HIV AND WOMEN’S HEALTH Anandi Sheth, MD Emory University Division of Infectious Diseases October 15, 2013 Epidemiology – Global  ~50% of people living with HIV are women  ~47% of new infections occur in women  Disproportionate impact on women in sub-Saharan Africa  Particularly among young women (3-8 times increased HIV, AIDS leading cause of death) Women >15yo living with HIV, 1990 Women >15yo living with HIV, 2012 www.unaids.org Epidemiology - US    Shift towards increased HIV incidence in women in the US (now ~20% of new cases) Racial disparities are magnified in women Higher-than-expected concentrations in the Southern US Women and HIV Transmission  Sociobehavioral factors: May not be able to negotiate consistent condom use  Violence increases HIV risk through multiple mechanisms  Stigma, poverty, substance abuse, other comorbid conditions   Biological factors:  Higher risk of HIV acquisition than men during vaginal sex Large surface area  Concomitant STIs/ inflammation/ mucosal trauma  Hormonal effects on mucosa   High risk of transmission during anal sex Access to Care and Natural History   Data are mixed, but some studies suggest gender differences in timing of diagnosis, access to care, progression to AIDS Barriers to entry and retention in care  Transportation, child care, work schedules, economics, insurance, stigma, mental health/ substance abuse ART in Women    Generally, response to ART is comparable between men and women Adherence also similar, though may have different reasons for non-adherence Women may have increased risk of ART-associated complications       Lactic acidosis due to NRTIs Rash and hepatitis due to nevirapine use discouraged in women with CD4>250 (>400 for men) PI-associated nausea/vomiting Bone loss Fat accumulation In general, treatment guidelines are the same for men and women with few exceptions HIV-associated conditions unique to women  Candida vulvovaginitis (recurrent) – most common presenting sx of HIV infection in women!  Cervical dysplasia and cancer  Recurrent/ complicated PID  Increased frequency/ severity of genital HSV  Increased/ persistent BV  Abnormal uterine bleeding  AIDS-defining conditions: invasive cervical cancer, genital tract TB, genital tract lymphoma, other genital tract OI (ex., CMV endometritis)  Screen for GU disease routinely (q6mo-annual), after potential exposures or new sexual partner Case 1 35yoF with HIV, newly diagnosed, CD4=387, VL 27K, presents for new patient appointment. She was diagnosed by routine testing with her PCP, has no history of abnormal Pap or genital HPV, and is asymptomatic. How should she be screened for cervical dysplasia? A. Pap and HPV testing now. If normal, repeat annually. B. Pap now. If normal, repeat in 6 months. C. Pap now. If abnormal, repeat in 6 months. D. Colposcopy now. E. Pap now. If abnormal, colposcopy in 6 months. HPV-related disease in HIV-infected women  Clinical manifestations of HPV infection:      Oral, genital, and anal warts (condyloma acuminata) Cervical, vaginal, vulvar, anal dysplasia and cancers, subset of oropharyngeal cancers HIV-infected women are ~10x more likely to have abnormal Pap than HIV-uninfected women Increased persistence of HPV and/or progression of dysplasia, higher cervical cancer risk Genital warts, vulvar dysplasia, and anal dysplasia (~25%) also common! Credit: AETC HIV Screening and Women’s Health Screening Guidelines in HIV-infected women  Screen with Pap every 6 months in the first year after diagnosis  Screen annually afterwards  Consider screening within 1 year of onset of sexual activity regardless of age  After hysterectomy, do vaginal cuff Pap if patient has history of CIN or cervical CA  Colposcopy depending on cytology +/- HPV DNA per guidelines   Role of HPV testing (detects most oncogenic HPV types) in HIV-infected women has not been established Limited data on HPV vaccine (studies underway), recommended for HIV-infected males & females 13-26 (prefer <19)  Differ from guidelines for HIV-negative women (extend screening interval to 3-5 years in women >30yo with normal cytology and negative oncogenic HPV DNA test results) Should screening guidelines change for some HIV-infected women?  