1. Early survival and clinic retention among high risk HIV-infected patients initiating cART in a pilot Express Care system compared to Routine Care in Western Kenya P. Braitstein 1-4, J. Hogan 4,5, A. Siika 1,2,4, R. Kosgei 4, E. Sang 4, J. Sidle 1,2,4, K. Wools-Kaloustian 1,2,4, C. Yiannoutsos 1,2,4, W. Tierney 1-4, J. Mamlin 1,2,4, S. Kimaiyo 1,4 1. Moi University School of Medicine, Eldoret Kenya; 2. Indiana University School of Medicine, Indianapolis, USA; 3. Regenstrief Institute, Indianapolis, USA; 4. USAID- AMPATH Partnership, Eldoret, Kenya; 5. Brown University, Rhode Island, USA

2. Background  Roughly 3 million people receiving cART 31% of individuals in need Health systems and budgets stretched  Many people still presenting for care in advanced stages of disease Poorer prognosis Early months highest risk

3. Relative hazard of mortality: ART-LINC vs. ART-CC  unadjusted HR  adjusted HR (adjusted for cohort, age, sex, baseline CD4, ART-regimen, disease stage) ART-LINC Collaboration, The Lancet 367(9513): 817- 824. 2006

4. Setting: USAID-AMPATH Partnership Academic Model for the Prevention And Treatment of HIV/AIDS: launched in 2001 Moi University School of Medicine, Moi Teaching & Referral Hospital, and Indiana University USAID (PEPFAR) support in 2004 Since 2001: > 70,000 HIV-infected men, women, and children 18 urban and rural clinics throughout Western Kenya Currently: > 55,000 active patients Supported in clinical care and research by a consortium of North American universities known as the ASANTE Consortium

5. High Risk Express Care  Pilot project initiated in March 2007 4 high volume clinics  Two aims: Clinical: To reduce mortality in HIV-infected adults with CD4 counts ≤100 cells/mm 3 initiating cART. Programmatic: To increase clinic capacity without increasing costs.  Rolled out to all 18 by June 2008  More in-depth details on the program:  Kosgei et al. Wednesday 11:05 am (WEAX0102)

6. Routine Care (RC) for patients initiating cART Clinical Officer sees patient at every visit and prescribes cART Patient is scheduled to return monthly (unless clinical indications warrant otherwise)

7. High Risk Express Care (EC) Clinical Officer (CO) sees patient at initial visit CO prescribes cART –Refers patient to EC upon cART initiation –CO sees the patient every 4 weeks thereafter –In between: Nurse either sees patient in clinic or talks to them by phone every intervening week for 3 months Tests vital signs and conducts a rapid symptom assessment Any clinical indication warrants immediate referral to Clinical Officer

8. Primary Research Question Does being in the High Risk Express Care program reduce early mortality and losses to follow-up for patients initiating cART with a CD4 count ≤100 cells/mm 3 ?

9. Study Design Retrospective observational study Patient Inclusion:  Initiating cART  CD4 count of ≤100 cells/mm 3  Aged 14 years and over Primary outcomes:  All-cause mortality  Lost to follow-up Defined as being absent from the clinic for at least 3 months, with no indication that patient had died

10. Analysis Parametric and non-parametric descriptive statistics Comparing being in Express Care vs. Routine Care Kaplan Meier methods used to calculate time to event and probability of remaining alive and in care Survival curves were compared using Wilcoxon Log Rank test. Cox Proportional Hazards modelling Adjusted Hazard Ratios (AHR) 95% confidence intervals (CI) Variables entered into final model if –statistically significant at an alpha of 0.05 –potential confounders

11. VariableExpress Care N=378 Routine Care N=2223 p-value Male39%40%0.810 Median age36.937.50.418 Median CD4 at cART47440.620 WHO Stage III/IV at cART initiation 66%70%0.188 On TB T x at cART31%35%0.130 Attending an urban clinic68%46%<0.001 Use of Septrin at cART98%90%<0.001 Median visits per month2.11.4<0.001 Patient Characteristics

12. Results Express CareRoutine CareTotal N events (total) 32316348 N deaths14142156 N LTFU18174192 Person- Months of Follow-up Median 5.3 Median 4.211,464

13. Probability of remaining alive 0.00 0.25 0.50 0.75 1.00 0100200300 analysis time RoutineExpress Log Rank p=0.009

14. Probability of remaining alive and in care 0.00 0.25 0.50 0.75 1.00 0100200300 analysis time RoutineExpress Log Rank p<0.001

15. Sub-Analysis Concern over selection bias Clinics Patients into EC Restricted to clinics who initiated EC Patients eligible for sub-analysis if: They initiated cART after EC was initiated in the clinic They were eligible for EC (i.e. CD4<100)

16. Sub-Analysis Express CareRoutine CareTotal N336379715 Total N Events315788 Months of Follow-up Median 5.3 Median 3.83598 N deaths123042 N LTFU192748

17. VariableExpress CareRoutine Carep-value Male40%36%0.218 Median age36.136.70.554 Median CD4 at cART4647.50.833 WHO Stage III/IV at cART initiation 64%69%0.235 On TB T x at cART31%41%0.130 Attending an urban clinic66%53%<0.001 Use of Septrin at cART98%91%<0.001 Median visits per month2.21.5<0.001 Patient Characteristics (N=715)

18. Probability of Remaining Alive 0.00 0.25 0.50 0.75 1.00 0100200300400 analysis time RoutineExpress Log Rank p=0.003

19. Probability of Remaining Alive and In Care 0.00 0.25 0.50 0.75 1.00 0100200300400 analysis time RoutineExpress Log Rank p=0.030

20. All patients who initiated cART with CD4<100 Death Alone N events: 156 Death & LTFU N events: 348 In Express Care 0.54 (0.31-0.94)0.58 (0.40-0.84) Only patients initiating cART with CD4<100 in a clinic with EC Death N events: 42 Death & LTFU N events: 90 In Express Care 0.55 (0.25-1.20)0.80 (0.47-1.35) Adjusted* Hazard Ratios (95% CI) *adjusted for sex, age, CD4 at cART initiation, treatment for tuberculosis at cART initiation, clinic, use of Septrin or Dapsone at cART initiation, and WHO Clinical Stage at cART initiation

21. Limitations Observational data:  Clinical protocols vs. their enactment Referral to EC Adherence to other protocols, e.g. Septrin prophylaxis  Incomplete ascertainment of outcomes  Telephone encounters not documented  Difficult to assess major operational difference (frequency of clinical visits)

22. Conclusions High Risk Express Care program: May improve early survival and clinic retention for high risk HIV-infected individuals initiating cART. Not known if because: Early identification and management of symptoms (whether from immune reconstitution syndrome or other pathophysiologic causes) Improved adherence to cART Clinicians and nurses who refer to and/or work in EC may be better trained in and/or more attentive to clinical protocols and patient care

23. Acknowledgements Indiana University School of Medicine Moi University School of Medicine Moi Teaching and Referral Hospital This research was supported in part by a grant to the USAID-AMPATH Partnership from the United States Agency for International Development as part of the President’s Emergency Plan for AIDS Relief (PEPFAR). Moi Teaching and Referral Hospital