Models of Care for People with Drug-Resistant TB: Advancements in South Africa Dr. Norbert Ndjeka MD, DHSM (Wits), Dip HIV Man (SA), MMed (Fam Med) (MED) Director, Drug-Resistant TB, TB & HIV National TB Prevalence Survey

OUTLINE Background and TB burden in South Africa Models of care The use of bedaquiline in South Africa Concluding remarks

BACKGROUND

HEALTH SERVICES IN SOUTH AFRICA Population: 50, 586 757 Provinces – 9 Districts - 53 Sub districts - 253 Health facilities – 4790 MDR-TB beds: 2,500 DR-TB treatment sites: 298 GP 22.4% LP 11% NW 6.4% MP 7.2% FS 5.5% KZN 21.4% NC 2.2% EC 13.5% WC 10.5% 11/26/2018 Dr. Norbert Ndjeka

GXP sites Culture / LPA sites NTBRL

TB Burden in RSA TB patients initiated on treatment decreasing: 406,082 to 332,170 (2009 and 2013) Treatment success rate: 80,9 % for 2012 cohort MDR-TB numbers initiated on treatment doubled between 2010 and 2013 (5,313 to 10,719) MDR-TB treatment success rate of 49 % (2012 cohort > 8,000) XDR-TB treatment success rate is 20 %

Challenges Waiting time before admission : 1 - 3 month (s) Long distance of transportation for admission and follow up Negative impact on social and economic status Risk of transmission in hospital Poor outcome of DR-TB cases 11/26/2018 Dr. Norbert Ndjeka

Benefits of Decentralization Reduce transmission of DR-TB by initiating treatment sooner Make more beds available Improved adherence to medication Improved cost effectiveness Accommodate patient roles and responsibilities 11/26/2018 Dr. Norbert Ndjeka

Historical background July ‘09 First workshop on community-based MDR-TB at Kopanong Hotel, Johannesburg, facilitators Drs. Jaramillo & Nkhoma Oct ‘09 Workshop on best practices and community MDR-TB. Facilitators: Drs. Bayona & Alcantra May ‘10 Discussion and adoption of the decentralised MDR-TB approach by TB Managers during quarterly meeting Jun ‘10 Circulated draft policy framework on decentralized management of MDR-TB Nov ‘10 National MDR-TB workshop to plan implementation May ’11 Final draft discussed by Technical Committee at National Health Council meeting 26 Aug ’11 Approval Oct ‘11 Printing 11/26/2018 Dr. Norbert Ndjeka

Levels for the Decentralized Management of DR-TB 11/26/2018 Dr. Norbert Ndjeka

Essential elements for Decentralization Decentralized site Access to lab services Access to DR TB Drugs Access to Audiometry Health care professional initiating DR TB mx

MODELS OF CARE

Provinces requested to Call meetings of all stakeholders to introduce the policy framework Identify health facilities for scale up of MDR-TB services (plan, decentralized units, satellite units, PHC and injection teams) Conduct facility readiness assessment of all proposed/identified facilities Train all potential Care providers Monitor & Evaluate decentralization of MDR-TB activities 11/26/2018 Dr. Norbert Ndjeka

Criteria for models of care In patient care Patient is not clinically well Co-morbidities that presents with secondary complications Serious adverse reactions Outreach Model A clinician based at another unit provides outreach services to areas where there are no initiators The clinician will travel to the various facilities to initiate patients and also provide follow up The above can be done as an ambulatory service or admission to a satellite facility Ambulatory Model Patients are initiated at Primary health care level No admission is required The patient managed according to this model is clinically stable

MDR-TB Treatment Strategies

Initiatives to support Decentralization

Initiatives to support Decentralization Park homes are being utilized to bridge the infrastructure challenges. They are utilized as the OPD facilities for DR TB patients. It is also an option for admission and serving as a ward where infrastructure is inadequate

Summary of Decentralization: before 2011 Province Central site Decentralized site(Initiating) Satellite Injection teams NIMDR SITES Eastern Cape 1 Free State Gauteng KZN 4 - Limpopo Mpumalanga Northern Cape North West Western Cape 2 South Africa 9 8

