1. RAMONA BHATIA, MD 2013 Women’s Health in Resource- Limited Settings

2. Outline Introduction to international women’s health issues HIV  Prevention of maternal to child transmission (PMTCT)  Pre-exposure prophylaxis (PrEP) Other maternal issues  Unsafe abortion Other women’s health issues

3. Introduction Undergraduate and medical training at Northwestern  Clinical experience in India Residency at Baylor College of Medicine, Houston, TX  County and VA hospital settings Infectious Diseases Fellow at Northwestern Research Associate at Center for Global Health  HIV outcomes  HIV and global health

4. Importance of Women’s Health In many resource-limited settings (RLS), there is a lack of access to ob-gyne specialists Physicians must manage all aspects of health care, including gyne and ob issues Students on almost every rotation will be expected to care for women and deal with women’s health problems

5. Addressing women’s health is a necessary and effective approach to strengthening health systems overall – action that will benefit everyone. Improving women’s health matters to women, to their families, communities and societies at large. Improve women’s health – improve the world. Importance of Women’s Health --WHO, Women and Health, 2009

6. Top Global Causes of Mortality in Women WHO, 2008 All ages RLSLower respiratory infections (11%) >HIV/AIDS> Diarrheal diseases High income countries Ischemic heart disease (15%)>Stroke>Alzheimer’s Disease Children RLSLower respiratory infections (18%)>Diarrheal diseases> Malaria High income countries Congenital abnormalities (23%)>Prematurity and low birth weight>Neonatal infections

7. Top Global Causes of Mortality in Women WHO, 2008 Adolescents RLSHIV/AIDS (10%) > Lower respiratory infections> Malaria High income countries Road traffic accidents (28%)>Suicide>Homicide Adults RLSHIV/AIDS (23%)> TB> Maternal hemorrhage High income countries Breast cancer (11%)>Lung, tracheal, or bronchial cancers>Ischemic heart disease

8. Global Trends in Women’s Health In low-income countries, mortality is mainly associated with infectious diseases [with] trends towards non-communicable diseases and injuries in higher-income countries. -WHO, 2008

9. HIV and Women’s Health WHO, 2010; CDC.gov In 2008, 15.7 million women living with HIV/AIDS globally  12 million in sub-Saharan Africa In sub-Saharan Africa, women account for 60% of HIV infections  Approx. 20% in U.S. Women’s HIV issues:  Vertical transmission in pregnancy  Serodiscordance and PrEP  Stigma and fear of disclosure  Problems accessing HIV care

10. Mother to Child Transmission of HIV WHO, 2008; CDC.gov HIV is transmitted in utero, at labor and delivery, or through breastfeeding  Overall 15-30% risk (30% in utero and 70% intrapartum)  Breastfeeding additional 5-20% Almost all (>90%) childhood HIV is due to maternal transmission In 2008, 1.4 million HIV+ women gave birth in RLS, and there were 430,000 new pediatric infections  90% of pediatric cases and deaths in Sub-Saharan Africa In 2005, 142 children contracted HIV from their mothers in the U.S.

11. Total: 3.4 million [3.0 million – 3.8 million] Europe 19 000 [15 000 – 25 000] Africa 3.1 million [2.8 million – 3.5 million] South-East Asia 140 000 [92 000 – 190 000] Western Pacific 39 000 [33 000 – 46 000] Americas 58 000 [44 000 – 74 000] Children (<15 years) estimated to be living with HIV, by WHO Region, 2010 Eastern Mediterranean 42 000 [28 000 – 57 000]

12. Total: 250 000 [220 000 – 290 000] Europe 1 300 [<1 000 – 1 800] Africa 230 000 [200 000 – 260 000] South-East Asia 12 000 [6 800 – 18 000] Western Pacific 2 700 [2 200 – 3 400] Americas 3 600 [2 100 – 5 100] Estimated deaths in children (<15 years) from AIDS, by WHO Region, 2010 Eastern Mediterranean 4 100 [2 800 – 5 500]

