Antiretroviral drug resistance in pregnant
women living with HIV in England & Wales:
preliminary results from the matching of three
national HIV surveillance databases
Laura Byrne, Cuong Chau, Valerie Delpech, David Dunn, Pat Tookey,
Anna Tostevin & Claire Thorne
UCL Institute of Child Health
Background
Background
• Drug resistance testing for all newly diagnosed patients recommended
since 2005 and now for virtually all pregnant women prior to
treatment
• Genetic diversity has increased in the UK, the majority of heterosexual
women have non-B subtype
• Overall, TDR peaked in the UK in 2002, has fallen and now stabilised at
8-9% in recent years
• Non-B subtypes associated with lower prevalence of TDR
• The prevalence of TDR in pregnant women has not been estimated
before in the UK
Aims
1.
Ascertain the proportion of women reported to the NSHPC who can
be matched to ≥1 resistance test in UKDRD and factors associated
with being matched
2.
Describe the distribution of HIV-1 viral subtype in pregnant women
3.
Describe the prevalence of TDR in women diagnosed during
pregnancy who are naive to ART
Methods
LINKAGE BETWEEN THREE NATIONAL HIV SURVEILLANCE
DATABASES

National Study of HIV in Pregnancy & Childhood (NSHPC) collects data on
pregnancies in all HIV-positive women and their infants

Survey of Prevalent HIV infections Diagnosed (SOPHID) part of Public Health
England’s HIV AIDS Reporting System (HARS)
•

Clinical and risk factor information on all adults seen for HIV care in NHS
sites in England, Wales and Northern Ireland
UK HIV Drug Resistance Database (UKHDRD) held at MRC CTU at UCL
•
Collects the majority of resistance tests performed as part of routine
clinical care in the UK
Methods
DATA LINKAGE

Hierarchical matching algorithm: combinations of identifiers
•
SOPHID to UKHDRD
–
•
–
e.g. patient number, site of care, soundex, region, date of birth
SOPHID to NSHPC
e.g. sex, date of birth, partial postcode, country of birth and date of HIV
diagnosis

80% of resistance tests matched to a SOPHID record

Nearly 90% of women in NSHPC matched to a SOPHID record
Methods
SUBTYPE & RESISTANCE TESTS

HIV viral subtype determined using the REGA HIV-1 subtyping tool v3.0

TDR: presence of ≥1 mutations from the WHO 2009 surveillance list
POPULATION

HIV+ women with ≤ 1 reported pregnancy due to deliver or delivering
2000-2013 reported by Sep 2014 in England & Wales
STATISTICAL ANALYSES

Fisher’s exact / chi square for comparison of proportions

Logistic regression models for factors assoc. with matched resistance test
Results
POPULATION CHARACTERISTICS

10, 115 women diagnosed before delivery with delivery date (or EDD) 20002013, reported by Sep 2014

14,416 pregnancies

Median age at conception 30 years (IQR 26 to 34)

78.0% Black African, 1.3% likely infected through IDU

Median year HIV diagnosis 2004 (range 1982 to 2013)

