10/27/2014

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Going, Going, Not Quite Gone…The Race to End Perinatal HIV 

TransmissionCarol A. Vincent, PhD, CRNP, AAHIVS

The Children’s Hospital of Philadelphia

Objectives

• Describe how current trends in the HIV epidemic impact HIV in women and children in the United States

• Discuss current standards of care for the prevention of mother to child HIV transmission.

• Recognize psychosocial issues related to HIV testing and infection in pregnant women.

• Using case scenarios, describe the Nurse Practitioner’s role in implementation standards of care in prevention of perinatal transmission and pharmacologic management of HIV prevention medications as they relate to the case scenarios. 

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Percentages of HIV Cases Diagnosed Among Female Adults and Adolescents, by Transmission Category

2010—46 States and 5 US-Dependent Areas

Note:  Data include persons with a diagnosis of HIV infection regardless of their AIDS status at diagnosis. Data from 46 states with confidential name‐based HIV infection reporting since at least 2003. Data have been adjusted for reporting delays and missing risk‐factor information.*Heterosexual contact with a person known to have, or to be at high risk for, HIV infection.†Includes blood transfusion, perinatal exposure, and risk factor not reported or not iden fied.   Source CDC website

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Estimated Numbers and Percentages* of AIDS Cases Among Female Adults and Adolescents

1985–2010—United States and Dependent Areas

Year of diagnosis

Cas

es,N

o.

Cas

es,%

20071985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2003 2004 2005 20062001 2002 2008 2009 2010

Note:  Data have been adjusted for reporting delays.*Percentage of all cases that were diagnosed among females.

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AIDS Cases Among Female Adults and AdolescentsAttributed to Injection Drug Use or High-Risk Heterosexual

Contact, by Region, 2003–2007—50 States and DC

4

Northeast Midwest South WestRegion

16

20

12

8

0

Note:  Data have been adjusted for reporting delays and missing risk‐factor information. * Heterosexual contact with a person known to have, or to be at high risk for, HIV infection.

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Global HIV Rates● There are an estimated 34 million people infected with HIV● Worldwide, of people living with HIV, the percentage of

women with HIV remains at 50%● Nearly 68% of all people with HIV globally live in sub-

Saharan Africa ● 70% of AIDS deaths in 2011 occurred in sub-Saharan Africa● In sub-Saharan Africa, women make up nearly 60% of those

with HIV infection● Nearly 15 million children

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Female Health Disparities• Females account for an increased proportion of HIV cases in U.S.

– In 2010‐2011, 25% of HIV/AIDS patients were female– Increased from 23% in 2007 and 14% in 1992

• Changes in transmission risk– Increased heterosexual contact– Decreased IDU

• Continued disproportionate impact on African American womenLifetime risk:

– 1 in 32 African American women (decreased in 2010)– 1 in 106 Hispanic women– 1 in 526 Caucasian women 

Pediatric HIV Infection: Mother to Child Transmission

Pediatric AIDS Clinical Trials Group 076

A phase III randomized placebo-controlled trial of zidovudine (ZDV) for preventing maternal-fetal HIV transmission.Treatment Regimen

●Antepartum: 100 mg ZDV po 5x day, started at 14–34 weeks gestation

●Intrapartum: During labor, 1-hour initial dose 2 mg/kg IV followed by continuous infusion of 1 mg/kg until delivery

●Postpartum/Infant: 2 mg/kg po q 6 hr for 6 weeks, start 8–12 hours after birth

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Results of Pediatric AIDS Clinical Trials Group 076

● Intervention led to a 66% reduction in risk for transmission (P=

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Research to Implementation: # of HIV‐infected Infants and MTCT Rate in NY State by year of delivery, 1997‐2011

• Source: AIDS Institute, New York State Department of Health, 2012 

We are doing better but…how do we get to zero?... and how do we stay 

there?

HIV Cascade

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Prevention of Perinatal HIV ● With maternal diagnosis and prophylaxis

during the perinatal period, perinatal HIV transmission is usually preventable in all but 2% or less cases

● In order to reach this goal, HIV testing and antiretroviral (ARV) prophylaxis and treatment are essential

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PMTCT: More Than Just AntiretroviralsFour Pillar Prevention Strategy

• Pillar 1 Prevention of HIV in  Women• Pillar 2 Prevention of Unintended Pregnancies in HIV + Women

• Pillar 3 Prevention of MTCT from an HIV + Woman to her infant

• Pillar 4 Support for HIV+ Mother and Family

• Wilcher, R, et.al Sex Trans Inf 2008: 84 (Supp2):iii54‐60.

What is Needed to Prevent MTCT: The PMTCT Cascade

• What it really entails 

Credit: Lynne Mofenson MD NICHD

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Prevention Strategies in the US• Planned conception• Universal prenatal testing of all pregnant women• Use of combination antiretrovirals during pregnancy to reliably and durably suppress viral load 

• Individualized laboratory management (CD4 count and HIV viral load)

• Infant antiretroviral prophylaxis• Elective C‐section (Viral Load 

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Reproductive Health Care:Goals of Preconception Counseling

Improve the knowledge, attitudes and behaviors of men & women related to preconception health.

Assure all women of childbearing age in U.S. receive preconception care that will enable them to enter pregnancy in optimal health.Reduce risks indicated by previous pregnancy which can prevent or minimize problems for mother and her future children.Reduce the disparities in adverse pregnancy outcomes.