13. Antiretroviral Therapy (ART) for PMTCT WHO, PMTCT Strategic Vision, 2010 ART prophylaxis reduces risk of vertical transmission to <2% PMTCT with ART is the cornerstone of caring for HIV+ pregnant women globally Other interventions:  Primary prevention of HIV in women  Testing ALL pregnant women for HIV  Family planning and prevention of unwanted pregnancies in HIV+ women

14. Disparities in PMTCT WHO, Progress Report, 2010 In the U.S., vertical transmission has been “virtually eliminated”  Universal “opt-out” testing for HIV for all pregnant women In RLS, only half of HIV+ pregnant women receive ART for PMTCT Only one-third of pregnant women are tested for HIV in RLS  WHO guidelines recommend early HIV testing  Repeat testing indicated in third trimester

15. Epidemic update and health sector progress towards Universal Access Percentage of pregnant women who received an HIV test in RLS WHO, 2011 Epidemic update and health sector progress towards Universal Access Progress Report

16. Epidemic update and health sector progress towards Universal Access Coverage of antiretroviral medicine for PMTCT in RLS (2010) WHO, 2011 Epidemic update and health sector progress towards Universal Access Progress Report

17. Epidemic update and health sector progress towards Universal Access Gaps in reaching 90% of HIV+ pregnant women on ART WHO, 2011 Epidemic update and health sector progress towards Universal Access Progress Report

18. ART for PMTCT Antiretroviral (ARV) drugs reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load and providing infant pre- and post-exposure prophylaxis. Therefore, combined antepartum, intrapartum, and infant ARV prophylaxis is recommended to prevent perinatal transmission of HIV. -DHHS, 2012

19. PMTCT in the U.S.: antenatal and intrapartum DHHS, 2012 HIV+ pregnant women are started ART  Usually ASAP; definitely before 14 weeks (second trimester)  Preferred regimen depends on resistance, side effects, etc.  Efavirenz (EFV) is avoided due to neural tube defects  ART usually continued for life They also receive intravenous zidovudine (AZT) during labor and delivery C-section is recommended for women with untreated HIV or a viral load of >1,000/mL

20. PMTCT in the U.S.: infant care Within 12 hours of birth, the infant is given AZT  This is continued for 6 weeks The infant undergoes HIV testing at 14-21 days, 1-2 months, and 4-6 months

21. PMTCT in RLS vs U.S. WHO, Rapid Advice, 2009 Universal ART to treat pregnant women is not the norm for RLS, which represents a major difference from the U.S. standard of care In RLS, PMTCT can be accomplished by either fully treating the mother as in the U.S. OR administering a prophylaxis regimen to the mother  With both strategies, infants receive prophylaxis

22. PMTCT Regimens in RLS: treating the mother WHO, Executive Summary, 2012 For women with CD4 cell count <350/mm 3 or WHO Stage 3 or 4, initiate lifelong ART  Recommended regimens the same as for non-pregnant adults  AZT, lamivudine (3TC), and nevirapine (NVP) or EFV Recent updated WHO guidelines have added “Option B+” for all pregnant HIV+ women to receive lifelong ART irrespective of CD4 cell count

23. PMTCT Regimens in RLS: prophylaxis For women with CD4>350/mm 3, two options In Option A, AZT started at 14 weeks, single-dose NVP given at labor, and AZT/3TC given at labor and daily through 7 days postpartum In Option B, ART starting as early as 14 weeks and continued intrapartum and through childbirth if not breastfeeding or until 1 week after cessation of all breastfeeding

24. PMTCT Regimens in RLS: prophylaxis given to the infant In Option A, NVP from birth until 1 week after cessation of all breastfeeding; or, if not breastfeeding or if mother is on treatment, through age 4–6 weeks In Options B and B+, NVP or AZT from birth through age 4–6 weeks The infant is tested at for HIV after birth

25. Breastfeeding Risk factors that increase HIV transmission:  Duration of breastfeeding  Skin breakdown/mastitis  Maternal HIV viral load In the U.S., HIV+ mothers are counseled not to breastfeed In RLS, each country decides what will result in highest rates of “HIV-free survival of HIV-exposed infants”  In RLS, antibodies from breast milk help combat infectious diarrhea If breastfeeding is chosen:  Mother or infant should be on ART for at least duration  Exclusive breastfeeding should occur for first 6 months  Breastfeeding should stop only when a adequate and safe diet can be provided

