Welcome to I-TECH HIV/AIDS
Clinical Seminar Series
3rd June 2010
Contraception in the Setting of HIV
R. Scott McClelland, MD, MPH
Outline
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Brief ‘world view’ of contraception and HIV
What are the benefits of contraception?
Contraception in the setting of HIV
Clinical case studies in contraception
– Safety
– Efficacy
– Side effects
– Management in different clinical scenarios
Learning Objectives
• Be able to provide HIV-positive women with
a clear explanation of the potential benefits
and risks of different contraceptive choices
• Feel comfortable with basic clinical decision
making for initiation and continuation of
contraception in HIV-positive women
Global Use of Contraception
• ~800 million women use
modern methods of
contraception
– ~150 million use
hormonal contraceptives
– Others use intra-uterine
contraceptive devices,
barriers, and tubal ligation
Unmet Contraceptive Need
Ref: Network Vol 23, number 3,
2004. Family Health International
Benefits of Contraception in the
Setting of HIV
• Contraception reduces pregnancy and may
provide additional health, social, and
economic benefits.
– Groups should discuss briefly, then rank top
three benefits of contraception. Consider both
general benefits and specific advantages of
contraception in the setting of HIV.
Benefits of Contraception
• Avoid unplanned pregnancies
– Potential for obstetrical complications
– Spacing pregnancies benefits the health of
women, infants, and children
• Family planning empowers women,
reducing gender inequality
• HIV-positive women may wish to reduce risk
of vertical transmission by preventing further
pregnancies
Case 1
• 24 y.o. HIV+ woman
presents for 6 week postpartum visit. She initiated
ART during pregnancy with
CD4=226. She would like
to avoid another pregnancy.
– Can she be offered hormonal
contraception?
Many Women Living with HIV
Remain Sexually Active
• Abstinence eliminates
sexual transmission
risk, but often not
possible or desired by
women or partners
• Dual protection
minimizes HIV/STI
transmission risk and
lowers risk of
pregnancy
Case 1
• 24 y.o. HIV+ woman
presents for 6 week postpartum visit. She initiated
ART during pregnancy with
CD4=226. She would like
to avoid another pregnancy.
– Will contraception influence
the risk of HIV progression?
Hormonal Contraception and
HIV Progression
• Secondary analysis from 1 RCT suggests
increased disease progression with HC
compared to intrauterine device (IUD)1
• 7 prospective cohort studies suggest HC in
chronic HIV doesn’t significantly change
CD4, plasma viral load, or mortality2,3
1. Stringer et al. AIDS 2009; 23: 1377-82
2. Curtis et al. AIDS 2009; 23 Supplement 1:S55-S67
3. Polis et al. CROI 2010, San Francisco, Feb 2010, abstract 152
Hormonal Contraception vs. IUD
in HIV+ Women
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599 postpartum women in Lusaka, Zambia
RCT IUD vs. hormonal contraception
Followed for at least 2 years
Primary endpoint: Safety and efficacy of
intrauterine device vs. hormonal contraception
• Secondary endpoints:
– Time to CD4<200
– Time to death
– Combined endpoint including either time to CD4<200 or
death
Stringer AJOG 2007:197:144.e1-144.e8
Hormonal Contraception vs. IUD
in HIV+ Women
• Only one episode of PID in IUD arm
• Higher rate of discontinuation in IUD arm
• Pregnancy higher in HC vs. IUD
– HR 2.2 (95% CI 1.2-2.4)
• Mortality did not differ significantly
– HR 1.4 (95% CI 0.7-3.0)
• Faster progression to CD4<200 with
hormonal contraception compared to IUD
– HR 1.6 (95% CI 1.04-2.03)
Hormonal Contraception vs. IUD
in HIV+ Women
CD4 decline
Death
Hormonal Contraception vs. IUD
in HIV+ Women
CD4 decline
Death
CD4 decline
or
death
•Time to CD4<200 or death
faster in HC vs. IUD
• HR 1.6 (95% CI 1.1-2.3)
Study Summary: Hormonal
Contraception vs. IUD in HIV+ Women
• IUD appeared safe and was more
effective than HC at preventing pregnancy
• No difference in mortality
• Time to CD4<200 longer with IUD vs. HC
• Limitations
– ~30% withdrew or lost to follow-up
– ~30% discontinued allocated method
– Postnatal population; can we generalize to
other women?
