1. +
HIV and hormonal
contraception:
New data, ongoing
controversy
Sharon Phillips MD MPH
Medical Officer
Department of Reproductive Health and Research
World Health Organization
Geneva, Switzerland

2. + HIV and unintended pregnancy:
two important public health concerns
 17
million women globally are living with HIV
 >150
million women worldwide use a hormonal
contraceptive method
 Injectables
Africa
particularly common in sub-Saharan
 Highly
effective contraceptive methods prevent
unintended pregnancy, maternal/infant
morbidity and mortality, and vertical
transmission of HIV
2

3. + Key questions addressed by WHO:
Do specific methods of hormonal
contraception increase risk of:
1. HIV acquisition in uninfected women?
2. HIV transmission to uninfected male partners?
3. HIV disease progression in women living with
HIV?
3

4. + Do specific methods of hormonal
contraception increase risk of:
1. HIV acquisition in HIV-negative women?
2. HIV transmission to HIV-negative male partners?
3. HIV disease progression in women living with
HIV?
4

5. + 2012 systematic review: Polis & Curtis
 Systematic
search of published literature
 Any
language, any date through Dec 15, 2011
 Included RCT, prospective cohort, or case-control
studies
 Excluded cross-sectional studies
 Studies
compared HIV-uninfected women
using HC vs. HIV-uninfected women not
using HC
5

6. Observational studies of OCs & HIV acquisition
Adjusted OR, IRR, or HR (log scale) and 95% CI
Slide courtesy of C Polis
6

7. Observational studies of injectables & HIV acquisition
Adjusted OR, IRR, or HR (log scale) and 95% CI
Slide courtesy of C Polis
7

8. +
Observed association: Causal or
confounding?

Causal: DMPA use  Increased risk of HIV acquisition

Confounding: DMPA use  Less consistent use of
condoms  Increased risk of HIV acquisition

Other potential factors: Provider bias in prescribing; women
more at risk more likely to use DMPA

With only observational data available impossible to
determine what is truly being measured

Some biological data bolster argument for an
association, but also inconsistent

Does it matter?

9. +
New MEC Recommendation for
women at high risk of HIV
COC/CIC/POP
1
Patch/Ring
1
DMPA/NET-EN
11
Implant
1
See clarification

10. + WHO HC-HIV consultation
technical statement, Feb 2012
…the group agreed that the data were not
sufficiently conclusive to change current guidance…
…However, because of the inconclusive nature of
the evidence, women using progestogen-only
injectable contraception should be strongly advised
to also always wear condoms and other HIV
preventive measures…
Expansion of contraceptive method mix and further
research on the relationship between hormonal
contraception and HIV infection is essential. These
recommendations will be continually reviewed in
light of new evidence.
10

11. + New data since WHO meeting
McCoy et al. analysis of MIRA data

Secondary data analysis of 4913 women in SA and Zimbabwe
participating in HIV prevention study
Site-adjusted
Cox PH
Baselineadjusted
Cox PH
IPTW Cox
PH MSM
Injectables 1.32
(1.00-1.74)
1.27
1.34
(0.94-1.72) (0.75-2.37)
OCs
0.84
0.86
(0.57-1.22) (0.32-1.78)
* AIDS 2013 (in press)
0.82
(0.58-1.15)
11

12. + Competing risks: Hormonal
contraception for women living
with HIV
 Restrictions
on highly effective methods could
increase unintended pregnancies, if not replaced
by other highly effective methods
 Unintended
pregnancy has implications on
maternal and infant morbidity/mortality, perinatal
HIV, possibly on response to ART, and on overall
wellbeing
 Pregnancy
itself may impact risk of HIV
transmission, additional evidence needed
12

13. + Do specific methods of hormonal
contraception increase risk of:
1. HIV acquisition in uninfected women?
2. HIV transmission to HIV-negative male partners?
3. HIV disease progression in women living with
HIV?
13

14. +
2012 systematic review: Polis, Phillips, &
Curtis*
Study selection
 Systematic


literature search
Any language, any date through Dec 15, 2011
Studies compared HIV-infected women using HC to HIVinfected women not using HC
 Direct
evidence: outcome = incident
seroconversion in male partner of woman with
known HC use status
 Indirect
evidence: outcome = genital HIV shedding
or plasma viral load
* AIDS 2013; 27:(493-505)
14

15. + Direct evidence: 1 study identified
(Heffron 2012*)

2476 couples with HIV-infected women

59 genetically-linked seroconversions in men


15 to men with partners using injectables


40 to men with partners not using HC (1.51/100 py)
4 to men with partners using OCs
(2.64/100 py)
(2.50/100 py)
Partners of HC users twice as likely to seroconvert

adjHR OCs:
2.1 (0.8-5.8)

adjHR injectables: 2.0 (1.1-3.6)
* Lancet Infectious Diseases 2012;12(1):19-26
15

16. + Indirect evidence from 17 studies
 Genital
HIV shedding: assessment techniques,
outcomes, & findings from 11 reports inconsistent
 Plasma
viral load: generally consistent evidence of no
association from nine reports
16

