Achieving sustainable development goals for HIV/AIDS in the Republic of the Congo - Progress, obstacles and challenges in HIV/AIDS health services

Review

Achieving

sustainable

development

goals

for

HIV/AIDS

in

the

Republic

of

the

Congo

—

Progress,

obstacles

and

challenges

in

HIV/

AIDS

health

services

Laure

Stella

Ghoma

Linguissi

,

Violaine

Lucaccioni

,

Matthew

Bates

,

Alimuddin

Zumla

,

Francine

Ntoumi

*

a

InstitutNationaldeRechercheenSciencesdelaSanté(IRSSA),Brazzaville,Congo

b

FondationCongolaisepourlaRechercheMédicale(FCRM),Brazzaville,Congo

c_{CliniqueLaennec,Malakoff,France} d

SchoolofLifeSciences,UniversityofLincoln,Lincoln,UK

e

CentreforClinicalMicrobiology,DivisionofInfectionandImmunity,UniversityCollegeLondon,UK

f

NIHRBiomedicalResearchCenteratUniversityCollegeLondonHospitalsNHSFoundationTrust,London,UK

g

FacultyofSciencesandTechniques,UniversityMarienNgouabi,Brazzaville,Congo

h

InstituteforTropicalMedicine,UniversityofTübingen,Tübingen,Germany

ARTICLE INFO

Articlehistory: Received27June2018

Receivedinrevisedform11October2018 Accepted11October2018

Corresponding Editor: Eskild Petersen, Aarhus,Denmark Keywords: HIV AIDS ARV HAART Coverage Impact Treatment

RepublicoftheCongo

ABSTRACT

TheHIVepidemiccontinuestobeamajorglobalpublichealthissue.Since2012,therehasbeenapaucity ofinformationfromtheRepublicoftheCongoonHIVincidenceandprevalencerates,nationalHIV programme effectiveness,highlyactiveantiretroviraltherapy(HAART)rollout,patientadherenceto treatment,operationalandbasicscienceresearchstudiesonHIV/AIDS,anddonorfundinganditsimpact onthecountry.AreviewoftheexistingliteratureonHIVintheRepublicoftheCongowasconducted, focusedonprevalencetrends,effectivenessofthecurrentnational HIVprogramme,HAARTrollout, patientadherencetoantiretrovirals(ARVs),resistancetoARVs,thecostoftreatment,andoperational issuesaffectingHIV/AIDSprogrammesinthecountry.Inlightofthefindings,severalimportantpriority areasforscaling-upHIV/AIDSservices,programmaticandresearchactivitiesintheRepublicoftheCongo arehighlighted.

CrownCopyright©2018PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectious Diseases.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/). Contents Introduction ... 108 Methods ... 108 Results... 108 Discussion ... 108

DevelopmentofthenationalpublichealthresponsetoHIV ... 109

Cascadeofcareandmanagementissues ... 109

Adherence ... 109

Optimizingandmonitoringtreatment ... 109

ResistancetoARVs ... 110

Mother-to-childHIVtransmission ... 110

Co-trimoxazoleprophylaxis ... 110

ExternalfundingfortheHIV/AIDSprogrammeintheRepublicoftheCongo ... 110

* Correspondingauthorat:FondationCongolaisepourlaRechercheMédicale (FCRM),Brazzaville,Congo.

E-mailaddress:[email protected](F.Ntoumi).

https://doi.org/10.1016/j.ijid.2018.10.009

1201-9712/CrownCopyright©2018PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

ContentslistsavailableatScienceDirect

International

Journal

of

Infectious

Diseases

ARVsupplychainandqualityofdrugs ... 110

PrioritiesforHIV/AIDSprogrammestrengtheningintheRepublicoftheCongo ... 111

Acknowledgements ... 111

References ... 111

Introduction

TheHIVepidemiccontinuestobeamajorglobalpublichealth issue.In2017,therewere25.7millionmen,women,andchildren livingwithHIV/AIDSinSub-SaharanAfrica,accountingfor two-thirdsoftheglobaltotalofnewHIVinfections(UNAIDS,2018). TheJointUnitedNationsProgrammeonHIV/AIDS(UNAIDS) Fast-Track strategyaims to increasethe HIV response in low- and middle-incomecountries toendthe epidemicby2030 (Sidibé etal.,2016).ThiswillrequirecountryHIVprogrammestodetect andtreat allpeoplelivingwithHIV/AIDS(PLWHA)withhighly activeantiretroviraltherapy(HAART),sothattheHIVviralload reducestoalevel wheretheHIV-infectedpersonis unlikelyto transmitHIV to others, thus curtailing the transmission cycle (WHO,2015).CurrentWHOfigures estimatethatin2017there were17millionPLWHAwhowerereceiveingHAARTworldwide (UNAIDS,2018).