420 HIV-infected vs. 279 uninfected women HIV-  Enrolled 2001-2002 after widespread use of HAART  Normal cervical cytology at enrollment, HPV testing performed  Conducted q6month Pap testing with appropriate follow-up  Results: similar (and low) 5-year cumulative incidence of cervical precancer or cancer (HSIL+ or CIN2+) in oncogenic HPV-negative HIV-infected vs. -uninfected women Case 2 26yoF with HIV, CD4=300, VL undetectable on atripla. She is planning to get pregnant in the next 1 year. You should recommend that she do the following: A. Continue atripla because her VL is undetectable B. Discontinue atripla because tenofovir may be teratogenic. C. Discontinue atripla because efavirenz may be teratogenic. D. Continue atripla until she conceives. Then hold ART during the first trimester. E. She should receive a regimen containing zidovudine. When does mother-to-child transmission occur?  Overall risk of transmission without treatment - ~25%  In utero    <14 weeks (4%) 14-36 weeks (16%) 36 weeks+ (50%) ***  Intra-partum (30%)  Breastfeeding (?)  Conditions that may increase risk: maternal viral load, maternal genital tract infections/ inflammation, prolonged rupture of membranes PACTG 076: Zidovudine for prevention of mother-to-child transmission  477 pregnant HIV-infected women received AZT versus placebo as below:       100mg po 5x per day from 14-34 weeks Intrapartum 2mg/kg iv x 1 followed by 1mg/kg until delivery 6 weeks oral for infant (2mg/kg q6h for 6 weeks started 8-12h after birth Study halted in 1994 when 66% reduction in transmission noted in treatment group (7.6% versus 22.6) Became the standard for comparison of other regimens Subsequent regimens including cART have reduced transmission to <2% (see pages B7-B15 of perinatal guidelines (http://aidsinfo.nih.gov/guidelines) for a complete list of studies Current guidelines to reduce perinatal transmission  Opt-out testing for pregnant women  Pregnancy increases HIV acquisition risk, so repeat HIV test in the 3rd trimester in at-risk women!  If woman presents without antenatal care, do rapid test, initiate prophylaxis in mother and infant if rapid test is positive (do not wait for confirmatory test)   Assess for risk factors for transmission: plasma viremia, genital infections, drug use, unprotected sex Screen for Hepatitis B and C Current guidelines to reduce perinatal transmission, continued      All pregnant women start ART regardless of CD4 and VL (see next slide) Intravenous AZT during delivery C section at 38 weeks if VL >1000 copies/mL (at 39 weeks of other indication for C-section) Avoid invasive fetal monitoring, vacuum delivery or forceps during vaginal delivery, avoid artificial or prolonged ROM Postpartum care:    Continue ART (if CD4>500 discuss with patient) Avoid breastfeeding if access to clean water and formula Counsel on contraception ART during pregnancy NRTIs All drugs listed have high placental transfer to the fetus Preferred Zidovudine, lamivudine *If Hep B co-infected: tenofovir + lamivudine/emtricitabine Alternative Abacavir, emtricitabine ,tenofovir NNRTIs Preferred Nevirapine (not if CD4>250 or baseline transaminmitis) Special circumstances Efavirenz (Class D- test for pregnancy before initiating EFV-containing regimens, do not use in women who are planning to become pregnant, may be continued in women who are undetectable presenting for ant PIs Preferred Atazanavir/ ritonavir, lopinavir/ritonavir: dose adjust in the 2nd-3rd trimester Alternative Darunavir/ ritonavir Other classes Use in special circumstances (insufficient data, no