26. PMTCT Options in RLS WHO, 2012 CD4<350CD4>350Infant Receives Option AFirst line ART regimenAntepartum: AZT starting as early as 14 weeks gestation Intrapartum: at onset of labor, single-dose NVP and first dose of AZT/3TC Postpartum: daily AZT/3TC through 7 days postpartum Daily NVP from birth until 1 week after cessation of all breastfeeding; or, if not breastfeeding or if mother is on treatment, through age 4–6 weeks Option BFirst line ART regimenART starting at 14 weeks gestation and continued intrapartum and through childbirth or 1 week after breastfeeding Daily NVP or AZT from birth through age 4–6 weeks Option B+First line ART regimen Daily NVP or AZT from birth through age 4–6 weeks

27. PMTCT Summary U.S.RLS Vertical transmissionVirtually zero1,000 new childhood infections/day HIV testing in pregnant women Universal, “opt-out”Approx. one-third tested PMTCT for pregnant HIV+ women Lifelong treatmentCan be either lifelong treatment or prophylaxis Infant prophylaxisYes Breastfeeding for HIV+ mothers Not recommendedCountry-dependent

28. PrEP Women usually acquire HIV via heterosexual sex  Serodiscordant couples (particularly if partner not on ART)  Partner non-disclosure or unawareness  Lack of condoms due to unavailability or loss of power  Sexual abuse or violence HIV post-exposure prophylaxis (PEP) has been used in cases of unanticipated HIV exposure PrEP recently approved for some anticipated HIV exposures

29. PrEP WHO, Guidance on PrEP, 2012 High quality data on tenofovir (TDF)/emtricitibine (FTC; Truvada) on prevention of HIV in high-risk male homosexuals and serodiscordant couples iPrEx trial: 90% HIV reduction in men who have sex with men who were adherent to Truvada Partners PrEP trial: 90% HIV reduction in serodiscordant couples who were adherent to Truvada

30. PrEP In July 2012, Truvada FDA approved for PrEP for men who have sex with men and heterosexually active women and men In June 2013, the CDC added an indication for injection drug users

31. PrEP In women, PrEP could be useful for women to protect themselves in cases where partner is not on ART or where conception is desired Not widely used in U.S. and RLS yet Many unanswered questions:  Duration  Monitoring and HIV testing  Side effects

32. Disparities in Maternal Mortality WHO, Trends in Maternal Mortality, 2012 WHO defines maternal death as: The death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes In 2010, 287,000 maternal deaths occurred globally 85% of these occurred in RLS including:  Sub-Saharan Africa (56%)  Asia (29%) Two countries accounted for a third of global maternal deaths: India at 19% (56,000) and Nigeria at 14% (40,000) Lifetime risk of maternal death in RLS is 1/150  1/3800 in developed world

34. Causes of Maternal Mortality In RLS, top etiologies include:  Hemorrhage (34%)  Infection (10%)  HTN (9%)  HIV/AIDS (6%)  Unsafe abortion (4%) The main obstacle to progress for better health for mothers is the lack of skilled care

35. Unsafe Abortion WHO, Safe and Unsafe Induced Abortion, 2008 Globally, 210 million pregnancies occur each year  80 million are unintended  86% of abortions occur in RLS  43.8 million induced abortions in 2008: 22.2 million safe and 21.6 million unsafe Women in RLS may not have access to safe, legal, affordable abortion facilities and may resort to unskilled or traditional practitioners The WHO defines unsafe abortion as: a procedure for terminating an unintended pregnancy carried out either by persons lacking the necessary skills or in an environment that does not conform to minimal medical standards, or both

36. Disparities in Unsafe Abortion Almost all unsafe abortions take place in developing countries In 2008, 38 million induced abortions in developing countries  21 million (56%) were unsafe and 17 million (44%) were safe Highest rates of abortion are in Latin America/ Caribbean and Africa  Almost exclusively unsafe in both regions

37. Morbidity and Mortality from Unsafe Abortions WHO, Safe and Unsafe Induced Abortion, 2008 5 million women are hospitalized each year and 47,000 women die due to complications of unsafe abortion  1 maternal death per 500 unsafe abortions 62% of these deaths in Africa Case fatality rate for Africa=470/100,000 abortions  Case fatality rate for U.S.=0.6/100,000 abortions Other morbidities include:  Infertility  Genital trauma and development of fistulas, which can lead to infection, stigma, etc.