TheRepublicoftheCongo(RoC)hasapopulationofnearlyfive million,and life-expectancyatbirth was 63 yearsin 2016.The SecrétariatExécutifPermanent/ComitéNationaldeLutteContrele SIDA(SEP/CNLS)isresponsibleforcoordinatingtheNationalHIV response.AnotificationsystemforHIV/AIDScasesdoesnotexistin RoC,thereforetherearenoaccurateandreliableepidemiological, clinical,andmanagementoutcomesdataonHIV/AIDS.DataonHIV prevalence in RoC are scarce and come indirectly from small individualstudies.ThepointprevalenceofHIVinfectionin Pointe-Noirewas 14%in2000and5%inBrazzavillebetween1996and 2000.TheHIVprevalenceinsexworkerswas34.3%inBrazzaville and64.1%inPointe-Noire(UNAIDSandWHO,2004).In2012,an HIV-relatedbehaviouralsurveyofsexworkers,menwhohavesex with men (MSM), and prisoners in four locations across the country(Cuvette-Ouest,Plateaux,Pool,andLékoumou),foundHIV prevalenceof 3.2%in thegeneralpopulationaged15–49years, whichwasslightlyhigherinurban(3.3%)thaninruralareas(2.8%). TheHIVprevalenceamongMSMwas26.1%andamongsexworkers was 7.5% (WHO Regional office for Africa, 2006). The HIV prevalence of 8.3% among prisoners was higher than in the generalpopulation(WHORegionalofficeforAfrica,2006).

Since2012,therehasbeenapaucityofinformationfromRoCon HIV incidence and prevalence rates, national HIV programme effectiveness, HAART rollout, patient adherence to treatment, operationalandbasicscienceresearchstudiesonHIV/AIDS,and donor fundingand its impact onthe country. A review of the existingliteratureonHIVinRoCwasthereforeconducted,focused ontheprevalencetrends,effectivenessofthecurrentnationalHIV programme,HAARTrollout,patientadherencetoARVs,resistance toARVs, thecost oftreatment, and operationalissuesaffecting HIV/AIDSprogrammesinthecountry.Severalimportantpriority areasforthepublichealthresponsetoHIVinRoCarediscussedin lightofthestudyfindings.

Methods

ReportsandpublicationspublishedinEnglishandFrenchwere identi_fiedthroughasearchofthePubMeddatabasecoveringthe periodSeptember1,1995–September1,2017usingthekeywords ‘Congo’or‘RepublicofCongo’withtheterms‘HIV’and‘AIDS’and combinations with ‘incidence’; ‘prevalence’; ‘HAART’; ‘ARV’; ‘rollout’; ‘treatment’; ‘toxicity’; ‘side effects’; ‘adherence’; ‘HIV

program’;‘AIDSprogram’;‘PLWHIV’;‘HIV-infected’;‘Sexworkers’; ‘gender’; ‘donor’; ‘HIV research’; ‘AIDS research’; and ‘funding’. SearchresultsthatwerefoundtoberelevanttoHIVinRoCand Africawereselectedforthisreview.Otherstudiescitedinarticles identifiedinthesearchesthatwererelevanttoHIVinAfricaand RoCwerealsoreviewed.InternalreportsonHIV/AIDSpublishedby RoCnationally;andreportsbyexternalagenciessuchastheWHO; UNAIDS;Unitaid;andtheGlobalFundtoFightAIDS;Tuberculosis andMalaria(GlobalFund)relatedtoHIV/AIDSinAfricawerealso reviewed.

Results

Eighty publications were identified through the search (Figure 1). Fifty-nine articles and publications that were not relevanttoRoCwereexcluded.Furthermore,publicationsfromthe DemocraticRepublicoftheCongo(DRC)wereexcluded,asDRCisa differentcountryandappearedfrequentlyinthesearchduetothe similarityofnames.AfurtherfivearticlesthatmentionedRoCbut were not relevant to HIV in RoC were also excluded. Thirteen publications wereselectedfor thefinalanalysis, ofwhicheight werePubMed articles,threewere RoCnational reports,and 10 were reports from global health agencies such as the WHO, UNAIDS, UNITAID, and the Global Fund. This review of the literatureconfirmed thepaucity of data onHIV in RoC. Of the 80articlesidentified,therewereonlyeightarticlesinthePubMed databaseandthreeRoCgovernmentreportsrelevanttoHIVand HAART in RoC. The absence of an effective notification, data collectionandreportingsystemforHIV/AIDScasesinRoChasled toapaucityofaccurateandreliableepidemiological,clinical,and managementoutcomesdataonHIV/AIDS.

