Long term follow-up on ARV treatmentOutcomes and challenges at 48 months in

Khayelitsha ,South Africa

Provincial Government of the Western Cape

Infectious Disease Epidemiology Unit, University of Cape Town

Médecins Sans FrontièresMSF Scientific day,June 1st 2006

- the experience in Khayelitsha- the experience in Khayelitsha

Khayelitsha townshipKhayelitsha township• Peri-urban township ~

500.00 inh.

• PMTCT started in 1999, HIV clinics in 2000 and ARV in 2001

• HIV antenatal rate ~ 30 % and TB incidence at 1750/100.000

• TB/HIV co-infetion rate at 72%

• ~ 8000 patients on active file including 3800 patients on ARV

Khayelitsha Antenatal HIV PrevalenceKhayelitsha Antenatal HIV Prevalence 1999-20051999-2005

10%

15%

20%

25%

30%

35%

J an-Mar

1999

Oct-Dec J ul-Sep Apr-J un J an-Mar

2002

Oct-Dec J ul-Sep Apr-J un J an-Mar

2005

Oct-Dec

Mean Prevalence (95 % CI)

Impact of the scaling up strategyImpact of the scaling up strategy

Number of new patients started on ART per year

Median CD4 count on starting (IQR) by year of starting

84237

419

1138

1831

0

500

1000

1500

2000

2001 2002 2003 2004 2005

48

7385

105

41.5

0

20

40

60

80

100

120

140

160

180

2001 2002 2003 2004 2005

Children 0-14 years Children 0-14 years ART initiation by yearART initiation by year

17 2038

531517

32

48

3

1

0

20

40

60

80

100

120

2001 2002 2003 2004 2005

Nu

mb

er

sart

ed

on

AR

T

boys girls

Vertical transmission rate measured at 8.8 % (.PCR survey 2004, n=500)

Mortality at 3,6,12 and18 months Mortality at 3,6,12 and18 months according to year ART initiatedaccording to year ART initiated

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

2001 2002 2003 2004 2005

Perc

ent d

ied 3 m

6 m

12m

18m

Median Cd4 cells counts at different time Median Cd4 cells counts at different time points points

Khayelitsha 2001-1005 n=3152

81

229271 239

303372 380

460

0

100

200

300

400

500

600

CD

4 ce

ll co

unt

chan

ge (

med

ian

IQR

)

Proportion of undetectable VL Proportion of undetectable VL ( < 400 copies/ml) ( < 400 copies/ml)

Khayelitsha 2001-1005 n=3152

0%

20%

40%

60%

80%

100%

0 3 6 12 18 24 30 36 42 48

Months on ART

Retention in care at 48 monthsRetention in care at 48 months(on first and second lines)(on first and second lines)

60%

65%

70%

75%

80%

85%

90%

95%

Months on ART

93% 90.20% 86.60% 84% 80.5% 80.6% 78.3% 77.6% 75.6%

3 6 12 18 24 30 36 42 48

Lost to follow-up by time period according to Lost to follow-up by time period according to

year ART initiatedyear ART initiated

0 04

11

35

0 04

20

31

0

5

10

15

20

25

30

35

40

2001 2002 2003 2004 2005

Num

bers

LTF

3 months 6 months

Substitutions due to toxicity by drugSubstitutions due to toxicity by drug

nChanged by 36 months (%, 95% CI)

d4T 1228 1065 471 113 18 9 5 16.5 (12.0-22.6)AZT 639 497 442 417 306 205 132 8.3 (6.3-10.9)NVP 977 828 385 129 104 89 63 7.4 (5.4-10.1)EFV 967 790 558 423 245 139 81 3.1 (1.8-5.5)

0.00

0.05

0.10

0.15

0.20

0 6 12 18 24 30 36Duration on drug in months

Kaplan-Meier failure estimate

d4T

AZT

NVP

EFV

Pro

por

tion

subs

titut

ed d

ue t

o to

xici

ty

13th Conference on Retroviruses and Opportunistic Infections, Denver 2006

Causes of toxicity-driven substitutions on D4TCauses of toxicity-driven substitutions on D4T

Lactic acidosis / symptomatic hyperlactataemia

0.00

00.

