraledétectableà12moisquin’ont pas encore de résistance alors que 80% qui ont une charge virale détectable à 24 mois ont déjà des résistances. Ceci remet en exergue la problématique du diagnostic tardif de l’échec de protocolede1èrelignedanslespaysàressourceslimitées.[6,7]
1-RapportOMS20043by5.http://data.unaids.org/GCWA/CGWA_BG_Treatment_fr.pdf2- Rapport OMS 2009 : http://www.who.int/hiv/en3-DaviesM-A,WoodR,VanCutsemG,etal.Virologic failureandsecond-lineantiretroviraltherapy(ART)inchildreninSouthAfrica:theinternationalepidemiologicdatabasestoevaluateAIDS(IeDEA)SouthernAfricacollaboration.Proceedingsofthe 5th Conference on HIV Pathogenesis, Treatment and Prevention; Cape Town, South Africa; July 19–22, 2009. Abstract MOAB1044- AIDS, Department of HIV and Ministry of Health, Quarterly report of theantiretroviral treatmentprogramme inMalawiwith resultsup to31stDecember2008, Ministry of Health, Lilongwe (2009) http://www.hivunitmohmw.org/Main/AntiretroviralTherapy/(accessedNov12,2009)5- BG Gazzard and BHIVA Treatment Guidelines Writing Group, British HIV Association guidelines for the treatment of HIV-1 infected adults with antiretroviral therapy2008,HIVMed9(2008),pp.563–6086- Prof Anthony D Harries MD et al. Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives(TheLancet2010)7-KouanfackC. et al. LowLevels ofAntiretroviral-ResistantHIV Infection in aRoutine Clinic in Cameroon that Uses the World Health Organization (WHO)Public Health Approach to Monitor Antiretroviral Treatment and Adequacy with the WHORecommendationforSecond-LineTreatment(1318•CID2009:48(1May)•HIV/AIDS)
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Lostoffollowupandresistanceemergence
Serge EHOLIEMinistry of Health - Ivory Coast
Abstract not provided
Session 2
Researchanddevelopment
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Novel CD4 technologies for monitoring anti retroviraltreatmentinsettingswithlimitedresources
Luc KESTENSInstitute of Tropical Medicine - Belgium
Since the start of the world-wide distribution of antiretroviral treatment in countries with limited resources, there is an increasing need for simple tests and technologies to monitor treatment efficacy (virus suppression, drug resistance) and to evaluate therestoration of the immune system (CD4 tests).Although reliablestate-of-the art technologies have been available for many years, theirwidedistributionhasbeendifficult.The reasons for thisarethat existing technologies were too complex, too expensive, require highly skilled technical staff and are often not robust enough. In theory, the solution seems simple: develop cheap and simple tests. In practice, the problem has been proven to be very complex and challenging. The presentation will give an overview of current and future generations of new point-of-care technologies for CD4 counting in resource limited settings the current.
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R&Dinvirologicaltests
Christine ROUZIOUXLaboratoire de Virologie, Hôpital Necker - France
HIV virological testing implementation is one of the highest priorities for HIV patients living in resource limited settings. Plasma HIV-RNA also called viral load, is the best tool to diagnose virological success, tore-inforceadherencetotreatmentandtosparefirstlinetherapyand unnecessary switch to second and third lines. Cell associated HIV-DNA that could be detected in blood cells, could also be an option developed for HIV diagnosis in babies born to HIV positive mother.Real-time PCR technology is now the most used and useful technology developed as it is quantitative, sensitive, reproducible and feasible in large series in automated systems. Systems adapted to short series are also available particularly as it may be needed in decentralised laboratories. At the moment, the market is dominated by four companies who developed automated closed systems. However, many examples of R and D are also developed by smaller suppliers, showing innovative systems and less expensive reagents. Many suppliers are in the starting blocks; they could participate to the implementation of viral load testing in different levelsof laboratories.As for instance, the first step thatincludes nucleic acid preparation could be achieved on different typesofmachineswithoutdifficult technicalassistance.Newrealtime PCR machines are also easy to use with the help of well driven software. In the context of research programs conducted in the South by TheANRS (Agence Nationale de recherches sur le Sida et leshépatites), we developed a viral load test commercialised byBiocentric (Bandol,France)whichrepresentsanexampleofnewtests. It is a sort of proof of concept for open systems as reagents may be used on different types of machines for both nucleic acid extraction and real time PCR. This test is adapted to a large majority of HIV-1 viral strains. It has been used in different ANRS sites for routine testing as well as for important clinical trials such as “Kesho Bora” in African countries and “Camelia” in Cambodia. Such open networks could also be very helpful as they may be used for other diagnosis such as HBV, HCV and tuberculosis.Point of care tests will be also available within next years. However, they won’t be adapted to large series, but much more for on-sites testing. They could be easily performed by technicians and/or nurses; semi quantitative results should help in some situations, such as HIV diagnosis in babies to help for rapid treatment initiation in infected ones. Again some innovative small systems are in the pipeline.
