Contraception for HIV-infected Women and Couples Deborah Cohan, MD, MPH Assistant Clinical Professor Department of Ob/Gyn, UCSF.

Contraception for HIV-infected Women and Couples

Deborah Cohan, MD, MPHAssistant Clinical Professor

Department of Ob/Gyn, UCSF

Overview

HIV and fertility Reproductive decision-making Contraceptive counseling Contraceptive methods

– Hormonal contraception– Condoms – Emergency contraception (EC)– Intrauterine devices

Contraception and HIV

What Won’t Be Covered

Microbicides

Cervical barriers and HIV acquisition

Resource-limited settings

HIV and Female Fertility

Decreased fertility???

– Uganda: fertility by 25% (Ross, et al, 1999)

– Cote d’Ivoire: fertility by 17% (Desgrees, et al, 1999)

0.4% fertility rate per % HIV preval in ♀ population (Zaba, et al, 1998)

HIV and Female Fertility (2)

Increased miscarriages/stillbirths???

– Cote d’Ivoire: OR 1.28 (1.02-1.60) (Desgrees et al, 1998)

– Uganda: OR 1.50 (1.01-2.27) (Gray, et al, 1998)

– Italy: OR 1.67 (D’Ubaldo, et al, 1998)

– U.S.: no difference (Forsyth, AIDS 2002)


Possible of fertility

PID/tubal factor (etiologies STDs)

– Menstrual disorders (Harlow, et al, 2000)

Polymenorrhea (< 18d cycle) OR 1.45 (1.0-2.11)


Oligomenorrhea (> 90d cycle) OR 1.32 (0.68-2.58)

a) especially high viral loads, low CD4 counts

b) OR 7.1 (1.1-1000) (Chirgwin, et al, 1996)

– Opiates, testosterone, malnutrition ( BMI)

– Direct effects of HIV on uterus, tubes, ovaries? ART improves fertility?

Muller 1998; Politch 1994

HIV and Male Fertility

250 HIV+, 38 HIV-fertile men; cross-sectional

– HIV+: vol., concentrat., motility, nl morphol.

– No difference in count, wbc 166 HIV+; cross-sectional

– No AZT, cd4 > 200 = nl semen analysis

– No AZT, cd4 < 200 = abnl SA

– AZT: nl SA and wbc regardless of CD4

HIV and Male Fertility (2)

Regardless of possible risk of sub-fertility or infertility, HIV+ women and partners of HIV+ men get pregnant….

Unintended Pregnancy in U.S.

50% of all pregnancies are unintended

1/2 of these are in women USING CONTRACEPTION

Immense personal and societal implications and costs

U.S. Pregnancies: Unintended vs. Intended

Henshaw: Fam Plann Perspect 1998;30:24-29.

Unintended (49%)

Intended (51%)

Unintended Births (22.5%)

Elective Abortions (26.5%)

Pregnancy Scenarios

Planned pregnancy– WIHS: 2040 HIV+, 561 HIV-neg– 3.5% HIV+ vs. 9% HIV- (p < 0.01) (Wilson,

et al, 1999)

Pregnancy Scenarios (2)

Unintended pregnancy

– Termination (TAb) of pregnancy

TAb: 28% (Italy), 47% (2x national average, Australia), 58% (Sweden) (Smits, 1999; Greco, 1999; Thackway, 1997, Lindgren, 1998)

Pregnancy Scenarios (3)

TAb’s if HIV dx after pregnancy dx

a) 10.6/100 PY vs. 3.1/100 PY (p=0.001) (Hankins, et al, 1999)

TAb’s after March 1994 (Europe; van Benthem 2000)

a) 4.3/100 PY vs. 1.4/100 PY after 3/94

Reproductive Decision-Making

Perception of HIV risk

Knowledge of risk reduction methods

Clinical course of HIV

Adaptation to HIV status of self/partner

Disclosure of HIV status

Reproductive Decision-Making (2)

Health concerns for self, couple, offspring

Desire to parent

Influence of partner, family, culture, peers, providers

Availability of contraception, abortion services

Kirshenbaum 2004


Not pregnant at/since HIV diagnosis

– No desire for future preg: (n=27)

MTCT risk usually overestimated, guilt, risk of meds

Negative opinions of HIV+ women becoming pregnant

Kirshenbaum 2004


YET…strong desire for motherhood, pressure from partners

– Desire for future preg: (n=5), 4/5 w/o prior pregnancies

undetectable viral load, ART and c-section to prevent transmission


Pregnant after HIV diagnosis (n=3)– Less trusting of risk-reduction strategies than 5

desiring preg. Pregnant at HIV diagnosis (n=12), all had term preg.

