Documents
Resources
Learning Center
Upload
Plans & pricing Sign in
Sign Out
Get this document free

Slide 1 - Kheth'Impilo

VIEWS: 6 PAGES: 27

									    Good Three-year Outcomes of
Antiretroviral Therapy at Multiple NGO-
assisted facilities in Four Provinces in
               South Africa
   Geoffrey Fatti, Ashraf Grimwood & Peter Bock


          Absolute Return for Kids South Africa
      Background


•ARK SA: NPO established in November 2003

Mission: To reduce HIV/AIDS related orphan
hood by improving ART access to parents and
carers at a primary healthcare level in a
sustainable manner, in partnership with
government
        Background
        Overall program outputs: Nov 08
111 ARK-supported sites in four provinces in SA:
Western Cape, Eastern Cape, Kwazulu-Natal,
Mpumalanga


61 995 ARV patients enrolled at ARK-supported sites
~ 10% of patients enrolled in the public sector
The ARK model
        Aim and Objectives
Aim: Evaluate the ARK ART clinical services program
Objectives:
1.   a - Report ART program outcomes at all ARK-
     supported sites in SA.
     b - Identify baseline patient factors associated with
     poor outcome.
2.     Compare outcomes with other programs
     •   -Sub-Saharan Africa
     • -developed countries.

3.   TB treatment outcomes: Compare ARK-assisted
     sites vs. non ARK-assisted TB treatment facilities.
            METHODS
             Objective 1: ART program outcomes
      Sample population:
    • All ART-naïve adults ( ≥16) starting ART at facilities supported by
      ARK between November 2003 and December 2007

      Outcome measures:
    • Death, loss to follow-up (LTFU) & virological suppression (VLS)

     Definitions:
• Time measured from date of ART initiation until date of last
  follow-up visit.
• LTFU: absence from site of more than three months beyond
  last missed appointment date.
•     VLS: viral load < 400 copies/ml
      METHODS
       Objective 1: ART program outcomes
  Statistical methods:
• Kaplan-Meier estimates of mortality and
  retention in care calculated
• Smoothed instantaneous hazard curves of death
  and LTFU plotted using weighted kernel density
  estimates
• Multivariable competing-risks Cox regression
  and logistic regression:
  -baseline patient factors associated with death,
  LTFU and suboptimal virological response
  (< 400 copies/ml) after 6 months of ART
           Results: Objective 1
           Baseline characteristics (n= 29 319)
Median age, y (IQR)               34 (29-40)
Female, n (%)                     19 995 (68.2)
CD4 count median (IQR)            113 (57-166)
WHO stage, n (%)
 I and II                         5 326 (24.1)
 III                              13 996 (63.5)
 IV                               2 718 (12.3)
Year of enrolment, n (%)
 2004                             1 846 (6.3)
 2005                             5 375 (18.3)
 2006                             9 514 (32.5)
 2007                             2 582 (42.9)
Province, n (%)
 Western Cape              11 673 (39.8)
 Eastern Cape                      1 583 (5.4)
 Kwazulu-Natal                     15 540 (53.0)
 Mpumalanga                        523 (1.8)
                                                                        Results
                                                                        Objective 1: ART program outcomes
                                                                200


                                                                180
                           Median (IQR) baseline CD4 cells/µL




                                                                160


                                                                140


                                                                120
                                                                        111     109                     111
                                                                                                                             118       Baseline CD4 cell
                                                                100


                                                                80
                                                                                                                                       count per
                                                                60                                                                     calendar year
                                                                40


                                                                20


                                                                  0

                                                                      2004    2005                2006                  2007
                                                                35
Proportions WHO stage IV and CD4 count<50




                                                                30

                                                                25                                             CD4 count<50 cells/µl


                                                                                                                                       Proportion with
               cells/µl (%)




                                                                20

                                                                15
                                                                                                                                       baseline CD4 < 50,
                                                                10
                                                                                                              WHO stage IV
                                                                                                                                       and WHO Stage IV
                                                                 5

                                                                 0
                                                                      2004    2005                 2006                  2007
                                                                                 Year of starting ART
                   Results
                   Objective 1: ART program outcomes
          1
                                                            Virological suppression (VLS)
          .9

          .8

          .7

          .6                                                           Retention in care (RIC)

          .5

          .4

          .3

          .2                                                  Losses to follow-up (LTFU)