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Cost-effectiveness of viral load testing is now demonstrated by several groups as it might avoid resistance to ARV and may induce long-termefficiencyof thefirst linetherapy,preservingexpensivesecond and third lines of ARV. There is urgent need for new viral load tests, less expensive, easy to perform, reliable and sensitive. To open the market to new suppliers could help and facilitate innovative structures adapted to the context of each country. With the WHO recommendations, implementing HIV load is now one of the most important issues for people living with HIV.
Session 3
Strategies
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Earlydiagnosisininfants:biologicalaspects
Coumba TOURE KANECHU A Le Dantec - Senegal
Without treatment, HIV-infected children rapidly progress to AIDS, with about 50% dying before their second birthday. Early diagnosis ofinfectionandearlytreatmentcansignificantlyimprovethequalityof lifeandlifeexpectancyforHIV-infectedchildren.Inthefirst18months of life, infants carry the antibodies of their mothers, and thus cannot be accurately tested through traditional serological testing. Infants exposed to HIV are extremely vulnerable and consequently WHO recommendations call for early testing to identify HIV status If clinicians wait until infants are symptomatic to presumptively diagnose, critical time is wasted, and chances that the infant will survive decrease dramatically.
Infant diagnosis with DNA PCR, RNA PCR, or ultrasensitive P24 antigen testing can identify HIV in young infants, permitting life saving ,early care and treatment even before the presence of clinical or immunological symptoms. Molecular techniques required to identify the HIV status are not always available nationwide. So the development of good laboratory infrastructure and building up a cohort of trained technical staff are two pre-requisites for successful scale up in early infant diagnosis program. Dried Blood Spot (DBS)technologyallowssignificantdecentralizationofearlyinfantdiagnosis infants and both HIV DNA and HIV RNA technologies are becoming less expensive, more automated and faster in producing results.
Early virological diagnosis enables early identification of infantswho are infected and is the first step in securing their treatmentand care. It improves the psychosocial well-being of families and children, reducing potential stigma, discrimination and psychological distress for HIV-uninfected children. It facilitates also life-planning for parents and/or children who have HIV
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CurrentstatusofHIVincidencesurveillanceinPEPFARsupported countries, 2010
Andrea Y. KIMCenters for Disease Control and Prevention, USA
HIVincidenceisdefinedastherateofnewHIVinfectionsoveradefinedperiodoftime.HIVincidencecanbeusedtoappropriatelytarget prevention resources to those most vulnerable to HIV transmission, identify masked or missed sub-epidemics, closely monitor for the emergence of new sub-epidemics of HIV in the general population, and measure the impact of HIV prevention programs. Several approaches have been used for measuring level and trends in HIV incidence, including direct measurement in cohort studies, inference from HIV prevalence measurements in cross-sectional surveys using mathematical models, and a laboratory approach using tests for recent infection (TRI) in cross-sectionalsurveys; yet each presents specific challenges. The BED HIV-1incidence assay continues to be the only commercially available TRI and has been applied by various countries around the world to estimatepopulation-specificornationalHIV-1incidencebyapplyingthe assay to specimens derived from cross-sectional surveys with HIV testing. Although the BED assay has been used widely for incidence estimation, the assay has been found to overestimate population-level HIV-1 incidence due to a proportion of chronic HIV infections that misclassify as recent on the assay, in spite of years ofHIVinfection.Tocorrectformisclassification,theapplicationofstatisticaladjustmentsusingtheassay’sfalse-recentrate(FRR)isrequired.FRRsvarysignificantlybygeographicsetting; thereforecountries that plan incidence surveys must estimate a local FRR with similar characteristics to those in the incidence survey population, prior to estimating incidence. For example, if the incidence survey is to be conducted in a nationally representative survey, the FRR survey population should be nationally representative. Further, because of substantial misclassification rates among chronicallyinfected persons on ARV, both the false-recent survey and incidence survey should have the ability to detect individuals on ARV and subsequently exclude these cases from the incidence analysis. Countries should work with statisticians to ensure sample sizes for false recent rate surveys and incidence surveys are powered sufficientlytoprovidereliableestimatesofincidence.