Discussion

In lightofthepaucity ofdataavailable intheliterature, the discussionisfocusedonHIVprevalencetrends,theeffectivenessof the current national HIV programme, HAART rollout, patient adherencetoARVs,resistancetoARVs,thecostoftreatment,and operational issues affecting HIV/AIDS programmes in RoC. The priority needs for further development of the national public healthresponsetoHIV,improvingthequalityandquantityofthe cascade of HIV care, and taking forward current priorities for

strengthening of the HIV/AIDS programme in RoC are also discussed.

DevelopmentofthenationalpublichealthresponsetoHIV

InMarch2006,RoCcommittedtotheBrazzavilleCommitment onscalinguptowardsuniversalaccesstoHIVandAIDSprevention, treatment, care, and supportin Africa by2010 (WHO Regional officefor Africa,2006).Thiswas formulatedbytheContinental Consultation on Scaling up towards Universal Access in Africa convened by the African Union (which represents 53 African MemberStates)withsupportfromtheWHO,UNAIDS,Economic Commission for Africa (ECA), and the UK Department for InternationalDevelopment(DFID)andwithrepresentativesfrom governments, parliaments, civil society, PLWHA, faith-based organizations,andtheprivatesectorfromthe53MemberStates oftheAfricanUnion.AnambitiousinitiativeforreducingtheHIV/ AIDSburden in RoC in 2008 recommended free healthcare for PLWHA,includingdiagnostictests,HAARTtreatment,and follow-up(LNSP,2012).In2011,legislationcalled“LuttecontreleVIHetle SIDA,etpourlaprotectiondesdroitsdespersonnesvivantavecle VIH”wasintroducedtosupporthealthcareforPLWHAtoprevent recurrenceofthefrequentshortagesofARVsthatoccurredduring the establishment of the Congolese Access to Antiretroviral Initiativebetween2004andlate2006.

From2004to2005,afeeofbetween6.68USDand66.80USD waschargedtothepatientforHAARTmedicines,theexactamount dependingon thepatient’s socio-economic status (ONU,2011). Thiswasnotaffordabletomanypatients.Thus,asof2006,through the Congolese Agency for Essential and Generic Medicine (COMEG), the government of RoC established a national pro-gramme of free access to ARVs, although patients had to pay laboratorycostsformonitoringCD4+T-cellcountsandviralload measurements.Thisledtomostpatientsnotpresentingfor follow-up.Thus,accuratedataontheeffectivenessofARVsamong the PLWHAandthedegreeofdevelopmentofHIVresistancetoARVs arenotavailable.TheGlobalFundlentitssupporttoRoCin2012,

ensuringthatHIVtestingandHAARTwereprovidedfreeofcharge toPLWHAacrosspublichealthfacilitiesthroughoutthecountry. Figure2showsthegeographicaldistributionofHIVdiagnosticand treatment centres in RoC. By the end of 2014, the Centre de Traitement Ambulatoire au Congowas providing care for 6430 PLWHA,including5677(88.3%)onHAART.

Cascadeofcareandmanagementissues Adherence

AdherencebypatientstoHAARTisanimportantissueforHIV/ AIDS services across Africa (Bekker et al., 2014). HIV/AIDS treatment requires several doses of ARVs every day, thus necessitatingareliabledrugsupply.Side-effectsofARVscanalso promptPLWHAtosuspendordiscontinuetreatment(Bekkeretal., 2014).An18-monthretrospectivestudyconductedinBrazzaville of157patientsonHAARTforatleast12months,showedthatapart fromtheeffectivenessofARVsanddespiteobservedtherapyin84% cases, 10.8% took their ARVs irregularly and 5.2% stopped altogether (Dokekias et al., 2008). A study of adherence and patientcomplianceconductedinRoCin2009involvedasurveyof 214 patients (mean age 42 years and only six children) at an outpatientcareandtreatmentcentreinBrazzaville,Congo(Faure et al.,2011), inwhich itwas foundthat 92.5%of patientswere receivingfirst-lineHAARTregimensandadherenceratesachieved werebetween55%and87%.In astudythatlookedatcauses of deathinHIV-positivepatientsreceivingARVs attheFrenchRed CrossOutpatient TreatmentCentreat Pointe-Noire,RoC,one of several factors determined was non-adherence to treatment (Lucaccionietal.,2013).Furtheroperationalresearchstudiesare requiredtodefinethemainfactorsimpedingadherenceinorderto inform onappropriatemeasurestoimproveadherence,suchas publiceducationoradditionalregularfollow-up.