– 50% not wanting subsequent pregnancies“lucky” this time, overestimated MTCT risk,

many tubal ligation– Subsequent preg: desire to correct past parenting

mistakes

How to counsel those not wanting to conceive…

Contraceptive Counseling:General Principles Establishing need

Contraception history

– What worked and didn’t? Side-effects tolerable/intolerable?

Fertility desires

– Timing of future pregnancies; permanent vs. reversible

Hormonal vs. non-hormonal

Contraceptive Counseling:General Principles (2)

Non-contraceptive benefits (co-existing med. probs.)

Beliefs about contraceptive options

Sexual history and relationship dynamics

Concordance/discordance of HIV-status

Contraception Failure (1st Year)

Hatcher: Contraceptive Technology 16th Edition 1994.

14%

20%

0.1%

0.2%

0.5%

0.5%

9%

6%

3%

19%

0.02%

0.8%

0% 5% 10% 15% 20%

Vasectomy

Implants

Injectable Progestin

Tubal Ligation

Copper IUD

Pill

Condom

Diaphragm

Withdrawal/Rhythm

Typical

Lowest Expected

Pros and Cons of Contraception Options

Method Pros Cons

Condoms STI/HIV protection requires partner cooper and correct technique

OCPs effective, less blood loss

Rx-Rx interaxns; shedding?

Patch, ring, combo injectable

effective, less blood loss

Rx-Rx interaxns?; shedding?

DMPA low maintenance, effective

shedding?, viral set-point

Pros and Cons of Contraception Options (2)

Method Pros ConsIUD low maintenance,

effectiveblood loss with Copper T, shedding with LNG-IUS?

Cervical barrier some STI protection UTI with diaphragm, requires correct technique

Sterilization low maintenance, effective

no future fertility

Lindsay Ob Gyn 1995; Wilson JAIDS 2003; Wilson STD 2003

Contraceptive Choices and HIV

Post-partum

83 HIV+, 218 HIV-neg (1995)

– PPTL: OR 2.9 (1.4-5.9)

– OCP: OR 0.2 (0.1-0.5); condoms: 0.7 (0.4-1.3)

Lindsay Ob Gyn 1995; Wilson JAIDS 2003; Wilson STD 2003

Contraceptive Choices and HIV (2)

258 HIV+, 228 HIV-neg. (1996-98)

– Condoms at 6 mos.: OR 5.61 (3.42-9.22)

– Consistent condom use: OR 2.31 (1.35-3.94)

– OCP: OR 0.54 (0.30-0.98)

– No method: OR 0.30 (0.14-0.65)

179 HIV+, 182 HIV-neg.

– Dual protection at 6 mos.: OR 2.75 (1.16-6.50)

Issues for HIV+ women choosing hormonal methods…

Mildvan JAIDS 2002; http://hivinsite.ucsf.edu; USPHSTF, 3/23/04; Frohlich Br J Cl Phar 2004

OCPs and ART Interactions

Increased levels of estradiol (EE)/norethindrone (NE)

– APV ( NE/EE), ATV ( NE 110%, EE 48%), IDV ( NE 26%, EE 24%)

– EFV ( EE 37%)


OCPs and ART Interactions (2)

Decreased levels of EE/NE

– NFV ( NE 18%, EE 47%), RTV ( EE 40%), LOP ( EE 42%)

– NVP ( EE 20%)

– Clinical implications? 50mcg EE pill? Extended/continuous cycle?


OCPs and ART Interactions (3)

Decreased levels of ART with concurrent EE/NE

– Amprenavir (1200mg): APV AUC 22%, Cmin 20%

– No change in saquinavir (HGC) pK parameters

Hormonal Contraception and Other Drug-drug Interactions

Increased hormone metabolism:

– Rifampin, rifabutin

– Griseofulvin, toglizatone

– Phenobarbital, carbamazepine, phenytoin

– Primidone, topiramate

– St. John’s Wort

Clinical implications

– 50 mcg EE pill? Extended/continuous cycle?