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To overcome the limitations of the BED assay, new HIV-1 incidence assays with improved specificity and using different biologicalprinciples are being developed, namely avidity-based TRIs. The CDC has recently described a new avidity TRI using multi-subtype antigens. Additional work is ongoing to further characterize this assay and validate against other measures of HIV incidence. Commercial kits are in development and will be available to the public for pilot use by early 2011. In the absence of a nationally applicable gold standard for HIV incidence and pending the development of new laboratory-basedapproacheswithimprovedspecificity,countriesthatcontinuetouseTRIsshouldplantointerpretthesefindingsincombinationwith other available measures of incidence in the country and in conjunction with other epidemiologic. This synthesized approach can serve to validate the available incidence methods and produce more robust estimates of incidence in a population, than any one method alone
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IntegratingTB/HIVDiagnosticPlatformsinHighEndemicCountries
Giorgio ROSCIGNOFIND Diagnostics - Switzerland
Diagnosis and treatment of HIV and tuberculosis requires many laboratory services including rapid case detection, bio-monitoring of patients on anti-retroviral and antituberculous therapy, viral load testing and the drug susceptibility testing (DST) forTBandHIV.Programs for the major public health related diseases are still organized vertically as silos, addressing disease control, care and treatment separately and often competitively. This approach has resulted in the wasting of scarce resources due to the establishment of similar testing capacities for different diseases without common understanding and accountability. Therefore, strategies to integrate laboratory systems and services are essential to ensure sustainable and quality diagnostic testing across diseases.An integrated laboratory network should be able to provide all primary diagnostic services needed for care and treatment of patients without requiring them to go to different laboratory facilities for specific tests. The most promising approach to implementintegrated laboratory services is the establishment of integrated molecular diagnostic platforms since molecular testing can be used to rapidly detect and identify a wide range of viral and bacterial pathogens.One practical example of this model was piloted in the Kingdom of Lesotho. In 2008, the Lesotho National Tuberculosis Control Program (LNTCP) reported an incidence of 270 smear positivetuberculosispatientsfor100,000individuals(atotalof3862cases).TheLNTCPprognoses theemergenceofat least380multi-drugresistant (MDR) tuberculosiscases for2010. It isestimated thatnearly a quarter of Lesotho’s adult population is HIV positive. TheNationalTuberculosisReference Laboratory (NTRL) locatedatQueenElizabeth IIHospital inMaseru, thecapitalofLesotho,was renovated by the Foundation of Innovative New Diagnostics (FIND)andPartners inHealth toprovide capacity forTBcultureand molecular diagnostics. PCR-line probe assay based direct molecular detection of TB and MDR-TB was implemented in the routine in 2008 and after streamlining the new TB molecular diagnostic services the unit was evaluated for additional molecular testing capacity not avilable in the country yet.
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Until2008specimensforearlyinfantdiagnosis(EID)HIVDNAPCRwere submitted to South Africa for routine testing. This approach was time consuming and expensive due to transportation related delays and inconclusive results due to compromised specimens. Therefore, during the summer of 2009 molecular testing of dried bloodspot(DBS)specimensforEIDwasalsoimplementedatthenewly established TB molecular unit using the same personnel and equipments resulting in the establishment of integrated TB/HIV testing in a single facility. In 2009 and 2010 the laboratory alsosusccessfullycompletedthefirstEIDEQAeventsprovidedbythe Global AIDS Program at the Centers for Disease Control and Prevention. Following an integrated approach, implementation of novel molecular TB diagnostics paved the way to introduce HIV moleculartestingcapacityinthecountryandsignificantlyreducetheturnaroundtimeoftesting.Thisapproachisoneofthefirstexamplefrom Africa on improving diagnostic services in an integrated fashion.TherecentlydevelopedGeneXpertRif(Cepheid)walkaway,real-time PCR based assay opens an novel path on integrated disease testing by molecular platforms. Compared to LPA this test doesn not require labours specimen preparation under special biosafety restrictions, fast and simple to perform. Therefore, it can be implementedatlower(regionalordisrtict) levelsofthediagnosticnetwork. A viral load testing application by this system is under development.Similarly,theisothermalLAMP(Eiken)systemoffersa manual but easy to perform closed system for both the rapid molecular detection of TB and early infant diagnosis of HIV.
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Quantification of HIV viral load to assess the need toswitchtosecondlineantiretroviraldrug.ExperiencefromthepublicsectorinMyanmar.
Philippe CLEVENBERGHInternational Union Against Tuberculosis and Lung Disease - Myanmar
Background: First line therapy failure is often diagnosed late. WHO immunologicand/orclinicalcriteria lackspecificityandsensitivity.QuantificationofHIVviralload(VL)helpsdiagnosetreatmentfailu-re while avoiding unnecessary switches to costly 2nd line drugs. VL testing should be targeted to patients most likely to fail as it is barely available and expensive.
