Hormonal Contraception Use and Non-AIDSdefining

Transcription

1 Hormonal Contraception Use and Non-AIDSdefining Events Vlada Melekhin, MD, MPH January 10, 2012 Vanderbilt University

2 Outline Background Methods Results Conclusions Limitations Future Directions

3 Hormonal Contraception and HIV disease (1) Higher risk of HIV disease progression Randomized Clinical Trial, Zambia Stringer et al. AIDS 2009 Observational data, Kenya Baeten et al. JAIDS 2005

4 Hormonal Contraception and HIV disease (2) Lower risk of HIV disease progression Observational data, Asia, Rwanda, Uganda Polis et al. AIDS 2010 Allen et al. J Women s Health 2007 Stringer et al. AIDS 2009

5 Hormonal Contraception and Metabolic Complications HIV-negative, Observational data Elevates LDL and lowers HDL Leads to insulin-resistance and impaired glucose tolerance Coagulation factors Sitruk-Ware et al. Rev Endocr Disord 2011

6 HIV and Non-AIDS-defining events (NADE) RCT and Observational Cardiovascular Renal Hepatic Metabolic Non-AIDS-related malignancies Multifactorial (ARV, demographics, lifestyle, persistent viral replication, etc.) Obel et al. CID Belloso et al. HIV Med Wester et al. AIDS 2011.

7 Aim and Hypothesis Aim Assess effect of Hormonal Contraception (HC) use on AIDS-defining events (ADE), NADE, and death Hypothesis HC use will lead to a lower risk of ADE and a higher risk of NADE

8 Design Retrospective Cohort Study, Inclusion Criteria yo Exclusion Criteria: History of pulmonary embolus/deep venous thromboembolism Hysterectomy +/- bilateral tubal ligation Breast cancer Pregnancy ACOG practice bulletin. No. 73, 2006

9 ADE 1993 CDC criteria NADE Metabolic Hepatic Renal Cardiovascular Outcomes Non-AIDS-related malignancies Death

10 Definitions Exposure > 30 day HC use (oral, patch, injectable) Follow-up 1 st clinic/1 st HC use to 1 st ADE, NADE, or death Baseline +90 days from 1 st clinic/1 st HC use

11 Statistical Methods Cox Proportional Hazards Model Propensity score for HC use Variables: age, race, year of cohort entry, baseline CD4/CD4%/HIV RNA, CD4 nadir, h/o ADE/non-ADE, h/o IDU/non-IDU, h/o HCV, current smoking, prior HAART/ART use, current HAART use (during baseline period), baseline hemoglobin, time from 1st clinic until 1st hormonal contraceptive use

12 Results Numbers are like people: torture them enough and they'll tell you anything.

13 Study Population (N=467) 112 HC Use No HC Use 355

14 HC users: Younger (P<0.001) Median Age (years) HC use No HC use

15 HC users: Higher CD4+ (Ps<0.01) HC use Median C D4+ count Median C D4+ nadir No HC use (cells/mm 3 )

16 HC users: Lower HIV-1 RNA (P<0.001) HC use No HC use 0 Median HIV-1 R NA (log10 copies/ml )

17 HC users: Lower HCV and Non- IDU rates (Ps<0.03) 30% 27% 25% 20% 15% 16% 15% 10% 5% HC use 5% 0% HCV Non-IDU No HC use

18 HC Users: No statistical differences in HAART use 30% 30.4% 26.8% 20% HC Use No HC Use 10% 0% HAART use

19 HC users: No statistical difference in prior ADE & NADE 38% 40% 25% 30% 20% 13% HC use 10% 5% No HC use 0% h/o ADE h/o NADE

20 HC categories (N=112) O ral N=51 Inject able N=61

21 HC Use Duration, months (P=0.26) Oral Injectable 2 0 Median HC duration

22 HC Users: longer follow-up, years (Ps<0.01) Median follow-up, ADE Median follow-up, NAD E Median follow-up, Death HC use No HC use

23 HC Users: more of new NADEs & fewer deaths (*Ps<0.03) 40% 30% 20% 10% 0% 11% 12% 14% ADE ADE /death 34% 32% 30%* 21% 20% 6% NADE NADE /death D eath 15%* HC use No HC use

24 HC Users: more new Cardiovascular NADEs (*P=0.02) 15% 12%* 10% 8% 5% 6% 6% 5% 4% 3% 5% 0% CV H epatic Metabolic Renal Malignancy 1% 0.3% HC use No HC use

25 HC users: higher risk of NADE & NADE/death P=0.3 P=0.4 P=0.3 P=0.02 P= Hazard Ratio 1 0 ADE ADE/death NADE NADE/death Death

26 Injectable HC users: higher risk of NADE & NADE/death P=0.8 P=0.3 P=0.3 P=0.03 P= Hazard Ratio ADE ADE/death NADE NADE/death Death

27 Oral HC users: higher risk of NADE P=0.1 P=0.3 P=0.02 P=0.4 P= Hazard Ratio ADE ADE/death NADE NADE/death Death

28 Limitations Retrospective cohort, residual confounding No measure of HC adherence No osteoporosis or BMI Potentially shortened follow-up among HC users

29 Conclusions HC users healthier at baseline High rates of NADE at baseline in both groups Higher risk of NADE and NADE/death in HC users

30 Future Directions Marginal Structural Model HC use and ART use as time-varying variables Osteoporosis to NADEs Baseline BMI Larger Cohort

31 Acknowledgements Tim Sterling Bryan Shepherd Cathy Jenkins Megan Turner Sam Stinnette Peter Rebeiro Sally Bebawy Dan Rasbach CCC staff and patients Epi/Outcomes group Funding: Vanderbilt-Meharry CFAR (P30) AI54999 K24 A NRSA Institutional Research Training Grant (T32) K23 AI080227