Jean Anderson, MD Catherine Sewell, MD, MPH

Transcription

1 Jean Anderson, MD Catherine Sewell, MD, MPH

2

3 No Relevant Financial Relationships with Commercial Interests

4 To review contraception in the setting of HIV infection and address controversies

5 33 yo P5015, presented for routine gyn care in 7/2011 HIV diagnosed in 2008, on HAART, CD4 652, VL<50 Condoms only for contraception and STD prevention; uses only 70% of time declines additional methods despite counseling

6 WIHS: ( ), n=2784; 26,832 visits ( J Women s Health 2007, 16:857) Barrier methods: % of visits Tubal ligation: % Hormonal method: <10% of visits No contraception: >30% HIV+ less likely to use hormonal method Italy: 334 women on ART at time of conception 57.6% unplanned pregnancies ( Floridia M et al. Antivir Ther 2006;11: ) HIV+ pregnant US adolescents (n = 1090): HIV status known prior to pregnancy in 50%; 83.3% of pregnancies unplanned 43% of these resulted from lack of contraception (Koenig LJ et al. Am J Obstet Gynecol. 2007;197(3 suppl):s123-s131)

7 Reproduced with permission from Massad LS et al. J Women s Health. 2007;16:

8 Contraceptive Use Among US Women With HIV (cont.) Reproduced with permission from Massad LS et al. J Women s Health. 2007;16:

9 Efficacy Safety Adverse effects Effect on HIV transmission Effect on HIV progression Drug interactions Convenience/ ease of use Cost Protection against other STDs Noncontraceptive benefits STD = sexually transmitted diseases.

10 Category 1 Use method in any clinical circumstances Category 2 With clinical judgment, generally use method With limited clinical judgment, use method Category 3 With clinical judgment, use of method not generally recommended unless more appropriate methods not available or acceptable With limited clinical judgment, do not use method Category 4 Do not use method WHO = World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva, Switzerland: World Health Organization; 2004.

11 COC/ P/R CIC POP DMPA LNGimpl Cu- IUD LNG- IUD High risk HIV AIDS /2 3/2 ART Rifampin Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva, Switzerland: World Health Organization; ACOG Practice Bulletin #117 Gynecologic Care for Women with Human Immunodeficiency Virus. December 2010 CIC = combined injectable contraceptives; COC/P/R = low-dose combined oral contraceptives/patch/ring; Cu-IUD = copper intrauterine devices; LNG-impl = levonorgestrel implants; LNG-IUD = levonorgestrelreleasing intrauterine devices; POC = progestogen-only pills.

12 Risk of birth defects with conception on EFV-containing regimens FDA pregnancy category D Teratogenic in primates Retrospective case reports of CNS defects in infants of women who received EFV at conception and during the first trimester Sufficient first trimester exposures to ABC, ddi, EFV, NFV, NVP, RTV, and d4t to detect 2 increase in defects EFV should be avoided during the first trimester, and in women at risk for becoming pregnant Pregnancy should be avoided in women receiving EFV ABC = abacavir; ACE = angiotensin-converting inhibitor; CNS = central nervous system; d4t = stavudine; ddi = didanosine; EFV = efavirenz; FDA = US Food and Drug Administration; MTX = methotrexate; NFV = nelfinavir; NVP = nevirapine; RTV = ritonavir; TCN = triciribine. Watts HD. Curr HIV/AIDS Rep. 2007;4:

13 Patient presented in 9/2011 with c/o amenorrhea for 2 months and now abnormal spotting hcg (+) Diagnosed with ectopic pregnancy, treated medically with success; however difficult to achieve follow-up

14 Presented again in 2/2012, reporting a desire to avoid pregnancy, but using condoms only 50% of the time Reported unfavorable side effects with DMPA, difficulty complying with daily COCs in past. Discussed other hormonal contraceptives and IUDs. Elected vaginal contraceptive ring, and reviewed risks/benefits/use with patient upon prescribing Reinforced consistent condom use

15 Condoms alone have higher failure rate in prevention of pregnancy with typical use than most other methods of birth control Typical failure rate in first year of use: male condom (15%); female condom (21%) COC (8%); DMPA (3%); transdermal patch (8%); vaginal ring (8%); LNG-IUD 5 year (0.1%) Diaphragm (+spermicides) (16%) Spermicides (29%) Sterilization: female (0.5); male (0.15%) Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva, Switzerland: World Health Organization; 2004.

16 Noncontraceptive benefits of hormonal methods Decrease iron deficiency anemia Increase menstrual regularity (or can avoid menses) (combined estrogen/progestin only) Increase bone density (combined estrogen/progestin) Decrease dysmenorrhea Decrease risk of pelvic inflammatory disease Decrease risk of ectopic pregnancy Decrease incidence of endometrial cancer Decrease incidence of ovarian cancer Decrease incidence of colorectal cancer Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva, Switzerland: World Health Organization; 2004.