known teratogenicity)    In general: if a women is controlled already, continue the regimen: Monitoring: VL baseline, 2-4 weeks after ART start or change, monthly until undetectable, q3mo during pregnancy, and at 34-36weeks to decide on mode of delivery If amniocentesis is needed- do after effective ART and VL undetectable WHO Guidelines (2010, 2013)     2010: start ART for all pregnant women with CD4<350 or stage 3/4 disease at 14 weeks, continue lifelong 2013: all pregnant women regardless of CD4 count start ART AZT/3TC or TDF/3TC plus NVP or EFV  2013 changed to TDF+3TC/FTC+EFV Two options for prophylaxis (2010):    Option A: twice daily AZT for mother and AZT or NVP for infant for 6 weeks or until 1 week after end of breastfeeding Option B: three-drug prophylaxis for mother during pregnancy and breastfeeding, and infant prophylaxis for 6 weeks after birth regardless of breastfeeding Option B+: mother continues three-drug treatment for life Reproductive options for HIV sero-discordant couples Perinatal guidelines: http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf Case 3 24yoF with perinatal HIV infection complicated by poor adherence and multi-class resistance. She was lost to follow-up 2 years ago, during which she became pregnant, was started on ARVs without VL suppression during pregnancy. She has been off ARVs since time of delivery, presented to resume care, CD4=8, VL 189K. She is sexually active with 1 male partner and inquires about contraception options. Which of the following is true: A. Combination oral contraceptives will be less effective due to ART B. Starting oral contraception will increase risk of HIV transmission to her male partner C. An IUD is contraindicated because it will increase her risk of PID D. Injectable contraceptives are associated with increased risk of HIV disease progression E. All of the above F. None of the above Importance of Family Planning in PMTCT UNAIDS 2006 Medical eligibility criteria for contraceptive use  WHO 1: Use without restriction  WHO 2: Can use (advantages outweigh risks)   WHO 3: Don’t use unless you have to (Risks outweigh advantages) WHO 4: Do not use (Unacceptable health risk) Our patients may have other conditions (besides HIV/AIDS or ARV use) that affect contraceptive eligibility MMWR vol 59 (2010); WHO 2009 Barrier methods  Condoms (WHO 1)      Spermicides/microbicides (WHO 3/4)    Latex condom failure rate ~15% with typical use (2% perfect use) Rupture 0.5-4% (deterioration, poor storage, oil lubricants) Failure rate similar for female condom, acceptability less Dual method recommended for HIV+ women (condom plus other) Increased risk of STI (HIV) acquisition Studies in progress Diaphragm/ cervical cap (WHO 3/4)   Failure rate 19-32% with typical use Requires spermicide Combined Hormonal Methods  Combined Pills  Efficacy ?reduced by abx (backup first 2 wks of TMP/SMX)  Overall, no increased HIV transmission/ acquisition risk  Vaginal ring (Nuvaring)  Active  for 3-5 weeks, need backup if removed >3 hours Patch (Evra)  Active for up to 9 days  Higher failure in women >90 kg Failure 8% (typical use), 0.3% (perfect use) NRTIs (WHO 1), NNRTIs (WHO 2), RTV-boosted PI (WHO 3) Progestin-only  Pills     Injectable (Depo-provera)      Failure rate same as combined methods Side effects: irregular bleeding, less forgiving if taken late, mood NRTIs (WHO 1), NNRTIs (WHO 2), RTV-boosted PI (WHO 3) Failure 3% with typical use (0.3% perfect use) Side effects: irregular bleeding, weight gain, hair loss ? Risk of CIS with long-term use if persistent HPV infection WHO 1 for all ARVs Insert (Implanon)     Lasts 3 years Failure 0.05% Side effects: irregular bleeding WHO 1/2 for all ARVs IUDs  Copper Failure 0.8%  Lasts 10-12 years  Side effect: irregular bleeding  May have decreased disease progression compared with hormonal methods   Levonorgestrel intrauterine system (Mirena) Releases hormone locally  Failure 0.2%  Lasts 5 years, can become pregnant as soon as its removed  Improves dysmenorrhea, decreased menstrual flow (long term)   May have short term increased menstrual irregularity Both: WHO 2 (except if AIDS WHO 3 because of ?increased PID risk) Drug Interactions with ARVs  NRTIs, RAL, MVC: all methods ok  NNRTIs     EFV ↓ norgestimate metabolites (many oral)- don’t use; possibly ↓ etonogestrel (implant), ↓ levonorgestrel (emergency contraception) NVP guidelines conflicting but probably ok ETR/RPV ok Boosted PIs   In general, ↓ethinyl estradiol and progestin (except ATV) Don’t use oral methods with any except     ATV/r (≥35mcg of ethinyl estradiol in combined) ATV (≤ 30 mcg ethinyl estradiol in combined) DMPA ok, implants not studied Stribild  ↑ progestin, ↓ ethinyl estradiol consider alternative because possible increase side effect of progestin  Some data suggest ovulation still suppressed even if ethinyl estradiol is decreased!  Effect on ART efficacy not well studied (monitor carefully…)  Check for drug interactions with other meds and for other medical contraindications! Intersection between HIV and intimate partner violence (IPV) CDC Definition: Physical, sexual, or psychological harm by a current or former partner or spouse. This type of violence can occur among heterosexual or same-sex couples and does not require sexual intimacy. IPV and HIV risk: how are they linked? Intimate partner violence Childhood abuse coping strategy increased vulnerability Substance abuse Less condom negotiation transactional sex i.e. intravenous drug use Increased sexual partners ? STI/HIV infection Courtesy of A Kalokhe High IPV prevalence in HIV-infected populations   IPV prevalence among HIV-infected populations ranges from 39-93% Among inpatient HIV+ crack cocaine users from Atlanta and Miami, 56% reported any IPV, 26% reported severe IPV  IPV associated with increased unprotected sex, increased STIs, and not using ART  38% did not use any IPV resources Kalokhe et al 2012 Screening for IPV (adapted from a validated screener: Paranjape A. J Natl Med Assoc. 2006 ) Were you ever in a relationship in which: 1. a sexual partner beat, physically attacked, or physically abused you? 2. a sexual partner sexually attacked, raped, or sexually abused you? 3. a sexual partner threatened you with violence (i.e. acts of aggression or abuse that were meant to harm you)? 4. a sexual partner threw, broke, or punched things? 5. you felt controlled by a sexual partner? Courtesy of A Kalokhe Types of IPV experienced Reported being in a relationship in which: Male (n=170) Female (n=173) Total (n=343) a sexual partner was physically abusive 20 (12%) 74 (43%) 94 (27%) a sexual partner was sexually abusive 10 (6%) 50 (29%) 60 (17%) a sexual partner threw, punched, or broke things 64 (38%) 96 (56%) 160 (47%) a sexual partner threatened the participant with violence 49 (30%) 100 (58%) 149 (43%) felt controlled by a sexual partner 45 (27%) 97 (56%) 143 (42%) Courtesy of A Kalokhe Short, Easy, Sensitive and Specific IPV Screening Tools: find them on-line • HITS (Hurt, Insult, Threaten, Scream) • STaT (Slapped, Threatened, and Throw): developed at Grady! • HARK (Humiliation, Afraid, Rape, Kick) • CTQ-SF (Modified Childhood Trauma Questionnaire–Short Form) • WAST (Woman Abuse Screen Tool) Courtesy of A Kalokhe IPV Resources at IDP and beyond       Discussion is encouraged during HIV pre-test counseling IPV risk assessment is required for post-test counseling Consider poor adherence, missed visits, etc. as a proxy for IPV Also consider when you are discussion HIV status disclosure, safe sex counseling At IDP: Mental health, substance abuse, financial counseling Referral to IPV services  Partnership Against Domestic Violence has a 24-hour crisis line: 404-873-1766 Thanks!     Igho Ofotokun Lisa Haddad Ameeta Kalokhe SEATEC