ART TREATMENT PROGRAMME 2004

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Presentation title

ART TREATMENT PROGRAMME 2004 Cabinet decision in 29 th November 2003 Initial sites were hospital based, required central review National Costing Model of HIV/AIDS Treatment 2010 Cost affordability vs. cost effectiveness CD4+ less than 350 cells/mm 3 All AIDS defining illness Expanded access to treatment in PMTCT (B) Replacement of D4T with TDF Shift to primary health care, with nurse provided treatment and pharmacy assistants

THEMBA LETHU CLINIC COHORT TREATMENT OUTCOMES 2004-2010 Median CD4+ at treatment initiation 84 vs. 114 cells/ mm 3 LTFU at 1 year is similar 8.9% vs. 12.1% (2009) overall remained below 11% Over 7 years ore 8172 person years LTFU 25% and 16% had died (MR = 3.59 per 100 person years)

LTFU AND MORTALITY RATES

Probability of viral rebound Suppression <400c/ml within 6 months Rebound two consequetive viral loads > 400c/ml; or one viral >5,000c/ml Sanne I, van Rie A, J Int AIDS Soc. 2009 Dec17;12:38

Proportion remaining on initial ART 87% switches to second-line regimen were related to virologic failure Sanne I, van Rie A, J Int AIDS Soc. 2009 Dec 17;12:38

CD4+ response Mean CD4 count gain after 6 months of treatment was 117 cells/mm 3 and the increase was greater for those with CD4 counts < 200 at baseline (122 cells/mm 3 ) than those with 600 baseline CD4 CD4 count response of 200 or more (71 cells/mm 3 ) 500 400 CD4 count 300 200 100 0 0 6 12 18 24 36 Months on HAART Overall CD4 50 50 < CD4 100 100 < CD4 200 CD4 > 200

Incident TB by baseline CD 4 count (Poisson regression model) 21.7/100py (17.5-26.7) 12.8 9.5 1.5 to 2 per 100py A van Rie, I Sanne et al Int. TB and Lung Dis. Paris 2008

Treatment initiation in TB patients! ACTG A5221 (STRIDE) Early initiation of ART in patients with tuberculosis and CD4 counts <50 cells/mm 3 reduces AIDS morbidity and mortality

Total cost and potential cost savings of the national antiretroviral treatment (ART) programme in South Africa 2010 to 2017 Gesine Meyer-Rath 1,2,3, Yogan Pillay 4, Mark Blecher 5, Alana Brennan 1,2,3, Lawrence Long 2,3, Leigh Johnson 6, Harry Moultrie 3,7, Ian Sanne 2,3, Matthew Fox 1,2,3,8, Sydney Rosen 1,2,3 1 Center for Global Health and Development, Boston University, US 2 Health Economics and Epidemiology Research Office (HE 2 RO), Wits Health Consortium, South Africa 3 Faculty of Health Sciences, University of the Witwatersrand, South Africa 4 National Department of Health, South Africa 5 National Treasury, South Africa 6 Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa 7 Enhancing Children s HIV Outcomes (ECHO), Wits Health Consortium, South Africa 8 Department of Epidemiology, Boston University School of Public Health, US

Scenarios Old South African Guidelines Eligibility Adults: CD4 <200 cells/mm 3 or WHO stage 4 Children: CD4 15% to 20% or WHO stage 3 or 4 Regimens New South African Guidelines Eligibility Regimens Adults: d4t + 3TC + EFV/NVP; AZT + ddi + LPV/r Children <3 yrs: d4t + 3TC + LPV/r ; AZT + ddi + NVP Adults: CD4 <350 cells/mm 3 for TB/HIV co-infected or pregnant pts, <200 cells/mm 3 or WHO stage 4 for all others Children: Early Paediatric Treatment Adults: TDF + 3TC + EFV/NVP for all new initiates; TDF + 3TC + LPV/r if failing d4t- or AZT-containing regimens/ AZT + 3TC + LPV/r if failing TDF-containing regimens Children <3 yrs: ABC + 3TC + LPV/r; AZT + ddi + NVP Full WHO Guidelines Eligibility Regimens Adults: CD4 <350 cells/mm 3 or WHO stage 4 for all Children: Early Paediatric Treatment As in New South African Guidelines

Additional conditions New drug purchasing system (RL/FDC): ARV drugs at prices set in reference list (modelled on CHAI/ GPRM/ SCMS prices) Fixed-dose combination where possible Task shifting (TS): ARV initiation and management by nurses under physician supervision ARV dispensing by pharmacy assistants under pharmacist supervision

Health-state transition model National ART Cost Model (NACM) 6-monthly transitions between types of care and CD4-defined health states Number of patients initiating ART from ASSA2003 model Initiation rate (coverage of newly eligible pts) 80% in pts with <200 CD4 cells/mm 3 27% in pts with 200-350 CD4 cells/mm 3 Transition probabilites and rates of mortality, loss to follow-up, and first-line treatment failure based on 2 large Johannesburg cohorts: Themba Lethu Clinic Cohort (n= 9,502) Harriet Shezi Children s Clinic (n= 3,748) Transition probabilities and rates depend on CD4 cell count/ percentage and, for adult firstline treatment, also on time on treatment Model is evaluated for 2010/11 to 2016/17, with a run-in between 2003/4 and 2009/10

