Trends over calendar time in antiretroviral treatment success and failure in HIV

clinic populations

Background

• Antiretroviral therapy (ART) has led to major improvements in the health of HIV infected populations

• Key indicators of this success include the proportion of patients on therapy with viral load (VL) <50 copies/mL and the proportion of all patients with a low CD4 count (<200 /mm3)

• However, an increasing number of patients have experienced extensive triple class failure (ETCF)

Objectives

• To present trends over time in key indicators of treatment success and failure in the UK CHIC Study

• To estimate similar UK wide trends

Methods (1)

• The number of patients under follow-up in UK CHIC in each year from 2000-2008 was calculated

• Patients were defined to be ART experienced in a given year if they had started ART before July 1st

• The proportion of patients with CD4 count <200 cells/mm3 and VL <50 copies/mL on July 1st of each year was also calculated

Methods (2)

• Virologic failure of a drug was defined if a viral load >500 copies/mL was measured in an individual, despite at least 6 months of continuous use of the drug

• Extensive triple class failure (ETCF) was defined as failure of at least 3 NRTIs, an NNRTI and a PI/r

• CHIC estimates (risk group specific) were multiplied up to UK-wide estimates based on the breakdown of risk group from SOPHID

UK CHIC – 12 Centres

Centre Number of patientsBrighton 2,772Mortimer Market/Archway 5,904St. Mary’s 5,188Kings 3,461Chelsea and Westminster 10,286Barts and the London 3,717Royal Free 4,150Edinburgh Western General 1,012Homerton 1,247North Middlesex 1,494Bristol 1.026Leicester 625Number of patients included in dataset

- Before de-duplication 40,882- After de-duplication 35,377

Characteristics of cohort

n %

Total number of patients 35377 100.0

Sex: Female 8659 24.5

Risk group: MSM 17984 50.8IDU 1396 4.0Heterosexual 11149 31.5Other/not known 4848 13.7

Ethnicity: White 19912 56.3Black African 8543 24.2Other 4711 13.3Not known 2211 6.3

Median (IQR) age at first entry into cohort (years): 30 24-36

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Patients under follow up in UK CHIC

2000 2001 2002 2003 2004 2005 2006 2007 2008

No. under follow-up 9008 10184 11359 12702 13915 15212 17022 17612 17023

% Male 83 81 80 78 77 76 76 76 76

% MSM 66 64 62 61 60 59 59 58 57% Heterosexual 23 26 28 30 31 32 32 33 32

ART experienced (N) 6977 7907 8775 9871 10924 11977 13566 14336 13993

% NNRTI experienced 64 72 76 78 81 81 80 79 81% PI experienced 63 59 57 54 55 56 56 58 56

% 3-class

experienced

35 38 38 38 39 39 39 39 38

Proportion of patients with current CD4 <200 cells/mmProportion of patients with current CD4 <200 cells/mm33 and and proportion of patients on HAART with VL<50 copies/mlproportion of patients on HAART with VL<50 copies/ml

0

10

20

30

40

50

60

70

80

90

100

2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

Pro

po

rtio

n o

f p

ati

en

ts

On ART,VL<50copies/ml

CD4<200cells/mm

ART regimens received – all patients under follow upART regimens received – all patients under follow up

0

20

40

60

80

100

2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

% o

f p

atie

nts

on

HA

AR

T

Sixth+

Fifth-line

Fourth-line

Third-line

Second-line

First-line

ART regimens received – ART regimens received – ART-naïve patients, CD4 >200 cells/mm3 at start

0

20

40

60

80

100

2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

% o

f p

atie

nts

on

HA

AR

T

Sixth+

Fifth-line

Fourth-line

Third-line

Second-line

First-line

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL >50 copies/ml

%

24 24 40 49 58

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL <50 copies/ml

%

24 24 40 49 58

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL <50 copies/ml

%

24 24 40 49 58

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL <50 copies/ml

%

24 24 40 49 58

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL <50 copies/ml

%

24 24 40 49 58

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL <50 copies/ml

%

24 24 40 49 58

Estimated UK trends

Year 2000 2002 2004 2006 2008

No. under follow-up 20,384 28,265 37,999 47,723 56,433

On ART (N) 14,004 19,558 27,031 35,735 43,635

VL<50 copies/ml % 60 67 80 85 87

CD4<200 cells/mm3 % 20 15 13 10 7

ETCF (N) 132 483 985 1375 1829

Of which VL <50 copies/ml

%

24 24 40 49 58

ETCF in the UKETCF in the UK

0

200

400

600

800

1000

1200

1400

1600

1800

2000

Year under follow-up

Nu

mb

er

of

pa

tie

nts

ETCF,observed

VL<50copies/mL,observed

Summary

• ART success has improved markedly over the period 2000-2008 with around 87% of patients now having a VL <50 copies/mL

• Over 90% of all patients now have a CD4 count above the particularly high risk level of 200 cells/mm3

• The absolute number of patients with ETCF is increasing

• However, the proportion of such patients who have VL >50 copies/ml is decreasing so the absolute number of patients with ETCF and detectable virus is no longer increasing

Research Department of Infection and Population Health, UCL Medical School: Caroline Sabin, Teresa Hill, Loveleen Bansi, Andrew Phillips, Susie Huntington

Medical Research Council Clinical Trials Unit (MRC CTU): Abdel Babiker, David Dunn, Adam Glabay, Kholoud Porter

Brighton and Sussex University Hospitals NHS Trust : Martin Fisher, Duncan Churchill, Nicky Perry, Anthony Pullin

Chelsea and Westminster NHS Trust: Brian Gazzard, Steve Bulbeck, Jemima Clarke, Sundhiya Mandalia

Kings College London School of Medicine, GKT Hospitals: Frank Post, Philippa Easterbrook, Yasar Khan, Paragi Patel, Fatimah Karim, Stephen Duffell, Fowzia Ibrahim

Mortimer Market Centre, UCL Medical School: Richard Gilson, Shuk-Li Man, Ian Williams

Royal Free NHS Trust/UCL Medical School: Margaret Johnson, Clinton Chaloner, Helen Grabowska, Fiona Lampe, Dewi Ismajani Puradiredja, Mike Youle, Colette Smith

Imperial College Healthcare NHS Trust: John Walsh, Nicky Mackie, Alan Winston, Christian Kemble, Jonathan Weber

Barts and the London NHS Trust: Chloe Orkin, Kevin Jones, Rachel Thomas

Homerton University Hospital NHS Trust: Jane Anderson, Sajid Munshi

The Lothian University Hospital NHS Trust: Clifford Leen, Alan Wilson

North Middlesex University Hospital NHS Trust: Achim Schwenk, Jonathan Ainsworth

Health Protection Agency Centre for Infections: Valerie DelpechNorth Bristol NHS Trust: Mark Gompels, Debbie Dooley

UK CHIC is funded by the UK Medical Research Council

UK CHIC: Acknowledgements