RAMONA BHATIA, MD2013

Women’s Health in Resource-Limited Settings

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

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 NorthwesternResearch Associate at Center for Global

Health HIV outcomes HIV and global health

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

Addressing women’s health is a necessary andeffective approach to strengthening health

systemsoverall – action that will benefit everyone.

Improvingwomen’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

Top Global Causes of Mortality in WomenWHO, 2008

All agesRLS Lower respiratory infections (11%) >HIV/AIDS>

Diarrheal diseasesHigh income countries

Ischemic heart disease (15%)>Stroke>Alzheimer’s Disease

ChildrenRLS Lower respiratory infections (18%)>Diarrheal

diseases> MalariaHigh income countries

Congenital abnormalities (23%)>Prematurity and low birth weight>Neonatal infections

Top Global Causes of Mortality in WomenWHO, 2008

Adolescents RLS HIV/AIDS (10%) > Lower respiratory infections>

MalariaHigh income countries

Road traffic accidents (28%)>Suicide>Homicide

Adults RLS HIV/AIDS (23%)> TB> Maternal hemorrhageHigh income countries

Breast cancer (11%)>Lung, tracheal, or bronchial cancers>Ischemic heart disease

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

HIV and Women’s HealthWHO, 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

Mother to Child Transmission of HIVWHO, 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.

Total: 3.4 million [3.0 million – 3.8 million]

Europe19 000

[15 000 – 25 000]

Africa3.1 million

[2.8 million – 3.5 million]

South-East Asia140 000

[92 000 – 190 000]

Western Pacific39 000

[33 000 – 46 000]

Americas58 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]

Total: 250 000 [220 000 – 290 000]

Europe1 300

[<1 000 – 1 800]

Africa230 000

[200 000 – 260 000]

South-East Asia12 000

[6 800 – 18 000]

Western Pacific2 700

[2 200 – 3 400]

Americas3 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]

Antiretroviral Therapy (ART) for PMTCTWHO, 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

Disparities in PMTCTWHO, Progress Report, 2010

In the U.S., vertical transmission has been “virtually eliminated” Universal “opt-out” testing for HIV for all pregnant

womenIn RLS, only half of HIV+ pregnant women

receive ART for PMTCTOnly one-third of pregnant women are tested

for HIV in RLS WHO guidelines recommend early HIV testing Repeat testing indicated in third trimester

Percentage of pregnant women who received an HIV test in RLSWHO, 2011

Epidemic update and health sector progress towards Universal Access Progress Report

Coverage of antiretroviral medicine for PMTCT in RLS (2010)WHO, 2011

Epidemic update and health sector progress towards Universal Access Progress Report

Gaps in reaching 90% of HIV+ pregnant women on ART WHO, 2011

Epidemic update and health sector progress towards Universal Access Progress Report

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

PMTCT in the U.S.: antenatal and intrapartumDHHS, 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

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

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

PMTCT Regimens in RLS: treating the motherWHO, Executive Summary, 2012

For women with CD4 cell count <350/mm3 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

PMTCT Regimens in RLS: prophylaxis

For women with CD4>350/mm3, two optionsIn 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

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

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

PMTCT Options in RLSWHO, 2012

CD4<350 CD4>350 Infant Receives

Option A First line ART regimen

Antepartum: 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 B First line ART regimen

ART 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

First line ART regimen

Daily NVP or AZT from birth through age 4–6 weeks

PMTCT Summary

U.S. RLSVertical transmission Virtually zero 1,000 new childhood

infections/dayHIV testing in pregnant women

Universal, “opt-out” Approx. one-third tested

PMTCT for pregnant HIV+ women

Lifelong treatment Can be either lifelong treatment or prophylaxis

Infant prophylaxis Yes YesBreastfeeding for HIV+ mothers

Not recommended Country-dependent

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

PrEPWHO , 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

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

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 yetMany unanswered questions:

Duration Monitoring and HIV testing Side effects

Disparities in Maternal MortalityWHO, Trends in Maternal Mortality, 2012

WHO defines maternal death as: The death of a woman while pregnant or within 42 days of termination ofpregnancy, irrespective of the duration and site of the pregnancy, fromany cause related to or aggravated by the pregnancy or its managementbut not from accidental or incidental causes

In 2010, 287,000 maternal deaths occurred globally85% 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

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

Unsafe AbortionWHO, 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 unsafeWomen 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

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 safeHighest rates of abortion are in Latin

America/ Caribbean and Africa Almost exclusively unsafe in both regions

Morbidity and Mortality from Unsafe AbortionsWHO, 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 AfricaCase fatality rate for Africa=470/100,000 abortions

Case fatality rate for U.S.=0.6/100,000 abortionsOther morbidities include:

Infertility Genital trauma and development of fistulas, which can lead

to infection, stigma, etc.

Unsafe Abortion: implicationsWHO, Safe and Unsafe Induced Abortion, 2008

The number of unsafe abortions is increasingAvailability 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

Other Important Global Women’s Health Issues: cervical cancer

WHO, Cervical Cancer, HPV, and HPV Vaccines, 2008

Due to HPV; sexually transmittedThe 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

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 womenWHO, Multi-country Study on Women’s Health, 2005

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.

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?

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 issuesWomen face unique challenges in RLS including an

excessive burden of infectious diseasesPMTCT is crucial to controlling HIV in RLSEmpowerment through education (i.e., family

planning, contraception, domestic violence support, etc.) is critical Medical students can help with this

http://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.

For a list of topics for “other” sectionhttp://www.who.int/reproductivehealth/

publications/en/