          .1

          0                                                               Died
               0           6         12         18        24        30              36           42
                                          Months since start of ART


Months on ART                         12                    24                       36
Proportion with VLS(%)         86.8 (85.8-87.8)     87.5 (85.3-89.6)             87.2 (80.6-92.3)
Probability of RIC (%)         80.9 (80.4-81.4)     72.6 (71.9-73.3)             68.8 (67.8-69.8)
Proportion LTFU (%)            13.6 (13.1-14.2)    15.4 (14.5-16.4)              8.8 (6.7-11.3)
Probability of death (%)        6.3 (6.0-6.7)       7.4 (7.1-7.8)                7.8 (7.4-8.3)
                                         Results
                                         Objective 1: ART program outcomes
                    Hazard of death and LTFU
                                                                           .




                                         .012


                                          .01
         Smoothed instantaneous hazard




                                         .008
                                                                                           Loss to
                                                                                           follow-up
                                         .006


                                         .004


                                         .002
                                                                               death

                                            0
                                                0       6     12          18          24       30      36
                                                             Months since start of ART


Mortality rates: Months 0-6: 11.1 (CI: 10.5–11.7)
                                                    Months >6: 1.9 (CI: 1.8–2.0) deaths/100 person-years
               Baseline factors associated with death and
               loss to follow-up at 6 months (n=15 476)
                        Death; HR (95% CI)   Loss to follow-up; HR (95% CI)
WHO stage
   I/II                         1                       1
   III                  1.61 (1.29-2.00)     1.02 (0.89-1.18)
   IV                   4.34 (3.38-5.58)     1.68 (1.38-2.04)
Baseline CD4 count
   ≥ 200                        1                       1
   50-199               1.61 (1.09-2.38)     1.28 (0.98-1.67)
   25-49                3.61 (2.40-5.45)     1.77 (1.31-2.40)
   <25                  4.63 (3.10-6.92)     1.89 (1.40-2.54)
Year of starting ART
   2004                        1                        1
   2005                 0.92 (0.70-1.22)     3.02 (1.85-4.96)
   2006                 0.72 (0.54-0.96)     4.65 (2.84-7.61)
   2007                 0.52 (0.38-0.71)     5.83 (3.55-9.57)
Province
   Western Cape                 1                       1
   Eastern Cape         2.65 (1.69-4.16)     0.78 (0.54-1.13)
   Kwazulu-Natal        2.03 (1.67-2.46)     1.22 (1.04-1.44)
   Mpumalanga           2.44 (1.46-4.09)     1.98 (1.28-3.06)
          Baseline factors associated with suboptimal
          virological response (≥400copies/ml) at 6
          months (n= 6 638)
                      O.R. (95% CI)        P – value
Age (years)
   16-19              4.10 (1.85-9.15)     0.001
   20-29                    1
   30-39              0.86 (0.72-1.03)     0.119
   40-49              0.62 (0.48-0.78)     <0.0001
WHO Clinical stage
   stage I/II               1
   stage III          1.19 (0.99-1.45)    0.063
   stage IV           1.04 (0.77-1.39)    0.804
Baseline CD4 count
   ≥100                     1
   50-199             1.03 (0.84-1.26)   0.775
   25-49              0.96 (0.73-1.27)   0.789
   <25                0.89 (0.67-1.18)   0.410
Province
   Western Cape              1
   Eastern Cape       2.35 (1.55-3.58) <0.0001
   Kwazulu-Natal      1.82 (1.48-2.23) <0.0001
   Mpumalanga         5.56 (3.40-9.13)a <0.0001
                                                   Results
                                                   Objective 1: ART program outcomes
                                             Virological suppression of adolescents
                                             100
Proportion with viral load suppression (%)




                                              90                          Age 20+ yrs
                                                         88.2
                                                                                         86.6


                                              80

                                                         75.0

                                              70
                                                                      Ages 16-19 yrs     68.2


                                              60
                                                          P = 0.001                          P < 0.0001

                                              50
                                                                6                       12
                                                                        Months on ART
                                                                    Results
                                                                    Objective 1: ART program outcomes
Proportion with missing Viral Load results at 6 months




                                                         70

                                                         60

                                                         50
                                                                                                                         Missing 6m
                                                         40
                                                                                                                         viral load
                                                         30