Hormonal Contraception in
HIV+ Women
• 319 post-partum women in Nairobi1
– No effect on CD4 or plasma VL to 24 months
in Depo-Provera or OCP compared to no HC
• US Women’s Interagency HIV Study2
– Plasma VL not influenced by HC
– Small increase in CD4 over long-term follow-up
• 213 women initiating HC in Mombasa3
– No increase in plasma VL over 2 months
1. Richardson AIDS 2007; 21:749-53
2. Cejtin AIDS 2003;17:1702-4
3. Wang AIDS 2004;18:205-9
Hormonal Contraception and Time
to AIDS or Death: Rakai, Uganda
• 625 women followed from HIV acquisition
• Use of HC associated with lower risk of
AIDS/death aHR (0.70, 95%CI 0.50-0.97)
– Effect appeared to be present only after median
time to AIDS/death (4.4 years)
– Compared to women using non-hormonal
contraception, HC users had similar risk of
progression
Polis et al. CROI 2010, San Francisco, Feb 2010, Abstract 152
Hormonal Contraception and
HIV Progression
• Majority of evidence (from cohort studies)
suggests that initiating HC in HIV+ women
does not increase disease progression
– One RCT suggested increased progression, but
with several important limitations
Case 2
• 27 y.o. woman reports sex
work and has been screened
periodically for HIV with
multiple prior negative tests.
Uses Depo-Provera to
prevent pregnancy. She now
has a positive HIV test.
– Will Depo-Provera use at the
time of HIV acquisition
influence the natural history of
her HIV infection?
http://www.street-papers.org/eastern-asia/
Hormonal Contraception and
HIV Progression
• Effect may differ depending on the timing of
hormonal contraception in relation to HIV-1
acquisition
– Hormonal contraception initiation during chronic
HIV infection (e.g. Case 1)
– Hormonal contraception at the time of HIV
acquisition (e.g. Case 2)
Depo-Provera at Time of
HIV Acquisition
• Indirect evidence from
surrogate endpoints
– Women using DMPA at the time
of HIV acquisition have
• Higher set-point plasma viral load
• Greater viral diversity at infection
• Viral diversity is associated with
more rapid CD4 decline
Sagar et al. J Virol 2003; 77:12921-12926
Sagar M et al. AIDS 2004;18:615-619.
Hormonal Contraception and
HIV Progression
• Majority of evidence (from cohort studies)
suggests that initiating HC in HIV+ women
does not increase disease progression
– One RCT suggested increased progression, but
with several important limitations
• HC at time of infection may influence
diversity of the infecting viral population, set
point VL, and rate of CD4 decline
– Unknown effect on morbidity and mortality
Case 3
• 30 y.o. HIV+ woman with CD4=440 desires
oral contraceptive pills (OCPs) to prevent
pregnancy. Which of the following does
WHO recommend prior to initiating OCPs?
– A) Medical History and blood pressure
– B) Pap Smear
– C) Breast examination
– D) STI screening
– E) All of the above
Case 3
• 30 y.o. HIV+ woman with CD4=440 desires
oral contraceptive pills (OCPs) to prevent
pregnancy. Which of the following does
WHO recommend prior to initiating OCPs?
– A) Medical History and blood pressure
– B) Pap Smear
– C) Breast examination
– D) STI screening
– E) All of the above
Screening prior to Hormonal
Contraceptive Initiation
• Careful medical history and
BP are recommended.
– Other elements of health
screening advisable, but not
required for initiation of
hormonal contraception
Screening prior to Hormonal
Contraceptive Initiation
• Which element of medical history and exam
would be a contraindication to OCPs?
– A) Smokes regularly, ~20 cigarettes/day
– B) History of leg blood clot after long bus ride
– C) Current blood pressure 138/88
– D) History of hypertension during pregnancy
with normal blood pressure on present exam
– E) All of the above would be contraindications to
OCPs in this patient
Screening prior to Hormonal
Contraceptive Initiation
• Which element of medical history and exam
would be a contraindication to OCPs?