Aim: to describe the use of VL testing to assess the need for second line drugs according to WHO criteria.
Methods: Charts of patients having a VL measured were extrac-ted for demographic, clinical and biological variables, antiretrovi-raltreatment(ART)experienceandoutcomes.Theseparameterswerecomparedinpatientswithdetectable(failing)andundetecta-ble(successful)VLusingχ2.
Results:90(61males/29females)patients,meanage:32years,hadaVLmeasured.VLwasdetectedin51(57%)patients(mean:5.65(2.7-6.6) log10cp/ml).MedianbaselineCD4countwas137cells/µlinfailingpatientsversus117cells/µlinsuccessfulpatients(p=ns).A newOI was diagnosed in 12/51 (23%) failing patientsversus1/49(3%) insuccessfulpatients(p<0.05).FailingpatientsreceivedART foramedian35 [28-44]monthsversus24 [17-38]months for successful patients (p<0.05).Twenty three failingpa-tients versus 6 successful patients were treated in private practice (p<0.05).Threemonthsoutcomeisalive:32(82%)patients,dead:5(13%)patients,defaulters:2(5%)patientsamongfailingpatients,andalive:28(88%)patients,dead:2(6%)patients,defaulters:2(6%) patients among successful patients, respectively. In 35/51(67%)failingpatientssecondlinewasstarted.MeanCD4increaseafter3monthsis105(12-281)cells/µl.
Conclusion: Fifty-seven percent of tested patients have detectable VL. Failing patients are diagnosed late and have a poor outcome even when switched to second line drugs. In multivariate analysis, new OI and a history of private practice are predictive of failure.
Session4
Healthcaresystemstrengthening
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Point-of-carestrategiesandinnovativetechnologies
Wendy STEVENSNational Health Laboratory Service - South Africa
Point- of- care (POC) testing performed at or near the patient bedside is increasingly being used to improve the turnaround time of laboratory results and improve accessibility to care. This has particular relevance in resource- limited settings and for the management of chronic diseases such as HIV and tuberculosis. Rapid technological advances in the last decade have facilitated this approach for more sophisticated assays such as CD4 and molecular based tests for M. tuberculosis(includingRifampinresistance)andHIV. Common themes in research and development facilitating this technologicalexpansionincludethedevelopmentofmicro-fluidicsfor fluid delivery, miniaturization and low cost micro-fabrication,thedevelopmentofefficient,inexpensivelightsources,affordablemicroelectronics, digital imaging hardware, simplified powersourcesandelectromagneticactuationoffluidsusingmicro/nanoelectronics. The cited advantages of POC testing include improved turnaround time, greater accessibility, potentially improved patient retention and possible reduction in overall health care costs . In the South African primary healthcare environment and in other resource limited settings, POC assays should meet at least the following specifications: 1) be rapid with generation of resultswithinthetimeoftheconsultation,2)requireminimaltraining,3)beeasytoperform,4)requirenospecializedlaboratorysetupand5)reagents should be stable and temperature independent. It should also be noted that while certain POC assays generate results that are equivalent to central processing facilities, certain assays do not and thus there remains a need for ongoing vigilance and method validation. Various authors have highlighted the need for external quality assessment from a central laboratory and laboratory training for clinical staff. The transfer of assays from a centralized testing facility to POC does not ensure improved clinical outcome and the value needs to be proven in properly controlled clinical studies. The need for centralized data monitoring and the ability to interface with information systems needs to be taken into consideration. Unless this aspect is addressed, once the clinician views the results at the time of testing, they may no longer be available for other healthcare providers. Once POC testing is implemented there has to be assurance that data can still be audited and managed.
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While being hailed as the solution for many settings and medical conditions, the implementation of POC testing needs to be done cautiously to ensure appropriate management of quality assurance, clinic resources and data collection. These issues have previously arisen with large- scale implementation of HIV rapid testing strategies which remain a challenge in many countries, including South Africa. Local experience will be presented with respect to technologies available and clinical validations conducted for implementation of POC testing strategies.
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Capacitybuildingindiagnosticservices
Souleymane MBOUPUniversité Cheikh Anta Diop, Sénégal
African countries continue to carry the brunt of the world’s major infectious disease problems such as HIV, TB, malaria and respiratory infections and must also face the growing challenge of non-communicable diseases. These disease burdens undermine the economic growth and prosperity of these nations by reducing productivity and life expectancy and putting strains on local health services.