Optimizingandmonitoringtreatment

MonitoringofCD4+cellcountsandHIVviralloadwithinRoC HIV services is extremely limited due to non-functioning

equipment and theintermittentand scarce supply ofreagents, causingsubstantialinterruptionsinthecascadeofcare.Duetothe limitedavailabilityandchoiceofARVsinRoC,itisdifficulttotailor ARVtherapytothespecificneedsofthepatientwhentheydevelop sideeffectsorbecomeintolerant.Furthermore,sincegenotypingof HIVisolatesisnotpossibleinRoC,theoptimalchoiceofARVsis alsorestricted(Beaulièreetal.,2010).Itisevenmoredifficultto initiateasecond-orthird-linetreatmentregimeninthecaseof therapeuticfailureduetothedevelopmentofresistancetoARVs. ResistancetoARVs

The emergence and transmissionof HIV strainsresistant to ARVsisnowanimportantpublichealthprobleminRoC.Inastudy conductedin ARV-naïveHIV-infectedpatientsreportedin2012, Pircheretal.(Pircheretal.,2012a)showedgeneticdiversityof HIV-1 and thepresence of mutationsconferring antiretroviraldrug resistancein 50 drug-naïveinfected personsin RoC. The most prevalentsubtypeswereGwith10isolatesandDwith11isolates. Previous reports have shown thehigh genetic diversity in the distribution of HIV-1 subtypes in RoC. Subtypes A, G, and D predominate,butapproximately20–27%ofstrainscirculatingin thecountryarerecombinants(Ekat,2015;Churchetal.,2015a)and 6.3%ofstrainsremainunclassified.Pircheretal.concludedthatthe resistancetoARVsisthemajorcauseoftreatmentfailure(Pircher etal.,2012b).

TheadministrationofpoorqualityARVsinthecountrymayalso increasetheriskofvirusmutationsconferringresistancetodrugs (Camara et al., 2015). To prevent virological failure and the emergenceofdrugresistancemutations,therigorous pharmaco-logicalmonitoringofgenericARVsthatarenotpre-qualifiedbythe WHObutthataremarketedinAfrica,mustbeapriorityforhealth authorities(Camaraetal.,2015).

In order to reduce the risk of the development of ARV resistance, appropriate measures should be taken to educate patients,simplifydosing,andenhanceadherencemonitoring.For example,a clearand adapted case-management model for the cascade of care from HIV counselling to healthcare could be applied.Operationalresearchascertaining thereasons for poor adherence should be at the front line for improving patient adherence,andpatientswhoareatriskofbecominglostto follow-upshouldbeidentifiedproactively(Thompsonetal.,2012; Beima-Sofieetal.,2017).

Mother-to-childHIVtransmission

Astudyconductedin44selectedantenatalclinics(ANCs)in12 departmentsin RoC(fiveurbanand sevenrural)assessed 2979 pregnantwomenattendingthesefacilities(Niamaetal.,2017).The overallHIV infectionratewas estimatedtobe 3.6%.Thisstudy indicated that more investment was required to emphasize preventionstrategies toprevent mother-to-childandhorizontal transmissionofHIV.Maternalandchildmortalityandmorbidity associatedwithHIVhasbeenattributedtolateHIVscreening,the absenceordelayedinitiationofARVtherapyduringpregnancy,and inadequatetreatmentforthosewithadetectableviralloadinlate pregnancy (Vogler, 2014) . No data are available to assess the impact of this lack of optimization on maternal and child healthcare.Thenon-disclosureofthemother’sHIVstatustothe fatherofthechild,commoninAfricaincludingRoC,isassociated withlessoptimalpreventionofmother-to-childtransmission,but has no impact on mother-to-child HIV transmission (Madiba, 2013).

TherapeuticfailureamongnewlydiagnosedmothersinRoChas beenattributedtoresistantHIVstrains(Bruzzoneetal.,2015).The studyinPointe-Noireanalyzed95plasma samplesfrom HIV-1-positivetreatment-naïvepregnantwomencollectedoveraperiod

of 18 months between 2005 and 2008 . Major mutations to nucleoside reverse transcriptase inhibitors, non-nucleoside re-verse transcriptase inhibitors, and protease inhibitors were detectedin4/68(5.9%),3/68(4.4%),and2/68(2.9%)ofthepatient samples,respectively.Theextremelyhighgeneticvariabilityof virusesinRoCisanadditionalchallenge,andjustifiessystematic monitoringoftheresponsetotreatment(Bruzzoneetal.,2015); unfortunatelythisisnotthecase.

Co-trimoxazoleprophylaxis

InBrazzaville,inaccordancewithWHOHIVtreatment guide-lines,co-trimoxazoleprophylaxis(CTXp)forHIV-infectedinfants (from the ageof 4 to 6 weeks) is administeredirrespective of diseasestage,CD4cellcount,oruseofHAARTuntiltheageof14 years(Churchetal.,2015b).CTXppreventsbacterialinfectionsand PneumocystisjiroveciipneumoniainadultsandchildrenwithHIV infection(Churchetal.,2015b).CTXpalsoreducesanaemiaand improves growth in children with HIV, possibly by reducing inflammation.Studiesarerequiredtoascertainthe cost-effective-ness of CTXp in adolescents, particularly around reductions in morbidityandmortality,andimprovementsingrowth,especially forchildrenwithHIV.