49.9% women matched to at ≥1 resistance test

58.2% matched if year of diagnosis > 2005

63.5% of women with a RT classified as naïve on the 1st test
Results
FACTORS ASSOCIATED WITH ≥1 MATCHED RESISTANCE TEST
Multivariable
analysis
aOR
95% CI
1 pregnancy reported
1.0
-
2 pregnancies reported
1.65
1.49 - 1.83
≥3 pregnancies reported
1.98
1.70 – 2.31
Woman diagnosed with HIV 2010-2013
1.0
Woman diagnosed with HIV 1985-1995
0.75
0.56 – 0.99
Woman diagnosed with HIV 1996-2000
0.56
0.45 – 0.69
Woman diagnosed with HIV 2001-2005
0.63
0.53 – 0.75
Woman diagnosed with HIV 2006-2009
0.94
0.80 – 1.11
Results
FACTORS ASSOCIATED WITH ≥1 MATCHED RESISTANCE TEST
Multivariable
analysis
aOR
95% CI
Woman’s ethnicity – Black African
1.0
-
Woman’s ethnicity - White
0.95
0.72 – 1.26
Woman’s ethnicity - other
1.1
0.85 – 1.44
Woman born in UK/Ireland
1.0
-
Woman born in rest of Europe
0.83
0.64 – 1.07
Woman born in Africa
0.75
0.66 – 0.86
Woman born elsewhere
0.80
0.65 – 0.98
Results
FACTORS ASSOCIATED WITH ≥1 MATCHED RESISTANCE TEST
Multivariable
analysis
aOR
95% CI
First pregnancy reported from London
1.0
-
First pregnancy reported from rest of
England
0.66
0.61 – 0.72
Year of first pregnancy reported
2009-2013
1.0
-
Year of first pregnancy reported
2000-2003
0.55
0.47 – 0.63
Year of first pregnancy reported
2004-2008
0.88
0.79 – 0.98
Results
VIRAL SUBTYPE
Woman’s region of birth (n=4929)
HIV-1 subtype
C
UK / Ireland
(654)
Europe
(193)
Africa
(3,761)
Elsewhere
(321)
TOTAL
32.9%
13.5%
52.9%
20.3%
46.6%
CRF02_AG
8.1%
7.2%
14.5%
5.3%
13.1%
A
6.8%
16.6%
11.6%
3.4%
10.6%
B
37.3%
33.2%
1.1%
46.1%
10.1%
Other recombinant forms
7.8%
10.9%
7.1%
21.5%
8.3%
G
3.7%
10.9%
5.6%
2.2%
5.3%
D
2.8%
1.0%
4.5%
1.3%
4.1%
Other pure
0.5%
5.7%
1.3%
0%
0.7%
Unclassified / complex
0.2%
1.0%
0.8%
0%
0.7%
p<0.01
Results
TDR IN WOMEN DIAGNOSED DURING PREGNANCY1
Woman’s year of diagnosis (n=1302)
TDR by drug
class
20002003
20042005
20062007
20082009
20102011
20122013
Total
P
value2
Any resistance
3.4%
7.3%
2.4%
5.2%
5.4%
10.1%
5.2%
<0.01
Any NRTI
resistance
1.1%
2.6%
0.8%
2.1%
2.0%
4.5%
1.9%
0.18
Any NNRTI
resistance
1.1%
3.9%
1.3%
1.7%
4.4%
6.3%
2.8%
0.02
Any PI resistance
1.1%
1.7%
0.8%
1.7%
0.5%
1.8%
1.2%
0.65
Number of
women with a RT
88
234
375
291
203
111
1302
1 Woman
diagnosed during the index pregnancy, classified as “ART naïve” on resistance test request, with
resistance test date within pregnancy. 2 Fisher’s exact test between years (test-for-trend not significant).
Conclusions
•
50% women in the NSHPC have been matched to ≥1 resistance test in the
UKDRD
•
Factors assoc. with being matched:
–
–
–
–
–
•
≥1 pregnancy reported
diagnosed after 2005
born in UK/Ireland or Europe vs. Africa or elsewhere
First pregnancy reported from London vs. rest of England
First pregnancy reported in later time period
Matching between SOPHID & NSHPC is reliant on partial postcode, therefore
more mobile populations may be less well matched
Conclusions
•
Nearly 50% subtype C infection, only 10% subtype B, underlining viral
diversity in HIV+ people in the UK and the association with risk type and
region of birth
•
Overall prevalence of 5.2% in pregnant women in keeping with previous
estimates of TDR in heterosexual popn in the UK
•
Most common TDR drug class was NNRTIs followed by NRTIs, and prevalence
of TDR to PIs was very low
•
Numbers of women diagnosed during pregnancy have steadily dropped since
a peak in 2004-2007. However, suggestion that the prevalence of TDR in
pregnant women may have increased in the most recent time period
Acknowledgments
NSHPC Ethics
MREC/04/2/009
NSHPC Current funding
Public Health England
The National Screening Committee
Additional funding
LB currently holds MRC Clinical Research
Training Fellowship
NSHPC Current team
Principal investigator: Pat Tookey
Data manager & statistician: Helen Peters
Researchers: Kate Francis, Angela Jackson,
Laura Byrne
Administrative assistant: Icina Shakes
Additional support: Claire Thorne, Catherine
Peckham, Mario Cortina-Borja
www.ucl.ac.uk/nshpc
Acknowledgements
Shema Tariq & Clare French, former PhD
students at NSHPC who helped set-up the
matching between SOPHID & NSHPC with
Cuong Chau and colleagues at PHE