Laboratory services, networks and systems are indispensible to effective well-functioning health systems. High quality laboratory testing is vital for effective patient care, prevention, disease surveillance and outbreak investigations. In sub-Saharan Africa, laboratory infrastructure and personnel have long suffered from neglect and lack of resources, hampering laboratory systems from fulfillingtheircriticalroleinthefightagainstinfectiousandchronicdiseases. As a result, the accessibility of laboratory testing and the quality of available services remains a serious challenge. It is therefore imperative that laboratory systems be strengthened as partofbroaderhealthsystemstrengthening(HSS)efforts.
The need to further develop encouraging and favourable environments within our health institutions in Africa is well recognized. These will provide the basic incentives required to build critical numbers of African scientists and allow them to stay within the sub-region and develop productive careers. It is therefore necessary to invest in strengthening areas that support diagnosticservicesbytraininginefficientadministrativesupport ,byincreasingthecapacityforefficientoperationsofthelaboratoriesand the advanced instruments that scientists depend on to fulfilltheir work, , and also by establishing and maintaining fast internet information services
Laboratory quality management systems (for implementationofGCLP)will ensure theoptimaluseof laboratory resources forthe attainment of improved results and will ensure that the data generated meets international standards.
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HealthcareinAfricawillnotbenefitfullyfromresearchuntilthereisa critical mass of indigenous researchers who work at the local level and have unique insights into what new interventions are needed and how they can be delivered effectively.
Increasing the numbers of highly trained and skilled researchers who will lead globally competitive, collaborative health research requires well-equipped, enabling environments with incentives to stimulate the contributions and sustain the efforts of African researchers. This can be achieved by supporting a long-term, sustainable consortium of African and international partners willing to pool expertise and utilize their on-going research activities for the professional and personal development of young African researchers.
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ImprovingthefollowuptreatmentofHIV/AIDSpatients:Implementation of HIV-1 Viral Load (VL) testing at theCentreChristopheMérieuxofLaoPDR
Phimpha PABORIBOUNECentre Christophe Mérieux - LAO PDR
In 2009, the HIV prevalence in Laos, a country with 6.5 million inhabitants, was estimated at 0.3% among adults (> 15 years).Currently, it is estimated that more than 12,000 people are living with HIV. The opening of the borders with neighboring countries (China, Thailand, Vietnam, and Cambodia) could increase theinfection rateof the country.ThefirstHIV/AIDS treatment centerwascreatedbyMSFin2003,inthesoutherncityofSavannakhet.Sincethen,sixothercentershavebeencreated:2inVientiane,3inthenorthand1inthesouth.ThankstoCHAS(CenterforHIV/AIDS/STI),financedbytheGlobalFund,thenumberofpatientsreceivingARVtreatmentisestimatedat1,400in2010.ThefirstandsecondlinetreatmentsavailableinLaosare:D4TorAZT+3TC+NVPthen3TCorFTC+TDF+ATV/rorLPV/rrespectively.Thenewtreatmentrecommendations from CHAS, published at the end of 2009, state thattheARVtreatmentshouldbeginatCD4≤350/mm3,orfortheWHOclinicalstage3or4irrespectiveoftheCD4count.PriortoJuly2009,whenHIVViralLoad(VL)testingwasimplementedattheCentreChristopheMérieuxofLaoPDR(CCML),locatedinVientiane, VL testing was not possible in Lao PDR. This made it difficulttofollowuppatientsreceivingARVtreatmentandimpossibleto diagnose babies between 6 and 18 months. Sometimes, tests were performed in Thailand, but this was very expensive and required complex logistics. Consequently, the number of patients receiving ARV treatment and proper follow up was limited.Originally, the implementation and use of the VL technique was planned to take place in Mahosot Hospital, as part of the ESTHER program, which has established two HIV/AIDS treatment centers in Lao PDR; Mahosot Hospital in Vientiane, and Luang Prabang in the north. Unfortunately, the lack of appropriate infrastructure and human resources made this project impossible to realize as planned. Therefore, ESTHER and other partners including CHAS, WHO, Pasteur Institute and Mérieux Foundation collaborated to implement this testing at CCML. The technique used comes from theANRS:Quantificationof theplasmaticARNHIV-1,Biocentric,Bandol, France.