ExternalfundingfortheHIV/AIDSprogrammeintheRepublicofthe Congo

Forthepastdecade,theGlobalFundhasprovidedsubstantial fundingtoRoCforHIV/AIDS,TB,andmalariaservices,amounting toanestimated51billionCFAfrancs(68305349GBP).For the years2014–2015,theGlobalFundcontributedatotalof16156313 Euros(14 195548GBP)toRoC(GlobalFund,2015),asfollows:6 233128EurostotheSecrétariatExécutifduConseilNationalede LutteContreleSIDA(ExecutiveSecretariatfortheNationalHIV/ AIDS Council), 7093150 Euros to the French Red Cross, and 2830035 Euros to the administrative and financial technical coordinationoftheMinistryofPublicHealth.Thisfundingwaspart of the second phase of theproject“Support to strengthen the nationalresponsetoHIVamongat-riskpopulationsintheCongo”, which tacklessocio-economic factorsassociated withHIV such stigmaandmarginalization.Fortheperiod2017–2019,theGlobal Fund will contribute a total of 27912895 Euros, of which 11 539955EuroswillbeforHIV/AIDSactivities.TheInternational Monetary Fundfundingfor HIV/AIDS, malaria, and TB requires theircontributionstobematchedby20%ofthetotalbythehost country. Currently,RoC is eligibleto applyto theInternational MonetaryFundallocationsfortheyears2018–2020.Donorfunding for the HIV response in low- and middle-income countries declined by almost 13% between 2014 and 2015 (UNAIDS and TheHenryJKaiserFamilyFoundation,2016).AccesstoARVshasno doubtdramaticallyreducedmortalityandmorbidity(Grace,2016) andtransformedthelivesofPLWHA,returningthem toa near-normallifespan(Samjietal.,2013).

ARVsupplychainandqualityofdrugs

The drugsupplyand rolloutchain for free ARVs in RoChas sufferedfrommanyinterruptionsandissuesofsupply,quality,and expiry dates, and this hasdogged the management of PLWHA (Agence d’information d’Afrique Centrale, 2013). Previously COMEGwasresponsiblefortheprocurementofARVsfromforeign distributors,andthestorageanddistributionoftheseARVsatthe nationallevel.RegardingthereagentsforHIVtestingand follow-upCD4+cellcountsandHIVviralloadmeasurements,advanced paymentbylocalstructureswasacceptable,withrefundsfromthe

Ministryof Public Health.The purchaseof medicines has been fundedbyboththegovernmentofRoCandtheGlobalFund.

ARVprocurementproceduresarecomplex,particularlybecause ofthemultiplicityofdonorsinvolvedinthefieldofantiretroviral drugs, withtheprocurementprocedures beingspecific toeach donor.Theordersarenotcentralizedand thisoftenresultsina breakdown of the drug supply chain (Libaudière et al., 2006), whichisnotwellestablishedinRoC.TheGlobalFundmadetwo changestoallocationstoin 2013(Anon, 2013):2013):1)funds allocatedbytheGlobalFundcouldbeusedforthedirectpurchase ofARVs,and(2)ARVsweretobechannelledthroughlocalNGOsfor distributiontothebeneficiaries.ThehealthservicesinRoChave continuedtofacedisruptionsindrugsupplyforfirst-and second-lineARVs.Asanexample,in2015therewasanacuteshortageof Atripla,a combinationpillconsistingofefavirenz,emtricitabine, and tenofovir disoproxil fumarate. This error in supply chain disruptedtheHAARTtreatmentregimensofnumerouspatients, withapossibleimpactonthedevelopmentofHIVviralresistance. Approximately12%ofthe18000patientswhoareonARVsinRoC aretakingAtripla.Duringshortages,somepatientsonAtriplaare switched to otherARV regimens that are not optimal(Agence d’information d’Afrique Centrale, 2014).The latestdrug supply shortage was recorded in March 2017, when there were an estimated23000adults andover1500 childrenonHAART.The HIV/AIDSSustainabilityIndexandDashboard(Anon,2016)isatool usedbytheUSdonoragencyPEPFAR(President’sEmergencyPlan forAIDSRelief)todetermineacountry’ssustainabilitylandscape forHIV/AIDS.Thisshouldbeusedtomonitorfundingandmake available additional funds fromthe government to sustain the risingtrajectoryofrolloutandaccesstoantiretroviraltherapy. PrioritiesforHIV/AIDSprogrammestrengtheningintheRepublicof theCongo

Table1listsprioritiesfor thescale-upofHIV/AIDS program-maticactivitiesinRoC(modifiedandadaptedfromaWHOreport (WHO Regional office for Africa, 2006)). Observing respect for human rights, fighting stigma and discrimination, advancing equity and gender-centred approaches, and putting people (PLWHA,civil society groups, community) at thecentre of the HIVandAIDSresponseiscriticaltoitssuccess.Takingforwardan unwaveringcommitmentbythegovernmentofRoCtomassively scale up and deliver a ‘cost-free’ comprehensive package of servicesforprevention,treatment,care,andsupportforHIVand AIDS is required to get everyone diagnosed and treated.