Lavreys, JID 2004

DMPA and Viral Set-Point

161 Kenyan sex workers with acute infection

DMPA assoc. viral load @ 4 mos. after infxn.

– HIV-1 RNA + 0.33 log/copies

No association seen with OCPs

GUD assoc. HIV-1 RNA + 0.029 log/copies/month but no viral set-point

Mostad Lancet 1997; Marx 1996; Wang AIDS 2004

Hormonal Contraception and HIV shedding

OCPs

cervical proviral shedding; cross-sectional, n=318, Kenya

Low-dose OCPs OR 3.8 (1.4-9.9)

High-dose OCPs (50mcg E2) OR 12.3 (1.5-101)


Hormonal Contraception and HIV shedding (2) Progesterone

cervical proviral shedding (Mostad, et al, 1997) DMPA OR 2.9 (CI 1.5-5.7)

– Macaque data: subQ progesterone implants (Marx, et al, 1996) Thinned the vaginal epithelium and SIV

vaginal transmission 7.7-fold # SIV DNA-positive cells in the

vaginal lamina propria


Hormonal Contraception and HIV shedding (3)

DMPA, OCP, POP initiation; longitudinal cohort

cervical DNA shedding OR 1.62 (1.0-2.63), no change RNA

Diaz 1995

Contraception, Condom Use and Partner Status

n=1232 HIV+ women in US, 12 cities/states

47% women used condoms in past year

No condom use associated with

– Tubal ligation OR 1.72 (1.28-2.33)

– OCP’s OR 1.44 (1.0-2.08)

– HIV+ steady partner OR 1.40 (1.04-1.87)

– Steady partner with unknown status OR 1.72 (1.28-2.31)

Diaz 1995

Contraception, Condom Use and Partner Status (2)

No condom use INVERSELY associated with

– Foam OR 0.01 (0.00-0.09)

– Cervical barrier OR 0.36 (0.14-0.90)

– Rhythm or w/d OR 0.18 (0.06-0.54)

Consistent condom use

– Wilson, WIHS 561 HIV-, 2040 HIV+

– 57% if condoms+ 2nd contracep. vs. 67% if condom use


Contraceptive use and partner status

– n=575 HIV+ women (429 HIV-neg. partner)

– Partner status: 91% contra use if HIV-neg. vs. 69% if HIV+

Consistent condom use: OR 6.1 if HIV-neg. partner

OCP and IUD use: OR 2.1 if HIV+ partner


– EC use assoc with inconsistent condoms: OR 2.0 if partner HIV-neg. or HIV+

age 40-49 yr old: OR 0.3 if HIV+ partner

Emergency Contraception

Prevents pregnancy after unprotected sex

“Morning-after” pill, post-coital contraception, Yuzpe method, Preven™, Plan B™

Could prevent 1.7 million unintended pregnancies and reduce abortions by 50%

1-888-not-2-late

EC Use

Should use within 120 hours of unprotected sex 2 doses total: 2 at same time vs. 1 dose q12 hrs. Dose

– 1 Plan B™ tabs (0.75 mg LNG)– 2 Preven™ tabs (0.25 mg LNG + 0.05 mg EE)– 4-5 combo OCPs – 20 POPs, such as Ovrette™ (0.075 LNG)

OTC anti-emetic if OCP’s or Preven™ 1 hr. prior

EC: Other Options

RU 486

– Most effective (100%)

– Fewest side effects

– Expensive, not available

Copper IUD

– Should use within 7 days of unprotected sex

– Expensive but great long-term contraception

ECP: Mechanism

Will NOT interrupt an established pregnancy

– Ineffective but not harmful if already pregnant

Interferes with implantation via effects on endometrium and/or tubal motility

Inhibits ovulation when given in 1st half of cycle

When is EC needed?

