Hormonal contraceptive use and hiv progression a systematic review
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Hormonal contraceptive use and HIV progression: A systematic review. Sharon Phillips, MD MPH Department of Reproductive Health and Research World Health Organization Kate Curtis, PhD Division of Reproductive Health, CDC Chelsea Polis, PhD Office of Population and Reproductive Health

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Hormonal contraceptive use and HIV progression: A systematic review

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Hormonal contraceptive use and hiv progression a systematic review

Hormonal contraceptive use and HIV progression: A systematic review

Sharon Phillips, MD MPH

Department of Reproductive Health and Research

World Health Organization

Kate Curtis, PhD

Division of Reproductive Health, CDC

Chelsea Polis, PhD

Office of Population and Reproductive Health

United States Agency for International Development


Need for comprehensive reproductive health services among women living with hiv

Need for comprehensive reproductive health services among women living with HIV

  • Women living with HIV who desire children should have support to safely conceive and deliver

  • Substantial unmet need for contraception and unintended pregnancy among women living with HIV

  • All women who wish to prevent pregnancy deserve access to voluntary family planning services


Key questions

Key Questions

Are women living with HIV who use hormonal contraception at increased risk of:

  • Death or progression to AIDS

    • Measured by CD4 <200, initiation of ART, or clinical AIDS

  • Change in CD4 or viral load


Hormonal contraceptive use and hiv progression a systematic review

Methods


Methods study selection

Methods: Study selection

  • Primary reports of studies examining hormonal contraceptive use among women living with HIV

  • PUBMED and EMBASE searched for published articles in any language through December 15, 2011

  • 634 unique references identified, 16 full-text articles assessed, 12 reports included

  • Excluded: studies with no comparison group; case control studies

  • Study information independently abstracted by 2 authors (SP & KC)


Methods quality criteria

Methods: Quality criteria

  • Methodology used to minimize confounding

  • Accurate measurement and analysis of exposure

  • Composition of comparison group

  • Loss to follow-up

  • Length of follow-up

  • Additional considerations for RCTs

    • Adequate randomization

    • Allocation concealment

    • Distribution of potential confounders between groups

    • Maintenance of comparability of groups


Hormonal contraceptive use and hiv progression a systematic review

Results


Results

Results

  • 12 reports (of 11 studies) met inclusion criteria

    • 1 RCT (2 reports)

    • 10 observational

  • Outcomes considered

    • Mortality or progression to AIDS

    • Change in CD4 or viral load


Outcome 1 mortality or progression to aids

Outcome 1: Mortality or progression to AIDS

  • 9 reports of 8 studies

  • 1 RCT (2 reports), 7 observational studies


1 mortality or progression to aids

1. Mortality or progression to AIDS

RCT: Stringer et al., 2007/2009 reanalysis

Designed to assess safety of IUD in women living with HIV

  • 599 postpartum women living with HIV, Zambia

  • Randomized to either copper IUD or hormonal contraception (choice of OCs or DMPA)

  • 2 year follow-up, 6 month visits

  • High loss to follow-up rates

    • 31% of hormonal group, 23% of IUD group

  • High method discontinuation/switching rates

    • 49% of IUD users discontinued, 76% of these switched to HC

    • 13% of hormonal users discontinued, 16% switched to IUD

    • Within hormonal group, 34% switched between OC and DMPA


1 mortality all cause or progression to aids

1. Mortality (all cause) or progression to AIDS

Stringer 2007/2009 RCT (continued): HR (95% CI)


1 mortality or progression to aids cohort

1. Mortality or progression to AIDS (Cohort)

*Except Allen 2007 (HIV-related mortality only)


Hormonal contraceptive use and hiv progression a systematic review

Studies assessing injectables and progression to AIDS OR mortality (composite outcome) (adjusted hazard ratio)

Stringer RCT (2009)*

(DMPA vs IUD)

Stringer Multi-Country (2009)

(Inj/imp† vs no HC)

Morrison (2011)

(DMPA vs no HC)

Polis (2010)

(DMPA vs no HC)

Injectables decrease risk of progression

Injectables increase risk of progression

*Actual use analysis

† DMPA, NET-EN, implants


Studies assessing ocs and progression to aids or mortality composite outcome adj hazard ratio

Studies assessing OCs and progression to AIDS OR mortality (composite outcome) (Adj hazard ratio)

Stringer RCT (2009)*

(OCs vs IUD)

Morrison (2011)

(OCs vs no HC)

Stringer Multi-Country (2009)

(OCs vs no HC)

Polis (2010)

(OCs vs no HC)