025

0.05

00.

075

0.10

0

0 6 12 18 24 30 36

Duration on stavudine in months

Kaplan-Meier failure estimate

Peripheral neuropathy

Other toxicities incl. lipodystrophy

Pro

por

tion

subs

titut

ed d

ue t

o to

xici

ty

Hyperlactataemia/LA 1228 1074 484 118 20 11 6 8.7 (5.3-14.0)Peripheral Neuropathy 1228 1068 486 120 19 9 5 6.4 (4.0-10.2)

Other 1228 1073 495 123 21 11 6 1.7 (0.6-4.6)

nChanged by 36mo

(%, 95% CI)Reason for subst.

Combined 1228 1065 471 113 18 9 5 16.5 (12.0-22.6)

13th Conference on Retroviruses and Opportunistic Infections, Denver 2006

Rate of substitutions due to symptomatic Rate of substitutions due to symptomatic hyperlactataemia/lactic acidosishyperlactataemia/lactic acidosis

30 2

60

17

81

44

316

0

100

200

300

400

500

Every

one

< 6

mon

ths

>= 6

mon

ths

Men

>=

6 m

onth

s

Wom

en >

= 6

mon

ths

Wom

en<

75kg

, >=

6 m

onth

s

Wom

en >

= 75

kg, >

= 6

mon

ths

Rat

e pe

r 10

00py

13th Conference on Retroviruses and Opportunistic Infections, Denver 2006

Proportion of patients on second lineProportion of patients on second line

4.2%

0.6%

11.0%

17.8%

0%2%4%6%8%

10%12%14%16%18%20%

12 (1419) 24 (500) 36 (209) 48 (56)

Months on ART (n=)

Cu

m %

on

2n

d l

ine

• Regimen change on virological failure defined as 2 consecutive measures > 5.000 copies/ml

• Each complete regimen interruption (for AE, CI or hospitalisation) results in increased risk of virological failure (AHR 3.2 [95% CI 2.0-5.1], p<0.001), controlled for baseline CD4 count.

Needs coverage Needs coverage

• Inclusion rate needs to reach 3200 new patients/year by 2010

• Cumulative :3800 patients on HAART now while estimated 15.000 patients by 2010

• Based on existing 3 clinics model, > 5000 patients/clinic by 2010

• Based on existing doctor/nurses ration, unfeasible0

500

1000

1500

2000

2500

3000

3500

19

85

19

87

19

89

19

91

19

93

19

95

19

97

19

99

20

01

20

03

20

05

20

07

20

09

20

11

20

13

20

15

Demand at 70%Started ART

Source : ASSA model 2003

Monitoring and evaluation : a triangular relation between Monitoring and evaluation : a triangular relation between clinic staff , Cape Town University and MSFclinic staff , Cape Town University and MSF

Real time clinical records capture in each clinic fter

each visit (dedicated clerk)

Data cleaning / integration of lab records

Monthly activity report

Quarterly outcomes cohort report

Retrospective database analysis for specific operational research

questions

Daily patient bookings

Daily missed appointment and weekly defaulters list

Clinic staff University of Cape Town /MSF epidemiologist

Conclusions Conclusions

• More than 75 % of initial patients are still in care at 48 months including 18 % on 2nd line :while numbers starts to grow,there is no affordable and patient friendly second line available

• While scaling up , challenges of managing large teams and initial signs of staff burn require innovative radical solution to cope with projected workload by 2010

• Long term D4t related toxicity requires an urgent revision of our guidelines

• Universal access is possible in such high prevalence setting but tight monitoring together with reactive management lines are essential for ongoing adaptation of service with such explosive growth

• Partnership for operational research in with UCT had a major influence on national policies and guidelines .It has improved MSF operational research standards and made results acceptable in a politically sensitive context

AcknowledgementsAcknowledgements• Patients and staff at HIV clinics

• Monitoring and evaluation team : University of Cape Town and MSF (Andrew Boulle, Katherine Hildebrand, Washifa Abrahams)

• ARV task team, Western Cape Department of Health