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From May 2009 to July 2010, the different steps have been the following:1)TechnologicaltransferfromthePasteurInstituteofCambodiatoCCML.2) Implementation of the quality control procedures inter/intralaboratories and external.3)Creationofanationaldatabaseforthetreatmentsfollowupandthe virological failure. 4)Organizationof twonationalworkshops for thedoctors of thetreatment centers, including a discussion on sample shipments, result reporting, result interpretation, and the follow up of all patients receivingARVtreatmentwithafirstdetectableVLtest.As of July 2010, VL testing has been performed for 589 patients fromallHIV/AIDStreatmentcenters.Theaverageageis36,withamale to female ratio of 1.2:1. Among them, 458 are receiving ARV treatment, which represents 34.6% of all the patients receivingARVtreatment inthecountry.96%(n=465)areunderfirst line(amajorityD4T+3TC+NVPorEFV)and4%(n=20)undersecondline treatment.Theaverage lengthof treatment is3years (Min.:5months,Max.:7years).19.4% (94/458)showadetectableVL(average:5log),3ofwhichareundersecondlinetreatment.Amongthe94patientswithafirstdetectableVL test, 43.6% (41/94)didasecondtest. 17%(7/41)of thesewerestilldetectablewith thesecond test. 30.8% (29/94)arestill less than3monthsafter thefirstVLtest.Detailedanduptodateresultsoftheanalyseswillbepresented.The implementation of a national follow up of the patients receiving ARV treatment using the VL measurement is now possible in Lao PDR,withthefinancialsupportoftheGlobalFundandESTHER.This enables the follow up of the failure of ARV treatment, as well as a diagnostic test for children between 6 and 18 months. After a year of implementation of VL testing, the results show the need for implementation of tools to study resistance genotyping.
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Strengthening laboratory systems in developingcountries:Implementingpracticalandaffordablequalitymanagementsystems
John NKENGASONGCenter for Global Health - CDC Atlanta - USA
Thelastfiveyearshaveseentremendousincreasesindevelopmentfunding for global health, with an estimated $22 billion available in 2007alone.Withincreasedfunding,strengtheninghealthsystems,toensureefficientmanagementofintegratedandcomprehensiveservices for diseases of public health importance has taken center stage. Quality laboratory services and systems constitute thefoundation for strengthening health systems as the primary goal of laboratory medicine is to provide information that is critical to assist medical decision-making for the best healthcare. However, few countries in developing countries have established laboratory standards that are affordable and easy to implement and monitor. To address this challenge, in April 2008 (Lyon, France), WHOand theU.S.Centers forDiseaseControlandPrevention (CDC)issued a statement regarding laboratory quality systems, calling for countries with limited resources to consider a staged approach toward laboratory accreditation. It was suggested that principal requirements be stated in national laboratory standards as minimum requirements for all laboratories, while more advanced and national reference laboratories were encouraged to meet internationally accepted standards, such as ISO 15189; In keeping with its core functions to set standards and norms and assist countries to implement them, theWorld Health Organization Regional OfficeforAfrica(WHO-AFRO)hasestablishedanapproachthatprovideslaboratorieswithstepwiserecognitionofevolvingfulfilmentoftheISO 15189 standard rather than binary pass/fail grading. Assessed laboratorieswillberecognizedonazerotofivestarascendingscale.WHO-AFRO’s accreditation process is not intended to replace established ISO 15189 accreditation schemes, but rather provide an interim pathway to the realization of international laboratory standards. We believe that the WHO AFRO approach for laboratory accreditation is affordable, sustainable, effective, and scalable. In its deliberations, WHO-AFRO considered many models, including affordable and effective approaches implemented in other regions. For example, between 2002 and 2009, Thailand developed national standards based upon ISO 15189 and the Thailand Medical Technology Council assessed 50% of the country’s 1400 clinical laboratories.
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The Thai system frames laboratory performance in four levels of demonstrated conformity to the Thai standards. Of the 724laboratories assessed to date, 27% (197) have been accreditedasfullycompliant,whiletheother73%oflaboratoriesvisitedhavescored70%orhigheronassessmentandcontinuetoworktowardthe highest rating. In Argentina, in 1994, Fundacion Bioquimica Argentina (FBA) established national minimum standards andassessed laboratories accordingly, subsequently developed a more demanding standard and also implemented it. In the last 15 years FBAhasconductedover7000laboratoryassessmentsandboasts1100 accredited laboratories in 19 of Argentina’s 24 provinces. All Argentina’s1200clinicallaboratorieshadsuccessfullyfulfilledtheprogram requirements.