EstablishinglinksbetweenHIVservicesacrossallhealthsectors, includingmaternalandchildhealthprogrammes,andintegrating TB and HIV care will provide a holistic approach to the managementofpatients(Linguissietal.,2017).

ThelackofdataonHIVinRoCemphasizedbythisstudymakes animportantcaseforestablishinganeffectivedatamanagement systemwithaccuratereporting,record-keeping,andreportingto the WHO, allowing for more accurate data on prevalence, incidence, and trends over time. The paucity of research publications from RoC makes the performance of operational andbasicscienceresearchapriority.Thisisrequiredtofillexisting datagapsandprovideanevidencebaseonpatientadherence,ARV resistance, tailored ARV therapy, monitoring, follow-up, and surveillance. This will require increased political and financial commitmentsfromthegovernmentofRoCandincreasedexternal donorfunding.

Acknowledgements

FN,AZandMBaremembersoftheCentralAfricaNetworkon Tuberculosis,HIV/AIDSandMalaria(CANTAM2)and PANDORA-ID-NET Consortium, which are supported by the European and DevelopingCountriesClinicalTrialsPartnership(EDCTP).AZisin receiptofanNIHRseniorinvestigatorfellowship.

Fundingsource

ThispublicationispartofthePANODRA-ID-NETandCANTAM2 grants funded by the EDCTP2 programme which is supported underHorizon2020,theEuropeanUnion’sframeworkProgramme forresearchandInnovation.

Conflictofinterest

Theauthorshavenoconflictofinteresttodeclare. References

Agence d’information d’Afrique Centrale. VIH/SIDA: la rupture de molécules d’antirétrovirauxpersiste.2013Availablefrom:http://www.adiac-congo.com/ content/vihsida-la-rupture-de-molecules-dantiretroviraux-persiste-37067. [Cited5August2017].

Agenced’informationd’AfriqueCentrale.VIH/sida:lesmédicaments antirétrovir-auxaucœurd’unenouvellepolémique.2014Availablefrom: http://www.adiac- congo.com/content/vihsida-les-medicaments-antiretroviraux-au-coeur-dune-nouvelle-polemique-8198.[Accessed1August2018].[Cited14October2016]. Table1

PrioritiesforscalingupHIV/AIDSprogrammaticactivitiesintheRepublicoftheCongoa

.

1.Observingrespectforhumanrights;overcomingstigmaanddiscrimination;advancingequityandgender-centredapproaches;puttingpeople(PLWHA,civilsociety groups,community)atthecentreoftheHIVandAIDSresponse.

2.Fosteringandensuringaccountability(political,financial,moral,andprogrammatic)ateveryleveloftheresponse.Thisincludeshonest,transparent,andaccountable useofdonorfunding.

3.TakingforwardanunwaveringcommitmentbythegovernmentofRoCtomassivelyscaleupanddelivera‘cost-free’comprehensivepackageofservicesforprevention, treatment,care,andsupportforHIVandAIDS.

4.EnsuringaregularandcontinuoussupplyofHIVdiagnostics,ARVs,andlaboratoryreagentsforCD4+T-cellcounts,HIVviralloadmeasurement,andgenotypingfor resistance.

5.EstablishinglinksbetweenHIVservicesacrossallhealthsectors,includingmaternalandchildhealthprogrammes. 6.IntegratingTBandHIVcare.

7.Increasinghumanresourcesbytrainingandempoweringallgradesofhealthcareworkers,laboratorypersonnel,andcommunitycarestaff.

8.Establishingeffectivecollaborativeregionalandpan-AfricannetworkstoacceleratepriorityresearchandtrainingonHIVlinkedwithTB,malaria,respiratorytract infections,andotherco-morbidities.

9.Establishinganeffectivedatamanagementsystemwithaccuratereporting,record-keeping,andreportingtotheWHO,allowingformoreaccuratedataonprevalence, incidence,andtrends.

10.Conductingpriorityoperational,epidemiological,translational,clinical,andbasicscienceresearchtofilldatagapsandtoinformpatientadherence,ARVresistance, tailoredARVtherapy,andsurveillance.