Regimen distribution (Adults) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2010/11 2016/17 2010/11 2016/17 2010/11 2016/17 Old Guidelines New Guidelines Full WHO Guidelines AZT+3TC+LPV/r 0% 0% 0.1% 4% 0.1% 4% TDF+3TC+LPV/r 0% 0% 1% 2% 1% 2% AZT+ddI+LPV/r 3% 6% 2% 0.4% 2% 0.4% AZT+3TC+EFV/ NVP 0% 1% 0.3% 8% 0.3% 8% TDF+3TC+EFV/ NVP 4% 9% 36% 75% 37% 72% d4t+3tc+efv/ NVP 93% 84% 61% 11% 60% 13%

Results: Regimen distribution (Children) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2010/11 2016/17 2010/11 2016/17 2010/11 2016/17 Old guidelines New guidelines Full WHO guidelines AZT + ddi + LPV/r 1.8% 2.4% 1.7% 1.4% 1.7% 1.4% AZT + ddi + EFV 0.8% 1.1% 0.7% 2.6% 0.7% 2.6% ABC + 3TC + EFV 0.0% 0.0% 33.0% 9.4% 33.0% 9.4% d4t + 3TC + EFV 51.4% 46.2% 14.1% 1.2% 14.1% 1.2% ABC + 3TC + LPV/r 0.0% 0.0% 24.0% 71.7% 24.0% 71.7% d4t + 3TC + LPV/r 45.8% 50.1% 26.4% 13.4% 26.4% 13.4%

Results: Total number of patients 4,000,000 Number of pa4ents over 4me 3,500,000 3,000,000 2,500,000 2,000,000 1,500,000 1,000,000 + 13% + 17% + 193% Old Guidelines New Guidelines Full WHO Guidelines 500,000 0 2009 2010 2011 2012 2013 2014 2015 2016 à Growth in number of patients on ART over time as a result of prevalence is higher than growth in patients as a result of increase in eligibility

Regimen distribution (Adults) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2010/11 2016/17 2010/11 2016/17 2010/11 2016/17 Old Guidelines New Guidelines Full WHO Guidelines AZT+3TC+LPV/r 0% 0% 0.1% 4% 0.1% 4% TDF+3TC+LPV/r 0% 0% 1% 2% 1% 2% AZT+ddI+LPV/r 3% 6% 2% 0.4% 2% 0.4% AZT+3TC+EFV/ NVP 0% 1% 0.3% 8% 0.3% 8% TDF+3TC+EFV/ NVP 4% 9% 36% 75% 37% 72% d4t+3tc+efv/ NVP 93% 84% 61% 11% 60% 13%

Results: Regimen distribution (Children) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2010/11 2016/17 2010/11 2016/17 2010/11 2016/17 Old guidelines New guidelines Full WHO guidelines AZT + ddi + LPV/r 1.8% 2.4% 1.7% 1.4% 1.7% 1.4% AZT + ddi + EFV 0.8% 1.1% 0.7% 2.6% 0.7% 2.6% ABC + 3TC + EFV 0.0% 0.0% 33.0% 9.4% 33.0% 9.4% d4t + 3TC + EFV 51.4% 46.2% 14.1% 1.2% 14.1% 1.2% ABC + 3TC + LPV/r 0.0% 0.0% 24.0% 71.7% 24.0% 71.7% d4t + 3TC + LPV/r 45.8% 50.1% 26.4% 13.4% 26.4% 13.4%

Scenario Results: Total cost [million 2009 ZAR] Full cost (Staffing and drug cost as current) Reduced cost (With task-shifting and reference list for drug prices) 2010/11 2016/17 Total 2010/11 2016/17 Total Change on Full cost Old Guidelines 7,729 19,053 94,647 4,900 12,090 59,961-33% New Guidelines 8,317 22,869 110,152 5,190 14,865 70,489-35% Change on Old GL (Full cost) 8% 20% 17% -29% -22% -25% - Full WHO Guidelines 9,731 25,209 124,925 6,044 16,323 79,565-33% Change on Old GL (Full cost) 27% 33% 32% -11% -14% -16% - à The total cost of the programme increases by 17% and 32%, resp., for the New Guidelines and WHO Guidelines scenarios, as a result of both higher numbers of patients and higher drug cost for TDF-containing regimens.

Progress of the National Treatment Program 2.7 Million patients initiated on treatment at over 1400 facilities >95% HIV testing and treatment offered in pregnancy; >90% of TB patients are offered HIV testing, the early initiation of treatment is only variably implemented PMTCT rates below 3.8% at 6 weeks Mortality rates have declined from 2004-2012 (540,000 to 370,000) Drug pricing is low but companies are not investing in the chemical production facilities Key population remain a focus

Clinic reported HIV drug stock-out

HIVDR patters following first-line ART M184V in 64% of patients failing Several TAMs in the population K65R at 5% Wallis C, Mellors J, Venter F, Sanne I and Stevens W - J AIDS. 2010 Apr 1;53(4):480-4

HIVDR patters following first-line ART K103N V106M Y181C G190A Wallis C, Mellors J, Venter F, Sanne I and Stevens W - J AIDS. 2010 Apr 1;53(4):480-4

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