Condom breaks or slips off

No birth control is used, including rape

2 or more consecutive OCPs are missed

Depo-Provera injection 2 or more weeks late

ECP: Pre-Rx Screening

Required Pregnancy test (only if

could be pregnant by history)

Brief review of contraindications (history of DVT/PE if giving estrogen-containing EC)

Counseling

Not Required

Office visit

Routine pregnancy test

Prescription in some states!!!

EC: Counseling

Efficacy

– Prevents 75-88% of pregnancies that would have occurred

– Approx. 2% of those who use will become pregnant

Side effects: 50% nausea, 20% vomit (with estrogen- containing pills, much lower with progestin only)

– Repeat dose if vomits < 1 hour after taking

EC: Counseling (2)

Safety: very safe. No long-term effects Pre-existing pregnancy: will not be terminated

by this method but will not be harmed either Effective birth control methods

– Review future contraceptive plans STI exposure? Next period should be < 3 weeks

– If no period, pregnancy test

Advantages of Progesterone-Only EC

• Plan B™ vs. Ovral® or Preven™:

– Less nausea (23% vs. 50%)

– Less vomiting (5.6% vs.18.8%)

No anti-emetic necessary

Rare replacement doses because less vomiting

– More effective (88% vs. 75%)

Advance Provision of EC

THE SOONER THE BETTER

• Some effect up to 5 days

• Some effect if one dose only

• Over-the-counter in Alaska, California, Hawaii, Maine, New Mexico, Washington and Europe

Morrison BJOG 2001; Sinei Lancet 1998; Richardson AIDS 1999

Intrauterine Device and HIV

156 HIV+, 493 HIV- Kenya cohort; Copper IUD

– Overall complications: HR @ 24 mos. 1.0 (0.6-1.6)

– PID: 2% for HIV+ vs. 0.4% for HIV- (p=0.09)

– Any infection: 10.7% HIV+ vs. 8.8% HIV-; OR 1.02 (0.46-2.27)

Morrison BJOG 2001; Sinei Lancet 1998; Richardson AIDS 1999

Intrauterine Device and HIV (2)

No evidence of HIV shedding with IUD

– n=98, Kenya

– 4 months s/p insertion: shedding OR 0.6 (0.3-1.1)

effectiveness if severe immunosuppression?

LNG-IUS: effectiveness? shedding? PID risk lower?

Issues for HIV-negative women with HIV+ male partners

Kapiga AIDS 1998; Criniti AIDS 2003; Lavreys AIDS 2004

Contraception and HIV Acquisition

No association

– OCP RR 1.01 (0.4-2.3); DMPA RR 0.3 (0.1-1.3), IUD 0.8 (0.4-1.7) (Tanzania, n=2471)

– OCP IRR 1.12 (0.48-2.56); DMPA IRR 0.84 (0.41-1.72) (Uganda, n=5117)

Progesterone-only pills: prevalent HIV

– POP use OR 0.8 (0.6-0.98) (Kenya, n=5301)

Kapiga AIDS 1998; Criniti AIDS 2003; Lavreys AIDS 2004

Contraception and HIV Acquisition (2)

DMPA

– HR 1.8 (1.4-2.4) (Kenya, n=1498)

OCPs

– HR 1.5 (1.0-2.1)

Cervical barriers (diaphragm, cap, etc.): protective?

Ahmed 2001; Weller 2004; Davis 1999; Pinkerton 1997; Holmes, Bull WHO, 2004

Condoms and HIV Acquisition

Risk of HIV acquisition in setting of condom use protective not

Case #1

32 yo HIV+ G5P3 with new HIV+ partner

CD4=345, viral load < 75

Taking combivir, kaletra

Children in foster care

What additional questions?

Best options?

Case #2

25 yo HIV+ G0, newly diagnosed

CD4=55, viral load 65,300

Just started on combivir, efavirenz

Didn’t like taking birth control pills in past


Best options?

Case #3

35 yo G2P2 HIV-neg woman and 38 yo HIV+ male partner

Considering future pregnancy


Best options?

Case #4

26 yo HIV+ G3P1 post-partum with HIV-neg male partner

Partner doesn’t like to use condoms


Strategies to encourage condom use?

Best options?

Contraception for HIV-infected Women and Couples Deborah Cohan, MD, MPH Assistant Clinical Professor Department of Ob/Gyn, UCSF.

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