11.Committinglocalgovernmentalfunds,increasingdomesticresources,andweaningoffdependencyonexternaldonoraid. PLWHA,peoplelivingwithHIV/AIDS;RoC,RepublicoftheCongo;ARVs,antiretrovirals;WHO,WorldHealthOrganization.

a_Modified

TheglobalfundtofightAIDS,tuberculosisandmalaria.Auditofglobalfundgrants totheRepublicoftheCongo[Internet].OfficeoftheInspectorGeneral;2013 May p. 1–37. Report No.: GF-OIG-13-009. Available from: https://www. theglobalfund.org/media/2755/oig_gfoig13009auditcongorepublic_report_en. pdf?u=636488964500000000.

Report2016:Sustainabilityindexanddashboardsummary:democraticrepublicof the Congo. https://www.pepfar.gov/documents/organization/260727.pdf. [Accessed6August2018].

BeaulièreA,LeMauxA,TrehinC,PerezF.Accesstoantiretroviraltreatmentin developingcountries:whichfinancingstrategiesarepossible?.RevÉpidémiol SantéPublique2010;58(3)171–9French.

Beima-SofieKM,BrandtL,HamunimeN,ShepardM,UusikuJ,John-StewartGC, O'MalleyG.PediatricHIVdisclosureinterventionimprovesknowledgeand clinicaloutcomesinHIV-infectedchildreninNamibia.JAcquirImmuneDefic Syndr2017;75(1):18–26.

BekkerL-G,VenterF,CohenK,etal.ProvisionofantiretroviraltherapyinSouth Africa:thenutsandbolts.AntivirTher2014;19(Suppl3):105–16.

BruzzoneB,SaladiniF,SticchiL,MayindaMboungouFA,BarresiR,CaligiuriP,etal. PrevalenceofHIV-1subtypesanddrugresistance-associatedmutationsin HIV-1-positivetreatment-naivepregnantwomeninPointeNoire,Republicofthe Congo(Kento-MwanaProject).AIDSResHumRetroviruses2015;8(31):837–40.

CamaraS,ZucmanD,VasseM,GoudjoA,GuillardE,PeytavinG.Absencede bio-équivalenced’ungénériquedulopinavir/ritonavirnonpréqualifiéparl’OMS commercialiséenAfrique(CongoBrazzaville).BullSociétéPatholExot2015;108 (1):46–8.

ChurchJA,FitzgeraldF,WalkerAS,GibbDM,PrendergastAJ.Theexpandingroleof co-trimoxazoleindevelopingcountries.LancetInfectDis2015a;15(3):327–39.

ChurchJA,FitzgeraldF,WalkerAS,GibbDM,PrendergastAJ.Theexpandingroleof co-trimoxazoleindevelopingcountries.LancetInfectDis2015b;15(March(3)) 327–39,doi:http://dx.doi.org/10.1016/S1473-3099(14)71011-4Epub2015Jan 21.

DokekiasAE,GalibaFO,BokiloAD.EvaluationdutraitementARVchezlesadules infectésparleVIHsuivisdansleserviced’hématologieduCHUdeBrazzaville, Congo.BullSociétéPatholExot2008;101:109–12.

EkatMH.PaediatriccohortofHIV-positivechildrenfollowedbytheAmbulatory TreatmentCenterofBrazzaville.2015Catania,Italia.Availablefrom:https:// www.iasociety.org/Web/WebContent/File/CIPHER_Adolescent_Transition_-Meeting_Report_2015.pdf.[Cited13October2016].

FaureN,DiafoukaM,NzounzaP,EkatMH,MahambouND,LevasseurG,etal.Study oftreatmentadherencebypatientslivingwithHIVin2009attheoutpatient careandtreatmentcenterofBrazzaville,Congo.MedTrop(Mars)2011;71 (October(5))487–91French.

GlobalFund.Boardreport2015annualreportontheactivitiesoftheofficeofthe InspectorGeneral.GlobalFund;2015GF/B35/10—Availablefrom:http://www. theglobalfund.org/en/search/?q=annual+report+2015. [Accessed 7 October 2016].

GraceJM.Exercise therapyfor acquiredimmunedeficiency syndrome (AIDS) patients.In:SozenH,editor.Fitmed.Availablefrom:http://www.intechopen. com/books/fitness-medicine/exercise-therapy-for-acquired-immune-deficien-cy-syndrome-aids-patients.[Cited21April2017].

LNSP.Rapportdel’enquêtecomportementalecoupléeauVIHchezlesPS,HSHet Détenus.Brazzaville,Congo:LaboratoireNationaldeSantéPublique;2012Juin p.2.

LibaudièreC,SibilleB,BakalaN,Tran-MinhT,MoualaC,AdamG,etal.Drugsupply forHIVpatientsindaycarecentreinRepublicofCongo:theFrenchRedCross experience.MèdTrop(Mars)2006;66(6):598–601.