– A) Smokes regularly, ~20 cigarettes/day
– B) History of leg blood clot after long bus ride
– C) Current blood pressure 138/88
– D) History of hypertension during pregnancy
with normal blood pressure on present exam
– E) All of the above would be contraindications to
OCPs in this patient
Contraindications to OCPs
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Pregnancy
Prior thromboembolic event or stroke
History of estrogen-dependent tumor
Active liver disease
Undiagnosed abnormal uterine bleeding
Hypertriglyceridemia
Age >35 AND smoking >15 cigarettes daily
Age >35 with migraine
Migraine with aura (any age)
Poorly controlled hypertension
Case 3
• 30 y.o. HIV+ woman with CD4=440 starts
OCPs on the first Sunday after her menses.
What is the annual risk of pregnancy with
typical use?
– A) 0.1%
– B) 1.0%
– C) 4%
– D) 8%
– E) 12%
Case 3
• 30 y.o. HIV+ woman with CD4=440 starts
OCPs on the first Sunday after her menses.
What is the annual risk of pregnancy with
typical use?
– A) 0.1%
– B) 1.0%
– C) 4%
– D) 8%
– E) 12%
Pregnancy Rates in First Year
Male Condom
Depo-Provera
IUD
OCP (E/P)
Typical Use
15%
3%
<1%
8%
Contraceptive Technology, 19th Ed. 2007
Correct Use
2%
<1%
<1%
<1%
Case 3
• 30 y.o. HIV+ woman with CD4=440 starting
OCPs (E/P with 30 mcg ethinyl estradiol).
She should be advised to use backup
contraception:
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A) Until next menses if she misses a single dose
B) For 7 days if she misses a single dose
C) For 1 month after missing 3 consecutive doses
D) For 7 days if she misses 3 consecutive doses
E) None of the above
Case 3
• 30 y.o. HIV+ woman with CD4=440 starting
OCPs (E/P with 30 mcg ethinyl estradiol).
She should be advised to use backup
contraception:
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A) Until next menses if she misses a single dose
B) For 7 days if she misses a single dose
C) For 1 month after missing 3 consecutive doses
D) For 7 days if she misses 3 consecutive doses
E) None of the above
Missed Doses
WHO. Family Planning Handbook
Case 4
• 32 y.o. HIV+ woman was
diagnosed with HIV/TB coinfection and CD4=236.
Now on AZT, 3TC, NVP
(month 5) and in her 5th
month of TB treatment
(continuation phase with
INH+Rifampicin). Also
taking daily Septrin. She
asks about family planning.
WHO. Family Planning Handbook
Case 4
• What medications may interact with hormonal
contraceptives?
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A) Rifampicin
B) Isoniazid
C) Nevirapine
D) All of the above
E) A and C
Case 4
• What medications may interact with hormonal
contraceptives?
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A) Rifampicin
B) Isoniazid
C) Nevirapine
D) All of the above
E) A and C
Drug Interactions
• Metabolism of steroid hormones increased
– Rifampicin
– NNRTIs
– Some anticonvulsants
• Metabolism of steroid hormones decreased
– Lopinavir boosted with ritonavir (Kaletra/Aluvia)
Case 4
• Based on potential drug interactions in this patient
taking AZT, 3TC, NVP, INH, Rif, and Septrin,
which contraceptive regimen may be expected to
have benefits generally outweighing risks:
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A) Progesterone-only pills
B) Combined oral contraceptive pills
C) Depot Medroxyprogesterone acetate (Depo-Provera)
D) None of the above, she should use a non-hormonal
method for contraception
Case 4
• Based on potential drug interactions in this patient
taking AZT, 3TC, NVP, INH, Rif, and Septrin,
which contraceptive regimen may be expected to
have benefits generally outweighing risks:
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A) Progesterone-only pills
B) Combined oral contraceptive pills
C) Depot Medroxyprogesterone acetate (Depo-Provera)
D) None of the above, she should use a non-hormonal
method for contraception
Drug Interactions
• There are generally
fewer clinically
significant interactions
with Depo Provera
• Contraceptive efficacy
remains high despite
theoretical interactions
WHO. Family Planning Handbook
Case 4
• 32 y.o. HIV+ woman was with HIV/TB co-infection
and CD4=236. On AZT, 3TC, NVP, INH, Rif, and
Septrin. Initiated Depo-Provera within 5 days of
menses. She was given a follow-up visit for 12
weeks later, but arrived 10 days late for the
scheduled visit. The WHO recommends:
– A) Give her next injection now without pregnancy test
– B) Pregnancy test now; if negative give next injection
– C) Use condoms until next menses, then re-initiate
hormonal contraception
Case 4
• 32 y.o. HIV+ woman was with HIV/TB co-infection
and CD4=236. On AZT, 3TC, NVP, INH, Rif, and
Septrin. Initiated Depo-Provera within 5 days of
menses. She was given a follow-up visit for 12
weeks later, but arrived 10 days late for the
scheduled visit. The WHO recommends:
– A) Give her next injection now without pregnancy test
– B) Pregnancy test now; if negative give next injection
– C) Use condoms until next menses, then re-initiate
hormonal contraception
Late for Depo-Provera?