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Procurement in the perspective of the ClintonFoundation
Trevor PETERClinton Foundation - USA
Over the past ten years the challenges to the procurement and supply chain of diagnostic products for essential health services in resource-limited settings have changed. Initially, high cost was the primary barrier and subsequent negotiation, volume-based discounts and partnerships with diagnostics manufacturers led to substantial reductions in the cost of diagnostic equipment and commodities, especially for HIV-related testing. The scale of testing increased dramatically and this has placed new pressures on health care systems. More recently the operational challenges of ensuring efficient and reliable supply of essential diagnostic products hasbecome the greater bottleneck to the delivery of diagnostic services for major diseases in resource-limited settings. It is increasingly importanttoimprovetheefficiencyofservicedeliveryandimproveddiagnostics supply chain management may lead to substantial cost savings.Most tests require multiple products from different manufacturers which are used at different rates and which may have different shelf-lives. Often reagents require cold chain. Many laboratory products are specialized and are not true commodities. Hence, diagnostic supply chain is more complicated than drug supply chain, yet limited expertise for diagnostics procurement exists in most settings. Frequently, laboratory experts are not involved in settingspecificationsandquantitiesor inmanagingsupplychain.Theresultofthesedifficultiesiswellknown:stock-outsandover-supply are common, leading to inconsistent testing services and potentially poor patient outcomes.The strengthening of procurement and supply chain systems is essential and underway in many countries. For example capacity for improved forecasting and inventory management is being established using improved tools. Standardization of testing networks as recommended by the Maputo Declaration of 2008 is also being implemented. In addition, there may be novel opportunities to simplify supply chain management through the greater use of bundlingofessentialproductsforspecifictestsandtheuseofGSMor GPRS technology to track consumption. Lastly, the migration towards new, simpler point of care diagnostic systems as well as to high volume testing depots offers both advantages and challenges to supply chain.
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DREAMexperience
Giovanni GUIDOTTIDream Project - Italy
Clinicalexperiencehasdemonstratedtheunquestionablebenefitoflaboratory support in the diagnosis and monitoring of patients with HIV infection. One remaining issue where expert opinions diverge is the cost-benefit usefulness of laboratories in countries withlimited resources. Clinical experience demonstrates a beneficialeffect in terms of patient survival and effective use of resources in research programmes that include routine use of CD4 lymphocyte counts and viral load determination in the monitoring and treatment of patients. The DART study reported an advantage in terms of patient survival, particularly in patients with CD4 counts above 200 permm3,whoseswitchtosecondlinetreatmentwasguidedbytheuse of laboratory assays. This is of critical importance in light of the new WHO treatment guidelines which recommend initiation of antiretroviral treatment for individuals with CD4 cell counts below 350.ArecentstudybyKimmeletal.concludedthat“..Inresource-limited settings, CD4 count and HIV RNA monitoring to guide switches to second-line ART improve survival and, under most conditions, are cost-effective”.
The DREAM programme has included routine CD4 cell count assessments and quantitative viral load determination in the monitoring of patients with HIV infection since its inception in 2001. At present the programme runs 14 laboratories in 10 African countries.Based on nearly 10 years ofworking in the field, it isour experience that with the centralization of specific laboratoryservices(particularlymolecularbiology),ahandfulof laboratoriescan provide effective monitoring to thousands of patients with a minimalturn-aroundtimeofresults(15-21days)atacostof lessthan 40 USD per year. This cost can be further reduced if the test volume is high, due to a simple economy of scale effect.
.An analysis of data from our DREAM programme in Malawi provided evidence of the usefulness of laboratory monitoring in patients with HIV infection. An immediate application to laboratory monitoring is the decision of when to switch patients to second line antiretroviral regimens. Clinical monitoring alone has been shown to lead to excess mortality as compared to laboratory and clinical monitoring combined, especially in patients with CD4 cell counts over200cells/mm3.ExclusivemonitoringofCD4subsetsasthesingle laboratory parameter has also not been shown to be effective as patients accumulate resistance mutations while the viral burden is unmonitored before the ineffectiveness of therapy becomes clinically apparent.
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The use of exclusive viral load monitoring without CD4 cell count assessments may lead to unnecessary switches in therapy and an increase in costs.
Aretrospectiveanalysisofrecordsfor1,076adultpatientswhowerefollowedatDREAMcentres inMalawibeforeDecember312007was performed. . An assessment of CD4 cell counts and viral load at baseline, 6, 12, 18 and 24 months was conducted. All analyses were performed at DREAM laboratories in Malawi. After six months of treatment 9% of the patients would have to switch to a second line regimen because they failed to reach a viral load lower than 400 c/ml. According to the six month CD4 count assessments most of these patients did have a partial response to HAART since their CD4 cell counts increased by more than 10% of pre-HAART values. At least one third of these patients reached an undetectable viral load by the 12 month time point. The unnecessary switch of these patients to a second line regimen at 6 months based on viral load monitoring alone would cost about 40 times more than performing a CD4 cell count and 4 times more than performing a routine CD4 count per year for all patients receiving HAART.