1

OCs increase risk of progression

OCs decrease risk of progression

*Actual use analysis


Results outcomes considered

Results: Outcomes considered

  • Mortality or progression to AIDS

  • Change in CD4 or viral load


2 change in viral load cd4 5 observational studies

2. Change in viral load, CD4 (5 observational studies)


Discussion outcome 1 mortality or progression to aids

Discussion: Outcome 1Mortality or progression to AIDS

  • 7 observational studies find no association between HC and HIV disease progression

  • 1 RCT found increased rates of

    • time to CD4 count < 200 and

    • time to CD4 count < 200 and mortality

    • among HC users compared with IUD users (both OC and DMPA users)


Discussion outcome 1 mortality or progression to aids1

Discussion: Outcome 1Mortality or progression to AIDS

  • Strengths

    • Many observational studies with similar findings, 2 with very strong methodology

    • One very large study (n=7846)

  • Limitations

    • Some small sample sizes

    • Follow-up time

    • RCT:

      • loss to follow-up

      • method switching

      • comparison with IUD


Discussion outcome 2 change in viral load cd4

20

Discussion: Outcome 2Change in viral load, CD4

  • 5 observational studies find no adverse association between HC and change in viral load or CD4

  • Limitations

    • Small sample sizes

    • Failure to separate HC methods in some studies

    • Lack of control for potential confounders


Discussion study quality observational studies

21

Discussion:Study Quality – Observational studies

  • Quality ranged from poor to good

  • "Good" studies

    • Incident HIV cases

    • Multivariate analysis

    • Time-varying analysis of use of hormonal contraception

    • Findings similar to those rated as "fair" and "poor"

  • "Fair" studies

    • Prevalent HIV cases

    • Control for baseline health characteristics in multivariate model

  • "Poor" studies

    • No separate analysis of different contraceptive methods

    • Inclusion of other HC users in comparison group

    • No multivariate analysis


Discussion limitations in body of research

Discussion:Limitations in body of research

  • Minimal or no information on newer methods (LNG-IUD, patch, ring, implants)

  • Limited data for women with clinical AIDS

  • All studies observational, with the exception of 1 RCT


Conclusion

Conclusion

  • The preponderance of evidence thus indicates that use of OCs or of DMPA does not affect HIV disease progression among women with HIV


Acknowledgements

Acknowledgements

Members of the WHO Hormonal Contraception & HIV Advisory Group (manuscript review)

  • Andy Gray, Olav Meirik, & Catherine Hankins

    Assistance with project development

  • Mary Lyn Gaffield, Nathalie Kapp, & Roger Chou

    Assistance with EROS software

  • Agustin Ciapponi & Demián Glujovsky

    Assistance with literature search

  • Nellie Kamau & LaToya Armstrong

Contact: [email protected]


Studies assessing injectables and mortality adjusted hazard ratio

Studies assessing injectables and mortality (Adjusted hazard ratio)

Stringer RCT (2009)*

(DMPA vs IUD)

Kilmarx (2000)

(DMPA vs non-DMPA†)

Polis (2010)

(DMPA vs no HC method)

Stringer Multi-Country (2009)

(Imp/injvs no HC method†)

Allen (2007)

(unspec inj. vs

never used injectables)

Injectables decrease risk of mortality

Injectables increase risk of mortality

*Actual use analysis

†Mostly OCs

†DMPA, NET-EN, implants


Studies assessing ocs and mortality adjusted hazard ratio

Studies assessing OCs and mortality(Adjusted hazard ratio)

Stringer RCT (2009)*

(OCs vs IUD)

Kilmarx (2000)

(OCs vs non-OCs†)

MRC (1999)

(OCs vs other/no contraception)

Polis (2010)

(OCs vs no hormonal method)

Allen (2007)

(OCs vs never used OCs)

OCs decrease risk of mortality

OCs increase risk of mortality

*Actual use analysis

†Mostly DMPA


Studies assessing injectables and progression to aids adjusted hazard ratio

Studies assessing injectables and progression to AIDS (adjusted hazard ratio)

Stringer RCT (2009)*

(DMPA vs IUD)

Stringer Multi-Country (2009)

(Inj/imp vs no HC†)

Morrison (2011)

(DMPA vs no HC)

Kilmarx (2000)

(DMPA vs non-DMPA†)

1

Injectables decrease risk of progression

Injectables increase risk of progression

*Actual use analysis

†DMPA, NET-EN or implant

†Mostly OCs


Studies assessing ocs and progression to aids adjusted hazard ratio

Studies assessing OCs and progression to AIDS (Adjusted hazard ratio)

Stringer RCT (2009)*

(OCs vs IUD)

Kilmarx (2000)

(OCs vs non-OCs†)

Morrison (2011)

(Low dose OCs vs no HC)

Stringer Multi-Country (2009)

(OCs vs no HC)

MRC (1999)

(OCs vs other or no HC)

OCs decrease risk of progression

OCs increase risk of progression

*Actual use analysis

†Mostly DMPA


Study flow

Study Flow


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