                                                         20
                                                                                                                         (%) by
                                                         10
                                                                                                                         province
                                                         0
                                                              Eastern Cape   Western Cape   Kwazulu-Natal   Mpumalanga
                                                         60
Proportion with missing Viral Load at 6 months




                                                         50

                                                         40                                                              Missing
                                                                                                                         6m viral
                                                         30
                                                                                                                         load (%)
                                                         20
                                                                                                                         by year
                                                         10

                                                         0
                                                                 2004            2005           2006           2007
       METHODS
       Objective 2: Comparison with other programs


• Literature review of ART program outcomes in
  low-income and high-income settings.
• Calendar years of patient follow-up: potential
  confounder when comparing outcomes.
• ARK-assisted site subset used for comparisons:
  patients enrolled & followed until March 2006.
• Most comparative published studies followed
  patients up till similar time.
                   Results
                   Objective 2: Comparative programs
                                                                                       No.     Months      Dates of
                                                Year of                     Patients   of      of follow   patient
Study Code               Reference              publications   Region       included   sites   up          observation
                                                                                                           01/2004-
ARK                                                            RSA          7,223      27      24          03/2006
                         Braitstein (5),
Low-Income countries     Keiser (6, 7)          2006-          Africa/ Asia/                               2001-
(ART-LINC)               Brinkhof (2)           2008           S America     36,715 18         12          2005
Sub-Saharan African                                            Sub-Saharan                                 1996-
retention                Rosen (4)              2007           Africa        74,289 33         9.9         2005/06
                                                               Western                                     2001-
W. Cape DOH              Boulle (1)             2008           Cape          12,587 43         48          03/2006
                         Van Cutsem (3),        2007,                                                      2001-
MSF Khayelitsha          Boulle (8), (9)        2008           Cape Town    3,373      3       60          09/2006
                         Bekker (10), Lawn      2006,                                                      09/2002-
Gugulethu                (11, 12)               2007           Cape Town    1,139      1       36          08/2005
                         Keiser (7),                                                                       1995-
Swiss HIV cohort         Ledergerber (14)       2008           Europe       2,674      5       24          2006
                         Braitstein(5),Sterne
Europe/N America (ART-   (15), May(16),         2006,          Europe/ N                                   1995-
CC)                      Egger (17)             2007           America      22,217 12          24          2004
                                  Results
                                  Objective 2: Comparisons with other programs

                        Retention in care
                        100

                                                                                      ARK-assisted sites
                                                             90.0
                        90                                                     88.2
                                                                                                    87.0
                                                                                                      Gugulethu
Remaining in care (%)




                                                                                                      Khayelitsha
                        80
                                             ART-LINC                                              WCape DOH
                                             2000-04
                        70



                        60
                                                                                               Sub-Saharan
                                                                                               24m average
                                                                                               meta-analysis
                        50                                                                     (Rosen)
                                                 worst 12m report (Uganda)

                        40
                              0          6                   12                18                    24
                                                        Months since start of ART
                                        Results
                                        Objective 2: Comparisons with other programs

                                    Cumulative mortality

                           18
                                                                                           W. Cape DOH
                           16
Cumulative mortality (%)




                           14                                Gugulethu & Khayelitsha

                           12

                           10                                                               ART-LINC

                           8                                                                           7.4
                                                                                7.1
                                                            6.3
                           6                 5.0                                       ARK-assisted sites

                           4                                           Swiss HIV cohort
                                                                                             Europe and
                           2                                                                 N America

                           0        0
                                0            6              12                  18                     24
                                                    Months since start of ART
                                                Results
                                                Objective 2: Comparisons with other programs

                                           Loss to follow-up at 6 and 12 months
                                           25
Loss to follow up at 6 and 12 months (%)




                                                                                           19.8
                                           20




                                           15
                                                                                                      6 months
                                                                                                      12 months

                                           10




                                            5                          3.3         3.9
                                                         2.1
                                                   1.7           1.9



                                            0
                                                 ARK-assisted   WCape DOH    Khayelitsha   ART-LINC
                                                     sites
                                        Results
                                        Objective 2: Comparisons with other programs

                                   Virological suppression at 6 and 12 months
                             100


                             90


                             80
Viral load suppression (%)




                             70


                             60

                                                                                                                   6 months
                             50
                                                                                                                   12 months
                             40