17 Risk of birth defects with conception on EFVcontaining regimens Other potential teratogens: alcohol, statins, ACE inhibitors, warfarin, lithium, carbamazepine, MTX, megestrol, phenytoin, TCN, valproic acid, vitamin A ABC = abacavir; ACE = angiotensin-converting inhibitor; CNS = central nervous system; d4t = stavudine; ddi = didanosine; EFV = efavirenz; FDA = US Food and Drug Administration; MTX = methotrexate; NFV = nelfinavir; NVP = nevirapine; RTV = ritonavir; TCN = triciribine. Watts HD. Curr HIV/AIDS Rep. 2007;4:

18 Seroconcordant couples Less likely to use condoms consistently May be more likely to desire prevention of pregnancy Images courtesy of Jhpiego, an affiliate of Johns Hopkins University. Heard I et al. J Acquir Immune Defic Syndr. 2004;36:

19 Potentially less likely to use condoms consistently General population: more effective primary method for pregnancy prevention, less likely consistent use of male condoms 1-3 HIV+ women more likely than HIV- women to use dual methods simultaneously: (odds ratio, 2.7) 4 : no alcohol use associated with increased dual method use 1. Sangi-Haghpeykar H et al. Fam Plann Perspect. 1997;29:67-69, Roye CF. J Adolesc Health. 1998;23: Centers for Disease Control and Prevention. JAMA. 1992;268: Wilson TE et al. Sex Transm Dis. 2003;30:

20 Concerns About Dual Methods (cont.) Possible negative impact on adherence to ART with use of oral contraceptives Adverse effects: nausea Alternate routes of delivery hormonal birth control Injectable (DMPA) Implant (3 yr) Transdermal patch (1 wk) Vaginal ring (3 wk) Intrauterine system (5 yr)

21 Heffron et al Lancet 2012: Potential increased risk of HIV acquisition and transmission with hormonal contraceptives, especially injectable methods :3790 serodiscordant couples in 7 countries in East and Southern Africa were enrolled in an observational study of immune correlates of HIV-1 protection and followed for 2 years Administered questionnaire about contraceptive method, condom use, sexual frequency, outside partners, STIs, ART use, collected HIV RNA, CD4 count, performed rapid HIV testing and confirmatory tests Heffron R et al. Lancet Inf Dis 2012;12:19-26.

22 For most couples, HIV-1 infected partner was the female Median CD4 455, VL 4.10 log 10 C/mL 194 (15%) of HIV-1 seronegative and 430 (17%) of HIV-1 seropositive women used hormonal contraception, with most using DMPA

23 167 seroconversions occurred Rates of HIV acquisition were higher in women using hormonal contraception than in women who were not Any hormonal contraceptive: Adjusted hazard ratio 1.98 (CI ) Injectable: HR 2.05 (CI ) Rates of HIV transmission were higher in women using hormonal contraception than in women who were not HR 1.97 (CI )

24 Endocervical concentrations of HIV-1RNA were higher in women using injectable contraception than in women who were not, by an average of 0.19 log 10 C/swab, after adjusting for plasma HIV-1 concentrations but there was no association between contraceptive method and plasma HIV RNA levels Suggests a localized effect of hormonal contraception on increased concentrations of HIV-1 in the female genital tract possible changes to vaginal structure, cytokine regulation, CCR5 expression, cervico-vaginal HIV-1 shedding Need to counsel women about HIV-1 risk with hormonal contraception and the importance of dual protection with condoms Need data on other hormonal contraceptives (implants, patches, rings, combination injectables) as well as IUDs

25 Data on association of HC and HIV acquisition are conflicting Retrospective secondary analyses with possible selection bias, self-report of contraceptive method, confounding variables changes in HC use over time, presence of STIs HIV infected partner not on ARV Further study is needed to determine if HC use is an independent risk factor for acquisition and transmission of HIV Stress critical need for safe and effective contraceptives for HIV infected women, need for dual protection with condoms.

26 Conflicting data from prospective and cohort studies Cohort study of 285 Kenyan women on HC at time of HIV acquisition: HC not associated with elevated VL set point (J Acquir Immune Defic 2011;56(2):125) Prior cohort study of Kenyan women on DMPA showed higher viral set points and greater likelihood of multiple viral variants shortly after infection (J Acquir Immune Defic 2005;28 (Suppl1):S18) Cohort studies in US and Kenya showed HC was not associated with a change in VL over time (AIDS 2003;17:1702; AIDS 2007;21:749) Studies in general on women not on ART Full range of HC methods should be available for all women with HIV.

27 Drug interactions Decrease in steroid levels with concomitant administration Barbiturates (including phenobarbital, primidone) Phenytoin Carbamazepine Topiramate Rifampin/rifabutin Griseofulvin Increase in blood levels of co-existing drug Diazepam Tricyclics Theophylline Image courtesy of Jhpiego, an affiliate of Johns Hopkins University.

