Cervical cancer diagnosis and CD4+ Count trajectory in HIV-infected women in north america
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Transcript of Cervical cancer diagnosis and CD4+ Count trajectory in HIV-infected women in north america
CERVICAL CANCER DIAGNOSIS AND CD4+ COUNT TRAJECTORY IN HIV-INFECTED WOMEN IN NORTH AMERICAAlison Abraham, PhDDepartment of EpidemiologyJohns Hopkins Bloomberg School of Public Health
AG Abraham, S Gange, Y Jing, R Bosch, JT Brooks, R Dubrow, J Eron, K Gebo, MJ Gill, N Hessol, R Hogg, M Kitahata, M Klein, R Moore, S Rourke, M Silverberg, &G D’Souza, for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
IAS 2010Vienna, Austria
WEAB0104
IAS 2010 - Vienna, Austria – Oral Abstract WEAB0104
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Cervical cancer and HIV Human papillomavirus (HPV) is a
common sexually transmitted infection causally linked to cervical cancer
Most cervical HPV infections clear but in some women they persist and cause cervical cancer
Chronic immunosuppression in HIV-infection may promote HPV persistence and increase the risk of cervical cancer
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This study explored whether lower CD4 counts over time could result in higher risk of progression to cervical cancer
Does chronic immunosuppression contribute to cervical cancer risk?
NA-ACCORD is a collaboration of over 20 existing HIV research studies and>110,000 subjects
Part of the NIH/NIAIDIeDEA Network
North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
Gange, Kitahata, Saag, …, & Moore. Int J Epi 2007
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Study Design &Population HIV-infected women from 13 North American
cohorts contributing to NA-ACCORD Clinical and interval cohorts
Nested case-control study Cases: Invasive cervical cancer
Clinically confirmed or cancer registry-linked cervical cancer diagnoses
Occurring after ART initiation Controls: Women without ICC diagnosis over
follow-up
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Methods Controls were matched at ART initiation on:
CD4+ cell count, Age, Cohort, Calendar Year, Follow-up time
All controls which met the matching criteria were included to maximize available CD4 trajectory information
We modeled trends in average CD4 counts using: Piecewise-linear mixed effects models Spline terms added at ART initiation and one year
following initiation Interaction terms to describe differences between cases
and controls
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Characteristics at ART initiation
Invasive Cervical Cancer Cases (N=56)
Controls(N=503)
Median [IQR]Age 40 [33-45] 40 [36-46]Median [IQR] CD4 242 [87-353] 230 [83-328]Median [IQR] HIV RNA
4,869 [658-54,277] 2,360 [<300-54,027]
African American 55% 57%Inj. drug use Hx 29% 37%NRTI use prior to ART
23% 26%
Type of ART: PI-based 45% 49% NNRTI-based 39% 36%No statistically significant differences were noted IAS 2010 - Vienna, Austria – Oral Abstract WEAB0104
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Areas under the CD4 Curve for Cases approximately
80% of Controls
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Months from ART Initiation
CD4+
Cou
nt (c
ells/
μl)
ControlsCases
Mean CD4 and 95% CI
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Estimated CD4 trajectories
Parameter Control (95% CI)
Control - Case (95% CI)
Mean CD4 at ART (cells/μl) 250 (201, 299) 10.9 (-40.5, 62.3)
CD4 Slope (cells/μl per month)
-4 years to 0 [ART Initiation]
-1.4 (-2.2, -0.5) -3.6 (-6.3, -0.9)*
0 to 1-year post-ART 9.4 (8.2, 10.5) 8.1 (3.7, 12.4)*
1-year post-ART to ICC 2.3 (1.5, 3.1) 1.6 (2.5, 5.8)*p<0.05 for test of equality of case and control parameters IAS 2010 - Vienna, Austria – Oral Abstract WEAB0104
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Modeling CD4 trajectory
Time point Difference in mean CD4 count
Controls - Cases
4 years pre-ART 163 (29, 296)*
1 year pre-ART 32 (-25, 90)
1 year post-ART 43 (-17, 102)
2 years post-ART 96 (5, 188)*
4 years post-ART 164 (46, 282)**p<0.05 IAS 2010 - Vienna, Austria – Oral Abstract WEAB0104
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Viral Load Changes Appeared Similar
No significant differencesin the geometric mean viral
loads at any time point tested
Months from ART Initiation
Vira
l Loa
d (lo
g ba
se 1
0), c
opie
s/m
l
ControlsCases
Geometric mean VL and 95% CI
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Average CD4 counts were consistently lower over time for women who developed ICC than for similar women who remained free of ICC over follow-up
These differences in CD4 trajectory between cases and controls suggest a role of long-term immunosuppression
Less robust rebound in CD4 following ART was not explained by differences in viral load (adherence) or prior NRTI exposure (resistance)
Conclusions
13 Large study of cervical cancer among HIV-infected
women The size of NA-ACCORD allowed for both large numbers of
cases to be found and the ascertainment of appropriate controls for the current study
Rigorous quality assurance protocol to assemble data from different cohorts into single dataset Validated data on CD4 history for cases and controls for
evaluating trajectory differences Limited covariate information
No information on Pap screening (potentially heterogeneous between cohorts) or hysterectomy
Strengths and Limitations
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14NA-ACCORD cohorts: VACS: Robert Dubrow, Yale University ALLRT: Ronald Bosch, Harvard; Constance Benson, UCSD; Ann Collier, UW Seattle Montreal: Marina Klein, Montreal Chest Institute HIV Clinic, McGill University HIVRN: Kelly Gebo, Johns Hopkins School of Medicine HOPS: John T. Brooks, CDC JHHCC: Richard Moore, Johns Hopkins School of Medicine KPNC: Michael Silverberg & Michael Horberg, Kaiser Permanente Northern California SAC: M. John Gill, University of Calgary, Southern Alberta UCHCC: Joseph Eron & Sonia Napravnik, University of North Carolina, Chapel-Hill UW: Mari Kitahata, University of Washington at Seattle HOMER:RobertHogg, BC Centre for Excellence and HIV/AIDS; Simon Fraser University OHTN Sean Rourke & Anita Rachlis, University of Toronto, Canada WIHS: Nancy Hessol, UCSF, Women’s Interagency HIV StudyTHANKS TO: National Institute of Allergy & Infectious Diseases, with supplemental
funding from the National Cancer Institute
Acknowledgements
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