17. + Summary of transmission results
 One
well-conducted study raises potential concerns
related to the use of injectable contraception and
transmission
 Given
the paucity of direct evidence, mixed indirect
evidence from 16 studies, and the potential for
confounding, additional evidence is needed
17

18. + Do specific methods of hormonal
contraception increase risk of:
1. HIV acquisition in HIV-negative women?
2. HIV transmission to HIV-negative male partners?
3. HIV disease progression in women living with
HIV?
18

19. +
Voluntary contraception: Crucial
care for women living with HIV
 Women
living with HIV who wish to have children
should be supported
 Women
living with HIV who wish to defer or stop
childbearing must similarly be supported

Critical to their health and to preventing vertical HIV
transmission
 Hormonal
contraception highly effective and
acceptable to women

20. + 2012 systematic review:
Phillips, Curtis, & Polis*
 Systematic
literature search; any language, any date
through Dec 15, 2011
 12
reports included (1 RCT, reported twice; 11
observational)
 Excluded: studies
with no comparison group; case
control studies
 HIV
disease progression measured by mortality,
time to CD4 count below 200, time to ART initiation,
increase in HIV RNA viral load, or decrease in CD4
cell count
* AIDS 2013 27(5): 787–794
20

21. +
Studies assessing OCs and mortality
(Adj HR)
Stringer RCT (2009)*
Kilmarx (2000)
MRC (1999)
Polis (2010)
Allen (2007)
OCs decrease
risk of mortality
OCs increase risk
of mortality
*Actual use analysis
21

22. +
Studies assessing injectables and
mortality (Adj HR)
Stringer RCT (2009)*
Kilmarx (2000)
Polis (2010)
Stringer Multi-Country (2009)
Allen (2007)
Injectables decrease
risk of mortality
Injectables increase
risk of mortality
*Actual use analysis
22

23. +
Summary of HIV disease
progression results
 One
randomized trial raised some concerns; had
important limitations related to crossover and
dropout
 Ten
observational studies reported no increased
risk for HIV disease progression

24. +
New MEC Recommendation for
women living with HIV (unchanged
from prior recommendations)
COC/CIC/POP
1
Patch/Ring
1
DMPA/NET-EN
1
Implant
1
Women on ART may require special consideration
regarding the use of hormonal contraceptives

25. + New since 2012 WHO meeting:
Heffron 2013*
 2269
women living with HIV
 HC
does not accelerate disease progression and may be
associated with slower progression
Contraception Adjusted HR
(95% CI)
No HC
Any HC
p-value
Reference
0.74 (0.56-0.98) 0.04
Injectables
0.72 (0.53-0.98) 0.04
OCPs
0.83 (0.48-1.44) 0.50
* AIDS 2013; 27(2): 261-267
25

26. + Conclusions: Safety of hormonal
contraception for women living with HIV

HIV disease progression: neither OCPs nor DMPA appear to
accelerate HIV disease progression

Transmission to HIV-negative male partners: evidence base
limited, inconsistent

One direct study suggests increase risk with HC

Indirect evidence on HC and shedding is inconsistent, on HC and
plasma viral load suggests no increase in risk

Consider findings in context of increasing use of ART

Importance of counseling on HC plus HIV prevention interventions
26

27. + Conclusions: Safety of hormonal
contraception for HIV-negative women at
risk for HIV acquisition

OCPs: data do not suggest an increased risk of HIV acquisition

Implants, rings, patches, hormonal IUDs: limited data

NET-EN: data are limited, do not suggest increased risk

DMPA: substantial uncertainty

Potential risk must be balanced against risks of unintended pregnancy
(maternal morbidity & mortality, unsafe abortion, infant morbidity
&mortality), and potential risk of HIV acquisition associated with
pregnancy
27

28. +
Thank you!

Acknowledgments:

Chelsea Polis, PhD

Kathryn Curtis, PhD

Mary Lyn Gaffield, PhD

Further information at:
http://www.who.int/reproductivehealth/topics/family_planni
ng/hc_hiv/en/

Contact: phillipss@who.int

29. + HC for women using ARVs
Type of ARV
Nucleoside
reverse
transcriptase
inhibitors
(NRTIs)
Hormonal methods of
contraception
COC, CIC,
DMPA, NET-EN,
P/R, POP
LNG/ETG
Category 1
Category 1
Intrauterine contraception
(either Cu-IUD or LNG-IUD)
Initiation
Continuation
Category 2/3*
Category 2
Category 2
DMPA: Category 1 Category 2/3*
NET-EN,
LNG/ETG:
Category 2
Category 2
RitonavirCategory 3
boosted protease
inhibitors
DMPA: Category 1 Category 2/3*
NET-EN,
LNG/ETG:
Category 2
Category 2
Non-nucleoside
reverse
transcriptase
inhibitors
(NNRTIs)
* There is no known interaction between ART & IUD use. However, AIDS as a condition is classified as
Category 3 for insertion and Category 2 for continuation unless the woman is clinically well on
antiretroviral therapy, in which case both insertion and continuation are classified as Category 2
29

30. Method mix: among all married users,
percent using specific method
Source: UNPD 2011