Treatment Outcomes of Adult Patients Enrolled in Mozambique’s Rapidly Expanding Antiretroviral

Therapy Program during 2004-2007

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 States2Ministry of Health, National Institute of Health, Maputo, Mozambique

3CDC, Global AIDS Program, Maputo, Mozambique

Presented by Andrew F. Auld MBChB

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]- CD4 count 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

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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 CD4 count data

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

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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

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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

Factors Associated with Time to Mortality and Attrition

Baseline CharacteristicMortality

Adjusted Hazards Ratio(95% CI)

AttritionAdjusted Hazards Ratio

(95% CI)

Sex

Female 1.0 1.0

Male 1.8 (1.3-2.6) 1.4 (1.2-1.6)

WHO Stage

Stage I/II 1.0 1.0

Stage III 1.1 (0.6-2.1) 1.2 (0.9-1.6)

Stage IV 2.7 (1.5-4.9) 1.8 (1.3-2.4)

CD4+ T-cell Count

>200 cells/µL 1.0 1.0

50-200 cells/µL 1.5 (0.8-2.8) 1.0 (0.8-1.3)

<50 cells/µL 2.0 (1.9-4.2) 1.4 (1.1-1.8)

CTX Prescription

Yes 1.0 1.0

No 0.8 (0.5-1.3) 1.4 (1.0-1.8)

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Factors Associated with Time to Mortality and Attrition

Baseline CharacteristicMortality

Adjusted Hazards Ratio(95% CI)

AttritionAdjusted Hazards Ratio

(95% CI)

Sex

Female 1.0 1.0

Male 1.8 (1.3-2.6) 1.4 (1.2-1.6)

WHO Stage

Stage I/II 1.0 1.0

Stage III 1.1 (0.6-2.1) 1.2 (0.9-1.6)

Stage IV 2.7 (1.5-4.9) 1.8 (1.3-2.4)

CD4+ T-cell Count

>200 cells/µL 1.0 1.0

50-200 cells/µL 1.5 (0.8-2.8) 1.0 (0.8-1.3)

<50 cells/µL 2.0 (1.9-4.2) 1.4 (1.1-1.8)

CTX Prescription

Yes 1.0 1.0

No 0.8 (0.5-1.3) 1.4 (1.0-1.8)

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Factors Associated with Time to Mortality and Attrition

Baseline CharacteristicMortality

Adjusted Hazards Ratio(95% CI)

AttritionAdjusted Hazards Ratio

(95% CI)

Sex

Female 1.0 1.0

Male 1.8 (1.3-2.6) 1.4 (1.2-1.6)

WHO Stage

Stage I/II 1.0 1.0

Stage III 1.1 (0.6-2.1) 1.2 (0.9-1.6)

Stage IV 2.7 (1.5-4.9) 1.8 (1.3-2.4)

CD4+ T-cell Count

>200 cells/µL 1.0 1.0

50-200 cells/µL 1.5 (0.8-2.8) 1.0 (0.8-1.3)

<50 cells/µL 2.0 (1.9-4.2) 1.4 (1.1-1.8)

CTX Prescription

Yes 1.0 1.0

No 0.8 (0.5-1.3) 1.4 (1.0-1.8)

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Factors Associated with Time to Mortality and Attrition

Baseline CharacteristicMortality

Adjusted Hazards Ratio(95% CI)

AttritionAdjusted Hazards Ratio

(95% CI)

Sex

Female 1.0 1.0

Male 1.8 (1.3-2.6) 1.4 (1.2-1.6)

WHO Stage

Stage I/II 1.0 1.0

Stage III 1.1 (0.6-2.1) 1.2 (0.9-1.6)

Stage IV 2.7 (1.5-4.9) 1.8 (1.3-2.4)

CD4+ T-cell Count

>200 cells/µL 1.0 1.0

50-200 cells/µL 1.5 (0.8-2.8) 1.0 (0.8-1.3)

<50 cells/µL 2.0 (1.9-4.2) 1.4 (1.1-1.8)

CTX Prescription

Yes 1.0 1.0

No 0.8 (0.5-1.3) 1.4 (1.0-1.8)

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Factors Associated with Time to Mortality and Attrition