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Fieldexperience:AccordiaFoundation - InfectiousDiseasesInstitute
Yuka MANABEAcoordia Foundation - Uganda
Accordia Global Health Foundation through the Infectious Diseases Institute has participated in the full continuum of HIV diagnostics from research, clinical core laboratory validation, and fieldimplementation.ThroughtheUSNationalInstitutesofHealth,TB diagnostics are currently being tested. Validations of clinical algorithms have also been done at the Makerere University-Johns Hopkins University Clinical core lab at the IDI (e.g. sequentialcomparedtotheparalleltestingfortherapidHIVtests).Finally,fieldimplementation of malaria smear testing and rapid testing has been pioneered at the IDI through the Joint Ugandan Malaria Program (JUMP).Throughthisprogram,healthcenterteamsaretrainedina multidisciplinary on-site training. Innovative post-training on-site supervision has been employed for sustainable, high quality testing thatinfluencesclinicaldecisionmaking.Suchtrainingallowshealthprofessionals to move from empiric algorithm based treatment to rapidtest-confirmeddiagnoseswithtargetedcurativetreatment.
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Speakers Avelin Aghokong [email protected] IRD
Isabelle Andrieux-Meyer [email protected] Médecins Sans Frontières
Laurent Belec [email protected] Hôpital Européen Georges Pompidou
Deborah Birx [email protected] CDC
Gilles Brücker [email protected] ESTHER
Steven Buchsbaum [email protected] Bill & Melinda Gates Foundation
Alexandra Calmy [email protected] Geneva University Hospital
Pascale Chaillet [email protected] Médecins Sans Frontières
Philippe Clevenbergh [email protected] The Union
Robert Colebunders [email protected] Institute of Tropical Medicine
Paul De Lay [email protected] UNAIDS
Patrice Debré [email protected] Ministère des Affaires Etrangères
Jean François Delfraissy [email protected] ANRS
Serge Eholié [email protected] Ministry of Health Pierre Marie Girard [email protected] APHP
Julian Gold [email protected] WHO Collaborating Center for HIV
Gianni Guidotti [email protected] Dream Project
Catherine Hankins [email protected] UNAIDS
Hakima Himmich [email protected] ALCS
Luc Kestens [email protected] Institute of Tropical Medicine
Andrea Y. Kim [email protected] CDC
Charles Kouanfack [email protected] Central Hospital
Christian Laurent [email protected] IRD Jean Elie Malkin [email protected] UNAIDS
Speakers
Yuka Manabe [email protected] Foundation
Souleymane Mboup [email protected] Cheikh Anta DIOP
Benoit Miribel [email protected] Fondation Mérieux
Eric Nerrienet [email protected] Institut Pasteur
John Ngenkasong [email protected] CDC
Phimpha Paboriboune [email protected] Christophe Mérieux
Martine Peeters [email protected] IRD
Trevor F. Peter [email protected] Clinton Foundation
Dominique Peyramond [email protected] Lyon
Praphan Pranupak [email protected] Thai Red Cross
Gilles Raguin [email protected] ESTHER
Giorgio Roscigno [email protected]
Christine Rouzioux [email protected] APHP
François Simon [email protected] APHP
Wendy Stevens [email protected] National Health Laboratory Service
Coumba Touré [email protected] University Cheikh Anta DIOP
Marco Vitoria [email protected] WHO - HIV
Participants
Eric Atin [email protected] bioMérieux
Veronique Baron-Wunderle [email protected] bioMérieux
Rui Bastos [email protected] MoH
Brigitte Bazin [email protected] ANRS
Emilio Brignoli [email protected] bioMérieux
Natalie Cartwright [email protected] Global Fund
Philippe Creach [email protected] Global Fund
Siobhan Crowley [email protected] UNICEF
Jean-François Etard [email protected] Epicentre
Jean-Chrysostome Gody [email protected] Faculty of Health Sciences
James [email protected] University of Zimbabwe
Bradley Hersh [email protected]
Florence Huber [email protected] SOLTHIS
Christine Katlama [email protected] Hôpital Pitié Salpétrière
Silvia Klebert [email protected] ICAP
Marc Leportier [email protected] bioMérieux
Christophe Longuet [email protected] Fondation Mérieux
Sophie Matheron [email protected] Hôpital Bichat
Claude Moncorgé [email protected] OPALS
Josette Najjar [email protected] Fondation Mérieux
Théodore Niyongabo [email protected] HIV National Reference Center
Patrick Njukeng [email protected] GHSSCMR - Global Health Systems Solutions
Valentina Picot [email protected] Fondation Mérieux
Meja Rabodonirina [email protected] CHU Lyon
Participants
Judith Shang [email protected] Shemka Foundation
Mariangela Simao [email protected] UNAIDS
Nicolas Steenkeste [email protected] Fondation Mérieux
Vincent Turbat [email protected] World Bank
Guy Vernet [email protected] Mérieux
