A.F. Auld MBChB 1 , F. Mbofana MD 2 , R. W. Shiraishi PhD 1 , M. Sanchez DrSc 3 ,

1. Treatment Outcomes of Adult Patients Enrolled in Mozambique’s Rapidly Expanding Antiretroviral Therapy Program during 2004-2007 Presented by Andrew F. Auld MBChB A.F. Auld MBChB1, F. Mbofana MD2, R. W. Shiraishi PhD1, M. Sanchez DrSc3, C. Alfredo MD, MPH3, L.J. Nelson MD, MSc, MPH3, T. Ellerbrock MD1 1CDC, Global AIDS Program, Atlanta, United States 2Ministry of Health, National Institute of Health, Maputo, Mozambique 3CDC, Global AIDS Program, Maputo, Mozambique

2. Mozambique • Population of 21 million • Adult HIV prevalence 14%1 • 1.6 million people living with HIV/AIDS1 • 473,000 need antiretroviral therapy (ART)1 • 3 physicians per 100,000 population2 (1) MOH Report. Impacto demografico do HIV/SIDA em Mozambique, 2009. (2) WHO. World Health Report, 2006.

3. Mozambique’s ART Program • During 2004-2007 numbers of adult ART enrollees increased 16-fold from <5,000 to 79,500 • Eligibility for ART: • defined by WHO clinical staging and CD4 count criteria: • Clinical stage IV • Clinical stage III with CD4< 350 • Clinical stage I or II with CD4< 200 • First-line regimen: stavudine (D4T), lamivudine (3TC), and nevirapine (NVP) or efavirenz (EFV) • All patients eligible for ART also eligible for Co-trimoxazole (CTX) • Baseline and 6-monthly CD4 counts and weight measurements were recommended

4. Study Objectives • Treatment outcomes of the ~75,000 adult patients starting ART during 2004-2007 have not yet been reported • In 2008, we initiated a study to: • Describe clinical & demographic characteristics at ART initiation • Estimate treatment outcomes: • Mortality rates • Attrition rates [death, loss to follow-up (LTFU), stopping ART] • CD4count gains • Weight gains • Investigate baseline characteristics associated with outcomes

5. Methods • Design: • Retrospective cohort • Target population: • All adults >14 years old at ART initiation enrolled during 2004-2007 • Sample Size: • Aimed for + 3% precision around 6-month attrition proportion • 2,600 medical records sufficient • Sampling in two stages: • Site selection: • Of 94 sites with >50 adult ART enrollees, 30 selected using probability-proportional-to-size sampling • Patient record selection: • Simple random sampling used to select 2,600 medical records

6. Methods • Abstractors completed standard questionnaires • Data double entered using CSPro software • Data analysis using SAS 9.2, STATA 11, and SUDAAN software • Survey design was controlled for and data were weighted • Analysis methods: • Multiple imputation to impute missing baseline data • Kaplan-Meier curves to examine survival and attrition • Cox proportional hazards regression models • SAS PROC MIXED used to fit polynomial growth curve models to weight and CD4count data

7. Results

8. Baseline Characteristics • Medical records of 2,596 adult ART patients were abstracted • Demographics at ART initiation: • Median age was 34 [Inter Quartile Range (IQR), 28-42] • 62% were female • 53% were married or in a civil union • Clinical characteristics at ART initiation: • 63% were WHO stage III/IV • Median CD4 count was 153/µL (IQR, 74-231/µL) • 16% had counts <50/μL • 66% counts <200/μL • Median BMI was 20.5 (IQR, 18.1-22.9) • 28% had a BMI <18.5

9. Treatment Outcomes • Treatment: • D4T, 3TC, and NVP or EFV prescribed to 88% of patients • 31% were prescribed CTX • Median duration of follow-up was 1.3 years (IQR, 0.7-2.2) • Of 2,596 patients sampled: • 164 died, • 564 were LTFU, • and 10 stopped ART, during 4,001 patient-years of follow-up