38. Unsafe Abortion: implications WHO, Safe and Unsafe Induced Abortion, 2008 The number of unsafe abortions is increasing Availability of effective contraceptive methods results in reducing unintended pregnancies and the incidence of abortion Three out of four induced abortions could be eliminated if the need for family planning were fully met Restrictive abortion laws are correlated with high mortality from abortion

39. Other Important Global Women’s Health Issues: cervical cancer WHO, Cervical Cancer, HPV, and HPV Vaccines, 2008 Due to HPV; sexually transmitted The leading cause of cancer death of adult women in the developing world and the second most common cancer among women worldwide 80% of cases and highest mortality in RLS  Sub-Saharan Africa highest incidence  India highest number of cases Virtually no screening and/or treatment in many developing countries

40. The UN/WHO define violence against women as: any act of gender-based violence that results in, or is likely to result in, physical, sexual or mental harm or suffering to women, including threats of such acts, coercion or arbitrary deprivation of liberty, whether occurring in public or in private life WHO study shows up to 60% of women experience sexual or other physical violence by a male partner  Highest rates in Peru and Ethiopia; lowest in Japan Most common reasons for not seeking help include thinking violence is normal and fear of repercussions Other Important Global Women’s Health Issues: violence against women WHO, Multi-country Study on Women’s Health, 2005

41. Case WHO.org Mary is a 16 year old female with HIV who is 20 weeks pregnant with her second child. She is coming to see you in the family practice clinic in Cape Town. She has not seen a physician for prenatal care. She feels well. She takes no medications and has no other medical problems. Her physical examination is normal. She is very worried about her baby being born with HIV.

42. Discussion What can you tell her about her risk for HIV transmission to the baby? How can she reduce this risk? What other counseling does she need?

43. Summary In RLS, women’s morbidity and mortality are largely preventable and due to a lack of skilled care/resources  So visiting med students will be expected to help manage these issues Women face unique challenges in RLS including an excessive burden of infectious diseases PMTCT is crucial to controlling HIV in RLS Empowerment through education (i.e., family planning, contraception, domestic violence support, etc.) is critical  Medical students can help with this

45. http://aidsinfo.nih.gov/contentfiles/lvguidelines /peri_recommendations.pdfhttp://aidsinfo.nih.gov/contentfiles/lvguidelines /peri_recommendations.pdf 2012 For serodiscordant couples who want to conceive, expert consultation is recommended so that approaches can be tailored to specific needs, which may vary from couple to couple (AIII). It is important to recognize that treatment of the infected partner may not be fully protective against sexual transmission of HIV. Partners should be screened and treated for genital tract infections before attempting to conceive (AII). For HIV-infected females with HIV-uninfected male partners, the safest conception option is artificial insemination, including the option of self-insemination with a partner’s sperm during the peri-ovulatory period (AIII). For HIV-infected men with HIV-uninfected female partners, the use of sperm preparation techniques coupled with either intrauterine insemination or in vitro fertilization should be considered if using donor sperm from an HIV- uninfected male is unacceptable (AII). For serodiscordant couples who want to conceive, initiation of antiretroviral therapy (ART) for the HIV- infected partner is recommended (AI for CD4 T-lymphocyte (CD4-cell) count ≤550 cells/mm3, BIII for CD4-cell count >550 cells/mm3). If therapy is initiated, maximal viral suppression is recommended before conception is attempted (AIII). Periconception administration of antiretroviral pre-exposure prophylaxis (PrEP) for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission (CIII). The utility of PrEP of the uninfected partner when the infected partner is receiving ART has not been studied.

46. For a list of topics for “other” section http://www.who.int/reproductivehealth/publication s/en/