                             30


                             20


                              10


                              0
                                   ARK-assisted WCape DOH   Khayelitsha   ART-LINC   Swiss cohort    Europe + N
                                      sites                                                         Am. (ART-CC)
                                                          Results; Objective 3: TB treatment comparison
                                                          ARK supported: 11 sites; 2822 patients
                                                          Non-ARK supported: 98 sites; 32 853 patients
                                        100

                                                                                                                           Proportion cured:
                                        90
                                                                 P < 0.0001         P < 0.0001          P < 0.0001
                                                                                                                            13.2% at ARK-
                                        80                                                   79.2                 80.1
                                                                          78.7                                             supported sites
                                               70.7
                                        70                                                                                 (CI 10.6-15.9%)
                                        60
                                                                ARK ≥ 6m/yr       ARK ≥ 9m/yr
P r o p o r tio n d e fa u lte d (% )




                                               non-ARK                                                 ARK 12 months/yr
                                        14

                                        12            1 1 .2
                                                                                                                           Proportion
                                        10                                                                                 defaulted:
                                         8
                                                                                                                           42.8% at ARK-
                                                                         6 .4
                                         6                                                   6 .1                 5 .9     supported sites
                                         4
                                                                P < 0 .0 0 0 1    P < 0 .0 0 0 1        P < 0 .0 0 0 1     (CI 33.9-50.5%)
                                         2

                                         0
                                              Non-ARK
                                                                ARK ≥6               ARK ≥               AR K 12
                                                               m o n t h s /y r   9 m o n t h s /y r    m o n t h s /y r
                                 Results
                                 Objective 3: TB Rx outcomes: Pre entry
                                 vs. post entry
                           100



                            90
                                                                    Proportion cured:
Proportion cured (%)




                                                       P < 0.0001
                            80
                                                                       21.6%
                                                         74.0
                            70
                                                                    (CI 16.7-26.7%)
                            60   60.8



                            50

                                  pre-entry         post-entry
                           18

                           16                                        Proportion
                           14    13.6
                                                                     defaulted:
Proportion defaulted (%)




                                                       P < 0.0001
                           12

                           10

                            8
                                                         9.5
                                                                        30.0%
                            6

                            4
                                                                     (CI 15.9-41.8%)
                            2

                            0
                                 pre-entry          post-entry
            Results; Objective 3: Duration of ARK
            involvement at sites and poor TB Rx
            outcome
                Treatment failure             Defaulted treatment
 Year         Odds ratio*   P-value           Odds ratio*   P-value
              (95% C.I.)                      (95% C.I.)

 2004-07         0.77       < 0.0001            0.69          < 0.0001
             (0.73–0.81)                     (0.64–0.76)

 2004             0.56      < 0.0001             0.48         < 0.0001
              (0.50–0.64)                     (0.38–0.62)

*Odds of poor outcome per additional 6 month period of ARK presence at
a site
(maximum-likelihood logit estimates for grouped data, adjusted for no. of
cases per site)
       Conclusions
• Good medium-term ART outcomes are achievable in
  multiple-site NGO-assisted primary-health facilities
• ART needs to be initiated at an earlier stage (by
  increasing access to care) to reduce early on-treatment
  mortality.
• Additional adherence support for adolescents is required
  to improve virological suppression.
• Increasing loss to follow-up as ART program expands
  needs to be addressed.
• Need to improve systems to ensure viral load results are
  made available, which may including point of care
  facilities and partnerships with private laboratories.
• Adherence-supported ART services have a significantly
  beneficial impact on TB treatment outcomes.
        Limitations of study
• Missing viral load results may result in a differential bias
  in virological suppression proportions in either direction.
• Comparisons of ART outcomes with other programs are
  hampered by differences in reporting methods used,
  baseline immunologic status, cohort selection criteria,
  duration of and calendar years of monitoring, cohort size,
  and regimen differences.
• Improvements in TB treatment outcomes are likely to be
  due to ART itself and NGO-related site interventions-the
  relative contributions of each were not measured in this
  study.
• Confounders in TB treatment outcomes eg site level HIV
  prevalence and socio-economic status were not included
  in analyses.
        Thank you!
    Acknowledgements
•   Esca Scheepers
•   Eula Mothibi
•   Anita Jason
•   Mokgadi Malahlela
•   ARK trustees, ARK UK & SA colleagues
•   PEPFAR
•   South African Department of Health

    - for support and input without whom this work
    would not have been possible.

								
To top