10. Treatment Outcomes • Attrition at 12 months was 21%: • 15% were LTFU • 5% dead • 1% stopped ART • 56% of deaths and 41% of LTFU occurred within 90 days • Mortality rate: • Mortality rate <90 days: 12.9 deaths/100 person-years • Mortality rate >90 days: 1.8 deaths/100 person-years • Attrition rate: • Attrition rate <90 days: 57.2 attritions/100 person-years • Attrition rate >90 days: 13.2 attritions/100 person-years

11. Factors Associated with Time to Mortality and Attrition

12. Factors Associated with Time to Mortality and Attrition

13. Factors Associated with Time to Mortality and Attrition

14. Factors Associated with Time to Mortality and Attrition

15. Factors Associated with Time to Mortality and Attrition

16. Factors Associated with Time to Mortality and Attrition

17. Retention Stratified By Baseline Co-Trimoxazole Prescription

18. Modeled Changes in CD4 Count over Time for Surviving Patients Initiating ART During 2004-2007

19. Modeled Changes in CD4 Count over Time for Surviving Patients Initiating ART During 2004-2007 Male & Female 12-month CD4 Gain: 186 cells/µL

20. Modeled Changes in CD4 Count over Time for Surviving Patients Initiating ART During 2004-2007 Females = 196 cells/µL gained Males = 169 cells/µL gained

21. Modeled Changes in Weight over Time for Surviving Patients Initiating ART During 2004-2007

22. Modeled Changes in Weight over Time for Surviving Patients Initiating ART During 2004-2007 Male & Female 12-month Weight Gain: 3.8 kg

23. Discussion & Public Health Impact • Findings limited by retrospective design and missing data in records • Four findings useful for MOH and implementing partners • First: ART program outcomes are comparable with those reported from other resource-constrained settings: • E.g. 1-year attrition proportion • In Mozambique: 21% • Mean for African ART programs: 22%3 • Second: Female treatment outcomes were superior • MOH is considering implementing and evaluating male-specific interventions to improve outcomes (3) Fox MP et al. Tropical Medicine and International Health. 2010. 15(s1): 1-15.

24. Discussion & Public Health Impact • Third: Initiation of ART at advanced disease stages associated with mortality and attrition: • MOH increased CD4count threshold for ART initiation in late 2009 from 200 to 250/µL • Fourth: CTX prescription at baseline, documented for about one third of patients, was associated with better outcomes: • USG and MOH have planned urgent CTX scale-up in 2010

25. Co-authors Dr. Francisco Mbofana Dr. Ray Shiraishi Dr. Mauro Sanchez Dr. Charity Alfredo Dr. Lisa Nelson Dr. Tedd Ellerbrock Collaborators Dr. Sarah Gimbel-Sherr Dr. Alice Magaia Dr. Jon Kaplan Dr. Barb Marston Dr. Elliot Raizes Dr. Stefan Wiktor Dr. Bill Levine Acknowledgements

26. Thank You! Disclaimer: The findings of this presentation are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention

27. Additional Slides

28. ART Clinic Sample *By December ‘06 - 152 ART Clinics - 43,295 adults (>14) Exclude if < 50 patients at ART clinic: - 58 clinics excluded [1,061 (2%) of 43,295 patients] 94 clinics included in sample frame: [42, 234 (98%) of 43,295 patients) Clinics Included Clinics Selected 12 Large Clinics (>1,000pts) 12 82 Small Clinics (<1,000pts) 18 Total 30 *Note that although the sample was drawn using 2006 data, we corrected sample weights during analysis to account for additional patients enrolled during 2007.

29. Retention of Randomly Selected Adults Starting ART in 3 Countries during 2004-2007 Compared with Results from a Met-analysis by Fox et al Fox MP and Rosen S. Patient Retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic review. Tropical Medicine and International Health. 2010. 15(s1): 1-15.