Contraception for HIV-infected Women and Couples (PowerPoint)

Contraception for HIV-infected Women and Couples Deborah Cohan, MD, MPH Assistant 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) – – – HIV and Female Fertility (3)   Possible of  fertility PID/tubal factor (etiologies STDs) – Menstrual disorders (Harlow, et al, 2000)  Polymenorrhea (< 18d cycle) OR 1.45 (1.0-2.11) HIV and Female Fertility (4)  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? HIV and Male Fertility  250 HIV+, 38 HIV-fertile men; cross-sectional – HIV+:  vol.,  concentrat.,  motility,  nl morphol. No difference in count, wbc No AZT, cd4 > 200 = nl semen analysis No AZT, cd4 < 200 = abnl SA AZT: nl SA and  wbc regardless of CD4 Muller 1998; Politch 1994 –  166 HIV+; cross-sectional – – – 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 Intended (51%) Unintended (49%) Unintended Births (22.5%) Elective Abortions (26.5%) Henshaw: Fam Plann Perspect 1998;30:24-29. 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  Reproductive Decision-Making (3)  Not pregnant at/since HIV diagnosis – No desire for future preg: (n=27) MTCT risk usually overestimated, guilt, risk of meds opinions of HIV+ women becoming pregnant Negative Kirshenbaum 2004 Reproductive Decision-Making (4) 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 Kirshenbaum 2004 Reproductive Decision-Making (5)   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? Timing of future pregnancies; permanent vs. reversible  Fertility desires –  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) Withdrawal/Rhythm Diaphragm Condom Pill 0.5% Copper IUD 0.8% Tubal Ligation Injectable Progestin Implants Vasectomy Typical Lowest Expected 0.5% 0.2% 0.1% 0.02% 5% 10% 15% 20% 3% 6% 14% 9% 20% 19% 0% Hatcher: Contraceptive Technology 16th Edition 1994. Pros and Cons of Contraception Options Method Condoms Pros STI/HIV protection Cons requires partner cooper and correct technique OCPs Patch, ring, combo injectable DMPA effective, less blood loss effective, less blood loss low maintenance, effective Rx-Rx interaxns;  shedding? Rx-Rx interaxns?;  shedding?  shedding?,  viral set-point Pros and Cons of Contraception Options (2) Method IUD Pros low maintenance, effective some STI protection Cons blood loss with Copper T, shedding with LNG-IUS?  UTI with diaphragm, requires correct technique no future fertility Cervical barrier Sterilization low maintenance, effective 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) Lindsay Ob Gyn 1995; Wilson JAIDS 2003; Wilson STD 2003  Issues for HIV+ women choosing hormonal methods… 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%) Mildvan JAIDS 2002; http://hivinsite.ucsf.edu; USPHSTF, 3/23/04; Frohlich Br J Cl Phar 2004 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? – – Mildvan JAIDS 2002; http://hivinsite.ucsf.edu; USPHSTF, 3/23/04; Frohlich Br J Cl Phar 2004 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 – Mildvan JAIDS 2002; http://hivinsite.ucsf.edu; USPHSTF, 3/23/04; Frohlich Br J Cl Phar 2004 Hormonal Contraception and Other Drug-drug Interactions  Increased hormone metabolism: – – – – – Rifampin, rifabutin Griseofulvin, toglizatone Phenobarbital, carbamazepine, phenytoin Primidone, topiramate St. John’s Wort 50 mcg EE pill? Extended/continuous cycle?  Clinical implications – 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 Lavreys, JID 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) Mostad Lancet 1997; Marx 1996; Wang AIDS 2004 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 Mostad Lancet 1997; Marx 1996; Wang AIDS 2004 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 Mostad Lancet 1997; Marx 1996; Wang AIDS 2004 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) Wilson, WIHS 561 HIV-, 2040 HIV+  Consistent condom use – – 57% if condoms+ 2nd contracep. vs. 67% if condom use Diaz 1995 Contraception, Condom Use and Partner Status (3)  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 HIVneg. partner and IUD use: OR 2.1 if HIV+ partner  OCP Contraception, Condom Use and Partner Status (4) – 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 Should use within 7 days of unprotected sex Expensive but great long-term contraception  Copper IUD – – 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  Not Required   Pregnancy test (only if could be pregnant by history) Brief review of contraindications (history of DVT/PE if giving estrogencontaining EC) Counseling 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 ProgesteroneOnly EC • Plan B™ vs. Ovral – – No ® or Preven™: Less nausea (23% vs. 50%) Less vomiting (5.6% vs.18.8%) 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 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? Morrison BJOG 2001; Sinei Lancet 1998; Richardson AIDS 1999  Issues for HIV-negative women with HIV+ male partners 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) POP use OR 0.8 (0.6-0.98) (Kenya, n=5301) Kapiga AIDS 1998; Criniti AIDS 2003; Lavreys AIDS 2004 –  Progesterone-only pills:  prevalent HIV – 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? Kapiga AIDS 1998; Criniti AIDS 2003; Lavreys AIDS 2004 Condoms and HIV Acquisition Risk of HIV acquisition in setting of condom use protective not Ahmed 2001; Weller 2004; Davis 1999; Pinkerton 1997; Holmes, Bull WHO, 2004 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 What additional questions? Best options? Case #3  35 yo G2P2 HIV-neg woman and 38 yo HIV+ male partner Considering future pregnancy What additional questions? Best options?    Case #4  26 yo HIV+ G3P1 post-partum with HIV-neg male partner Partner doesn’t like to use condoms What additional questions? Strategies to encourage condom use? Best options?    