Summary of Decentralization: progress Province Central site Decentralized site(Initiating) Satellite Injection teams NIMDR SITES Reporting units Districts without decentralized units Eastern Cape 1 14 10 4 Free State 15 5 3 Gauteng 46 2 KZN 11 80 8 Limpopo 9 19 Mpumalanga Northern Cape 13 John Toale Ambulatory care North West Western Cape 185 261 2 Districts have an outreach Model South Africa 298 272 150 37

MDR-TB treatment outcomes (2012 cohort KZN) All Cases HIV Positive On ART Cured 1277 949 847 Treatment Completed 477 348 302 Failed 98 75 72 Defaulted 566 406 326 Died 440 362 327 Transferred Out 46 32 23 Not evaluated 83 60 50 Still on treatment 21 19 Total 3010 2253 1966 Treatment Success Rate 58 %

XDR-TB treatment outcomes (2012 cohort KZN) All Cases HIV Positive On ART Cured 32 25 Treatment Completed 20 17 14 Failed 22 15 Defaulted 30 23 21 Died 40 28 26 Transferred Out Not evaluated 5 4 Still on treatment Total 154 117 108 Treatment Success Rate 34 % 36 %

National TB Prevalence Survey

THE USE OF BEDAQUILINE IN SOUTH AFRICA

Methods Pre-XDR and XDR TB patients at five approved sites across South Africa were selected by pre-defined criteria

Provides energy (ATP) from a trans-membrane proton gradient Mechanism of Action In strains resistant to bedaquiline, mutations were identified in the gene coding for ATP synthase Provides energy (ATP) from a trans-membrane proton gradient Adapted from Science 2005, 307, 214

Culture negative at start n=15 Culture negative at start n=6 Enrolled, started on BDQ and included in the analysis n=91 33 XDR-TB 41 pre XDR (FLQ) 17 pre XDR (injectable) >24 weeks since treatment start n=60 Completed 24 weeks BDQ n=58 Died n=2 Transferred out n=1 Defaulted n=1 On continuation treatment n=54 Culture negative at start n=15 Culture converted n=33 Still culture positive n=6 Did not complete BDQ n=2 Died n=1 <25 weeks since treatment start n=31 Still on treatment n=31 Culture negative at start n=6 Culture converted n=10 Culture pending n=15 Figure 1. Interim outcomes for XDR and pre XDR TB patients enrolled in National Bedaquiline Clinical Access Programme in South Africa 60 patients started BDQ over 6 months ago and 58 patients completed 6 months of treatment (one died and one defaulted) 52 were culture negative at 6 months giving a culture negative rate at 6 months of 86.6% 31 have had less than 6 months of treatment of those 16 have had at least two negative cultures separated by 30 days. BDQ: bedaquiline; XDR TB: extensively drug resistant TB; FLQ: fluoroquinolone National TB Prevalence Survey

Culture conversion by resistance pattern Although the numbers are small, the rate of culture conversion is not affected by resistance patterns. National TB Prevalence Survey

Culture conversion by HIV status status All patients who were HIV infected were on ART at the time of starting BDQ. There is not difference in the culture conversion rate by HIV status. National TB Prevalence Survey

Results – median QTcF

Results – QTcF by ART regimen Although there are small numbers, there increase in QTcF does not appear to be greater in patients who are given LPV/ vs NVP. Also of note that that patient with a QTcF at two and three months was no NVP and not LPV/r National TB Prevalence Survey

Results – QTcF by clofazimine exposure National TB Prevalence Survey

CONCLUDING REMARKS

Conclusion The programme has allowed access to better treatment hence the good interim outcomes for (pre-)XDR patients with otherwise limited options and poor prognosis Bedaquiline is now registered in South Africa and will be used next year within the TB programme under strict control

Conclusion (2) Decentralized management of MDR-TB increases access to care + NIMDR It reduces time to MDR-TB treatment initiation which may reduce community transmission of MDR-TB Decentralized management of MDR-TB produces outcomes similar to hospitalization generally; and sometimes even better outcome than hospitalization 11/26/2018 Dr. Norbert Ndjeka

Thank you 11/26/2018 Dr. Norbert Ndjeka