• WHO 2008 update allows a grace
period of up to 4 weeks without
need for pregnancy testing
• Based on Steiner et. al.
Contraception 2008
– On time 0.6 (95%CI 0.33-0.92)
pregnancy/100 p-y
– 2 weeks 0.0 (95%CI 0.00-1.88)
pregnancy/100 p-y
– 4 weeks 0.4 (95%CI 0.01-2.29)
pregnancy/100 p-y
Case 4
• 32 y.o. HIV+ woman on ART, TB treatment, and
Depo-Provera. Side effects of DMPA include:
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A) Increased risk of endometrial cancer
B) Reduced bone mineral density
C) Increased risk of deep venous thrombosis
D) A and C
E) All of the above
Case 4
• 32 y.o. HIV+ woman on ART, TB treatment, and
Depo-Provera. Side effects of DMPA include:
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A) Increased risk of endometrial cancer
B) Reduced bone mineral density
C) Increased risk of deep venous thrombosis
D) A and C
E) All of the above
Depo-Provera Side Effects
• Menstrual changes
• Weight changes
• Decreased bone mineral density
– BMD decreased by 0.5-3.5% after one year and
by 5.7-7.5% after two years
– Most important in young women who have not
attained peak bone mass and in perimenopausal women
ACOG Committee. Obstet Gynecol 2008; 112:727.
Depo-Provera
Non-Contraceptive Benefits
• Depo-Provera associated with 80% lower
risk of endometrial cancer1
• No increase in risk for ovarian, cervical,
hepatic malignancy
• In contrast to combined OCPs:
– No increased production of coagulation factors
– No increase in DVT, stroke, or MI
– No adverse effects on blood pressure
Case 5
• 37 year old woman presents to clinic for
initial evaluation for HIV. CD4=177. No
history of significant illness. She had a
Copper T IUD inserted 3 years ago. What is
recommended for her contraception?
– A) Leave the IUD in place
– B) Remove IUD and recommend Depo-Provera
– C) Remove IUD and recommend barrier method
until she is on ART at least 6 months
Case 5
• 37 year old woman presents to clinic for
initial evaluation for HIV. CD4=177. No
history of significant illness. She had a
Copper T IUD inserted 3 years ago. What is
recommended for her contraception?
– A) Leave the IUD in place
– B) Remove IUD and recommend Depo-Provera
– C) Remove IUD and recommend barrier method
until she is on ART at least 6 months
IUD for Women with HIV
• Women with HIV or with AIDS but on ART
and clinically well can have IUD inserted
• Women with AIDS, not on ART or not
clinically well should not have IUD inserted
• If a woman develops AIDS and has IUD in
place, it does not have to be removed
Summary
• Contraceptive services important
for comprehensive HIV care
• Initiating contraception does not
increase HIV progression
• Contraception similar in HIV+ and
HIV- women
– Encourage dual method use
including a barrier method
– Consider drug interactions
Thank you!
Next session: June 17th
Nina Kim, OIs
Email: DLinfo@u.washington.edu