LinguissiLS,GwomLC,NkenfouCN,BatesM,PetersenE,ZumlaA,etal.Health systems in the Republic of Congo: challenges and opportunities for

implementingtuberculosisandHIVcollaborativeservice,research,andtraining activities.IntJInfectDis2017;56(March):62–7.

LucaccioniV,LoubakiP,MafouaA,SimonB,MatteiJ-F,LuchtF.Causesofdeathin HIV-positivepatientsundertreatmentindevelopingcountries:experienceof theFrenchRedCrossOutpatientTreatmentCenteratPointe-Noire,Congo.Méd SantéTrop2013;23(1):22–9.

Madiba S.HIV Disclosure to partnersand familyamong womenenrolled in preventionofmothertochildtransmissionofHIVprogram:implicationsfor infantfeedinginpoorresourcedcommunitiesinSouthAfrica.GlobJHealthSci 2013;5(4)Availablefrom: http://www.ccsenet.org/journal/index.php/gjhs/ar-ticle/view/24268.[Accessed3October2018].[Cited13October2016].

NiamaFR,VidalN,Diop-NdiayeH,NguimbiE,AhomboG,DiakabanaP,etal.HIV-1 geneticdiversityandprimarydrug resistancemutationsbeforelarge-scale accesstoantiretroviraltherapy,RepublicofCongo.BMCResNotes2017;10(July (1)):243.

ONU.Différenceenmatièredetraitements Accèslimitéauxnouveaux antiré-troviraux.ChroniqueONU2011;XLVIII(1)Availablefrom:https://unchronicle. un.org/fr/article/diff-rence-en-mati-re-de-traitements-acc-s-limit-aux-nou-veaux-antir-troviraux.

PircherM,DiafoukaM,PapuchonJ,Recordon-PinsonP,MahambouDN,AkolboutM, etal.MolecularcharacterizationofHIVtype1inBrazzaville,RepublicofCongo, andfirstdataonresistancetoantiretroviraldrugs.AIDSResHumRetroviruses 2012a;28(12):1798–802.

PircherM,DiafoukaM,PapuchonJ,Recordon-PinsonP,MahambouDN,AkolboutM, etal.MolecularcharacterizationofHIVtype1inBrazzaville,RepublicofCongo, andfirstdataonresistancetoantiretroviraldrugs.AIDSResHumRetroviruses 2012b;28(12):1798–802.

SamjiH,CesconA,HoggRS,ModurSP,AlthoffKN,BuchaczK,etal.Closingthegap: increasesinlifeexpectancyamong treatedHIV-positiveindividualsinthe UnitedStatesandCanada.PLoSOne2013;8(12)OkuliczJF,editor.

SidibéM,LouresL,SambB.TheUNAIDS90–90–90target:aclearchoiceforending AIDSandforsustainablehealthanddevelopment.JIntAIDSSoc2016;19(1) Available from: http://www.jiasociety.org/index.php/jias/article/view/21133. [Cited8May2017].

ThompsonMA,MugaveroMJ,AmicoKR,CargillVA,ChangLW,GrossR, etal. Guidelinesforimprovingentryintoandretentionincareandantiretroviral adherenceforpersonswithHIV:evidence-basedrecommendationsfroman internationalassociationofphysiciansinAIDScarepanel.AnnInternMed 2012;156(11):817.

UNAIDS,TheHenryJKaiserFamilyFoundation.FinancingtheresponsetoHIVin Low- and middle-income countries: international assistance from donor governmentsin2015.Geneva,Switzerland:UNAIDS;2016.

UNAIDS,WHO.EpidemiologicalFactSheet—onHIV/AIDSandsexuallytransmitted infections:Congo.Geneva,Switzerland:UNAIDS/WHO;2004p.14. UNAIDS.GlobalHIV&AIDSstatistics—2018factsheet.http://www.unaids.org/en/

resources/fact-sheet.[Accessed8October2018].

VoglerMA.HIVandpregnancy.CurrTreatOptionsInfectDis2014;6(2):183–95. WHORegionalofficeforAfrica.TheBrazavillecommitentonscalinguptowards

universalaccesstoHIVandAIDSprevention,treatment,careandsupportin Africaby2010.Brazzaville,RepublicofCongo,8March2006.Availablefrom:

https://afro.who.int/sites/default/files/2017-06/aids_brazzaville_commitment %20%281%29.pdf.[Accessed4October2018].

WHO.Newdirectionsinthe2015WHOARTguidelines [Internet].Vancouver, Canada:WHOPress,WorldHealthOrganization,20AvenueAppia,1211Geneva 27,Switzerland[Internet].;2015Aug.Availablefrom:http://i-base.info/htb/ 28597.