Baseline CharacteristicMortality

Adjusted Hazards Ratio(95% CI)

AttritionAdjusted Hazards Ratio

(95% CI)

Sex

Female 1.0 1.0

Male 1.8 (1.3-2.6) 1.4 (1.2-1.6)

WHO Stage

Stage I/II 1.0 1.0

Stage III 1.1 (0.6-2.1) 1.2 (0.9-1.6)

Stage IV 2.7 (1.5-4.9) 1.8 (1.3-2.4)

CD4+ T-cell Count

>200 cells/µL 1.0 1.0

50-200 cells/µL 1.5 (0.8-2.8) 1.0 (0.8-1.3)

<50 cells/µL 2.0 (1.9-4.2) 1.4 (1.1-1.8)

CTX Prescription

Yes 1.0 1.0

No 0.8 (0.5-1.3) 1.4 (1.0-1.8)

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Factors Associated with Time to Mortality and Attrition

Baseline CharacteristicMortality

Adjusted Hazards Ratio(95% CI)

AttritionAdjusted Hazards Ratio

(95% CI)

Sex

Female 1.0 1.0

Male 1.8 (1.3-2.6) 1.4 (1.2-1.6)

WHO Stage

Stage I/II 1.0 1.0

Stage III 1.1 (0.6-2.1) 1.2 (0.9-1.6)

Stage IV 2.7 (1.5-4.9) 1.8 (1.3-2.4)

CD4+ T-cell Count

>200 cells/µL 1.0 1.0

50-200 cells/µL 1.5 (0.8-2.8) 1.0 (0.8-1.3)

<50 cells/µL 2.0 (1.9-4.2) 1.4 (1.1-1.8)

CTX Prescription

Yes 1.0 1.0

No 0.8 (0.5-1.3) 1.4 (1.0-1.8)

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Retention Stratified By Baseline Co-Trimoxazole Prescription

17

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Prescribed CTX

Not prescribed CTX

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

Months Receiving ART

0 6 12 18 24 30 36 42 48 54

Male 160 323 329 357 373 390 411 414 440 480

Female 188 366 384 420 439 456 471 466 479 502

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

Months Receiving ART

0 6 12 18 24 30 36 42 48 54

Male 160 323 329 357 373 390 411 414 440 480

Female 188 366 384 420 439 456 471 466 479 502

Male & Female 12-month CD4 Gain: 186 cells/µL

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

Months Receiving ART

0 6 12 18 24 30 36 42 48 54

Male 160 323 329 357 373 390 411 414 440 480

Female 188 366 384 420 439 456 471 466 479 502

Females = 196 cells/µL gained

Males = 169 cells/µL gained

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

Months Receiving ART

0 6 12 18 24 30 36 42 48 54

Male 56.5 59.3 60.3 60.5 60.3 60.3 60.4 60.6 60.2 58.6

Female 52.4 55.2 56.2 56.3 56.2 56.2 56.3 56.4 56.1 54.5

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

Months Receiving ART

0 6 12 18 24 30 36 42 48 54

Male 56.5 59.3 60.3 60.5 60.3 60.3 60.4 60.6 60.2 58.6

Female 52.4 55.2 56.2 56.3 56.2 56.2 56.3 56.4 56.1 54.5

Male & Female 12-month Weight Gain: 3.8 kg

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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.

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Discussion & Public Health Impact

• Third: Initiation of ART at advanced disease stages associated with mortality and attrition:

MOH increased CD4 count 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

Acknowledgements

• 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

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

Additional Slides

28

*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]

ART Clinic Sample

12 Large Clinics (>1,000pts)

82 Small Clinics (<1,000pts)

12

18

30

Clinics SelectedClinics Included

94 clinics included in sample frame:[42, 234 (98%) of 43,295 patients)

Total

* Note that although the sample was drawn using 2006 data, we corrected sample weights during analysis to account for additional patients enrolled during 2007.

IndicatorMeta-Analysis1

(Fox et al)Rwanda Kenya Mozambique

6-month Retention

86% 92% 86% 86%

12-month Retention

78% 86% 78% 79%

24-month Retention

75% -- -- 78%

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.