28 Hormonal contraceptive RTV-boosted PIs Effect on hormone level EE/norgestimate ATV/r EE AUC 19%, Cmin 37% NE level 85% EE/norethindrone DRV/r EE AUC 44% NE AUC 14% FPV/r EE AUC 37% NE AUC 34% Recommendation Need >=35 mcg EE Use alt or addn l method Use alt or addn l method LPV/r EE AUC 42% Use alt or addn l method *note HC with other progestins not studied. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for use of Antiretroviral agents in HIV-infected Adults and Adolescents. Department of Health and Human Services. Accessed on April 7, 2012

29 Hormonal contraceptive RTV-boosted PIs Effect on hormone level EE/norethindrone TPV/r EE AUC 48% NE Recommendation Use alt or addn l method Hormonal contraceptive SQV/r EE Use alt or addn l method PIs without RTV Effect on hormone level EE/norethindrone ATV EE AUC 48% NE AUC 110% FPV w/ APV EE and NE, APV 20% Recommendation Use HC w/ <30 mcg EE or alt method Use alt method *note OCs w/ <25 mcg EE or other progestins have not been studied. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for use of Antiretroviral agents in HIV-infected Adults and Adolescents. Accessed on April 7, 2012

30 HC NNRTI Effect on hormone level Recommendation EE/levonorgestrel EE/norelgestromin Etonogestrel (implant) Levonorgestrel (EC) EFV EE levonorgestrel AUC 83% norelgestromin AUC 64% Use alt or addn l method EFV possible Use alt or addn l method EFV AUC 58% Effect of EC may be EE/norethindrone ETR EE AUC 22%, NE NVP EE AUC 20% NE AUC 19% RPV DMPA NVP HC CCR5 antag MVC EE AUC 14%, NE Effect on hormone level EE or levo Use alt or addn l method Recommendation

31 Small studies with different formulations of HC Study doses often unclear or nonstandard, single ARV interactions and minimal data on new ARV classes Magnitude of change in drug levels that may reduce contraceptive efficacy or increase adverse effects are unknown More studies with alternative routes of HC delivery needed No clinical endpoints Guidelines for use of Antiretroviral agents in HIV-infected Adults and Adolescents. Accessed on April 7, 2012

32 Combined estrogen/progestin contraceptives Minor adverse effects: nausea, breast tenderness, bloating, headache usually self-limited Contraindications (estrogen/progestin) History of thromboembolic disease >35 years of age, smoker Hypertension Diabetes mellitus: age >35 years or <35 years with associated vascular disease Coronary artery disease/congestive heart failure/cerebrovascular disease Migraines: age >35 years or <35 years with focal neurologic signs Uncontrolled low-density lipoprotein cholesterol >160 mg/dl, triglycerides >250 mg/dl, or multiple other risk factors for coronary artery disease Active liver disease Progestin-only contraceptives Decreased bone density with DMPA (5% 7%); significant gains in bone mass after discontinuation Irregular bleeding Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva, Switzerland: World Health Organization; 2004.

33 Efficacy: /100 women at 12 months Safety Cu-IUD: effective for 10 years; LNG-IUD: effective for 5 years 599 postpartum HIV+ women in Zambia randomized to Cu-IUD vs hormonal contraception (followed up for at least 2 years) 1 Pregnancy more likely in hormonal contraceptive group (HR 2.4; 95% CI, ) No increase in cervical HIV shedding (measured 4 months after IUD insertion) 2, 5 No evidence of increased complications (unplanned pregnancy, infections) for HIV+ women; complications similar by CD4 cell counts 3,4,5 Improved hemoglobin with LNG-IUS, decreased bleeding 5 No interaction between LNG and ART 5 1. Stringer EM et al. Am J Obstet Gynecol.2007;197:144.e Richardson BA et al. AIDS.1999;13): Sinei SK et al. Lancet.1998;351: Morrison CS et al. Br J Obstet Gynaecol. 2001;108: Heikenheimo O et al. AJOG 20111;204:126.e1-4.

34 Should be considered when there is an episode of unprotected intercourse or broken condom Combined OCPs with EE and norgestrol/ levonorgestrel 0.75 mg/ulipristal acetate 30 mg reduces pregnancy by at least 74% Take within 72 hours No STI/HIV protection

35 Safe and effective contraception remains a priority for HIV-infected women and all methods should be available to them Dual method is best IUDs appear to be safe Hormonal contraceptive methods need to be assessed closely for use by a given HIV patient Particular care given to use of injectable contraceptives More research on hormonal contraceptives and risk of HIV transmission, acquisition, progression needed, as well as on ARV drug interactions

36 Jean Anderson, MD Jean Keller, PA-C Adriana Andrade, MD, MPH