Reduced treatment delays for drug-resistant TB/HIV co-infected patients with decentralised care and rapid Xpert MTB/Rif test in Khayelitsha, South Africa Helen Cox, Jennifer Hughes, Sizulu Moyo, Johnny Daniels, Vivian Cox, Mark Nicol, Gilles van Cutsem and Virginia Azevedo

The global TB situation Estimated incidence, 2012 Estimated number of deaths, 2012 940,000* (0.8–1.1 million) 8.6 million (8.3–9.0 million) 450,000 (300,000–600,000) All forms of TB Multidrug-resistant TB HIV-associated TB 1.1 million (1.0–1.2 million) 320,000 (300,000–340,000) Source: WHO Global Tuberculosis Report 2013 Despite some improvements, TB still exerts an enormous global toll and in most high HIV and TB prevalence settings, TB is the leading cause of death among people living with HIV 170,000 (100,000–240,000) * Excluding deaths attributed to HIV/TB

Access to DR-TB treatment Target Projected Actual Poor progress in scaling up DR-TB treatment globally ~450,000 incident cases annually <20% of estimated cases receive treatment WHO TB Report 2013

South Africa 18% Adult HIV prevalence 1,000/100,000/year TB incidence 63% of TB patients are HIV infected TB is the leading cause of death (54,000 deaths in 2011) ~14,000 cases of rifampicin-resistant TB (DR-TB) diagnosed in 2012

The DR-TB treatment gap in South Africa Source: NDOH data 2013

Delays to DR-TB treatment initiation (South Africa) Setting Diagnostic method Median time to DR-TB treatment initiation Northern Cape, 2009-10 Line probe assay 62 days Western Cape, 2007-11 55 days Western Cape Hospital, 2007 Culture and DST 44 days (hospitalised patients) KwaZulu Natal, 2001-2008 84 days KwaZulu Natal, 2008-09 72 days References: Hanrahan et al PLoS ONE 2012; Jacobson et al Clin Inf Dis 2011; Bamford et al SAMJ 2010; Heller et al IJTBLD 2010; Loveday et al IJTBLD 2012

Xpert MTB/Rif for TB and DR-TB diagnosis rolled out across South Africa Xpert for all presumptive TB To date, 3.5 million specimens have been tested GeneXpert instrument placement across South Africa, May 2014 Time to result = 1.5 hours

Benefits of rapid treatment initiation Rapid mortality (<1 month) among diagnosed patients in Tugela Ferry, KZN 90% HIV infected And of course, reduced community transmission 98% HIV infected Gandhi et al, Am J Resp Crit Care Med 2010

Aim To assess the impact of Xpert for RR-TB diagnosis on treatment initiation in the context of decentralised DR-TB treatment in Khayelitsha, Cape Town

Khayelitsha Population ~ 400,000 Antenatal HIV prevalence 37% (26,000 pts on ART) ~ 5,100 TB cases registered each year (75% HIV infected) DOTS treatment success ~ 80% Approximately 200 rifampicin-resistant cases/year (75% HIV-infected) 10 health facilities providing HIV/TB/DR-TB diagnosis and treatment

Khayelitsha decentralised model Hospital admission only if clinically indicated PHC doctors initiate treatment and review monthly in local clinics Daily DOT and nurse management in clinics Integration with ART provision Specialist paediatric outreach support Local audiometry screening service Individual counselling, home visits, support groups, social worker support Recording and reporting at sub-district level The decentralised model of care is integrated into the existing TB/HIV treatment programme at primary health care level. Patients are only admitted to hospital if clinically necessary; the majority of patients are diagnosed, initiated on treatment and reviewed regularly in their local clinics by PHC doctors. Patients attend clinic for daily DOT by the nurses, who also monitor and manage common side effects, with referral to the doctor as necessary. All HIV positive patients with DR-TB are routinely initiated on HAART in the same clinic by the PHC doctors. Paediatric cases or contacts are reviewed monthly by a visiting paediatric specialist, and all DR-TB patients have access to a local hearing screening service provided by MSF. Patients are further supported throughout their treatment with individual counselling and home visits, weekly support groups and psycho-social assistance.

Implementation of interventions by year 2003-2006   2007-2008 2009 2010 2011 2012 2013 DST Method Culture (phenotypic) Mix of Culture (phenotypic) and LPA LPA Xpert RR-TB model of care Centralized Limited decentralization Improved programme implementation Full decentralization

Cases diagnosed and treated by year   2003-06 2007-08 2009 2010 2011 2012 2013 No. diagnosed Not available 218 212 195 219 210 No. treated 158 257 182 173 191 197 % treated 83.5 85.8 88.7 87.2 93.8 Consistently high % of patients initiate treatment

Time to DR-TB treatment LPA impact Decentralisation impact

HIV and time to RR-TB treatment

HIV and % initiating RR-TB treatment Xpert Across 2012-13, significant difference in treatment initiation between HIV negative and HIV infected, p<0.0001

Time to treatment (2011-12, Xpert) ● deaths, censored P=0.134, Not significant

Conclusions Decentralisation of DR-TB treatment reduced time to treatment from 2.5 months to <1 month Xpert reduced time to treatment to a median of 7 days, with more than 90% of HIV infected RR-TB cases starting treatment Rapid diagnosis is likely to reduce early mortality among HIV infected, although earlier presentation still required With well functioning systems, new diagnostic tests can translate into reduced time to treatment

Acknowledgments City of Cape Town Health Department Western Cape Province National Health Laboratory Service Staff in Khayelitsha clinics Médecins sans Frontières staff DR-TB patients in Khayelitsha