HIV Testing

Patients routinely tested for HIV should include: 

• All patients aged 13‐64 years

• All patients initiating treatment for TB

• All patients seeking treatment for STDs during each visit for a new complaint, regardless of specific behavioral risks for HIV infectionCDC. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in healthcare settings. MMWR 2006;55(RR14);1-17.

HIV TestingHIV testing should be: • Voluntary and with the patient's knowledge that HIV testing is planned

• Provided as an opt‐out healthcare  service• Accompanied with information, including an oral and/or written explanation of HIV infection and the meanings of positive and negative test results

• Consented for in the same way as other screening or diagnostic tests

• Declinations should be documented in the medical record.

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HIV Testing• Test all persons at high risk for HIV at least annually

– High risk populations include: MSM or heterosexual persons who have had more than one sex partner since their last HIV test, injection‐drug users, sex workers, and sexual partners of people at high risk or with a diagnosis of HIV

• For those at lower risk, repeat testing should be performed based on clinical judgment

• Encourage patients and their prospective partners to be tested before initiating a new sexual relationship

HIV Testing in Pregnancy

• Test women as early as possible during each pregnancy

• A second HIV test during the third trimester, preferably 

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HIV Testing in Labor and Delivery• Women with undocumented HIV status in labor should be screened with a rapid/expedited HIV test

• Women with unknown status after delivery should be screened immediately postpartum 

• If the rapid/expedited test is reactive, immediately initiate antiretroviral prophylaxis. Do not wait for the result of a confirmatory test.

Recommendations for 3rd Trimester Repeat HIV Testing

● In jurisdictions with an elevated incidence of HIV/AIDS among women

● Women known to be at high risk for HIV

● Facilities that identify HIV infection in at least 1/1,000 women screened

● Women who have signs or symptoms of acute HIV infection (acute retroviral syndrome)

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Why Aren’t All Pregnant Women Tested?

• Provider• Language barriers • Late entry or no prenatal

care • Patient perceived as not at

risk• Provider does not strongly

recommend testing to all women

• Patient• Women’s reasons for not

being tested– Do not think they are at

risk– Have been tested

“recently”– Test not offered or

recommended

• Negative consequences of testing rarely mentioned

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Case Study #1

• Lisa and her partner Joseph are expecting their first baby. Lisa is 11 weeks pregnant and this is her first visit. She reads a pamphlet in the waiting room.

• When you offer HIV testing to Lisa as part of her prenatal testing she tells you “I don’t need HIV testing. I haven’t been with anyone but Joseph and I don’t do drugs”

• How do you proceed?• If the case scenario changed and she accepted and said she tested negative, how would you proceed?

I’m HIV positive and pregnant…now what?

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Perinatal HIV Transmission● Without ARV drugs during pregnancy, risk of

transmission from mother to infant is 1 in 4● Pediatric AIDS Clinical Trials Group (PACTG) 076

found that by giving zidovudine (ZDV) to the pregnant woman during pregnancy, labor, and delivery, and to her newborn, transmission could be reduced to 8%

● The risk of perinatal transmission can now be less than 2% (1 in 50) with:● Highly effective ARV therapy (HAART)●Elective Cesarean section as appropriate ●Formula feeding

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Assuming No Interventions:

Reproductive Health Care:Preconception/Postconception Opportunities

(ACOG, 2006)• Optimize maternal HIV stability.• Choose “safe” ARV’s• Ed/Counsel HIV MTCT risks.• For HIV Discordant Couples discuss

optimal risk reduction techniques.• Evaluate need for vaccination/OI

prophylaxis.• Optimize Nutritional Health• PNV/Folic Acid.• Genetic Screening/Compile OB History.

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Timing of Perinatal HIV Transmission: Non-Breastfeeding Women

● Intrauterine (before 36 weeks) ~20% of cases● Virologic detection of HIV in newborn at 1–2 days of life

● Peripartum ~80% of cases● Onset of placental separation● Mother-to-fetus microtransfusions● Labor and rupture of membranes

● Most transmission occurs close to or during labor and delivery (L&D) 14

A Healthy Pregnancy: The Mother

HIV viral load monitoring • Initial visit • 2‐4 weeks after ART is started or changed• Monthly until HIV is undetectable• Every 3 months throughout pregnancy• At 34‐36 weeks gestation  HIV drug‐resistance testing with ART initiation and regimen changesCD4 monitoring every trimester Selecting, monitoring, and changing ART

Monitoring and PlanningMonitoring • Infant growth and development • Maternal complications

Plan for Labor & Delivery• Vaginal delivery recommended if HIV viral load 1,000 at 38 weeks• IV zidovudine (AZT) recommended (BIII) if HIV viral load >400• Avoid procedures that increase transmission risk:

– Rupture of membranes (natural or artificial) and labor onset– Fetal scalp electrodes – Forceps or vacuum extractor – Episiotomy 

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Factors Influencing Perinatal Transmission

● Maternal Factors●High HIV-1 RNA levels (viral load [VL])●Low CD4+ lymphocyte count (“T-cells”) ●Co-infections: Hepatitis C, cytomegalovirus

(CMV) bacterial vaginosis●Maternal injection drug use●No ARV therapy or prophylaxis

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Risk of MCT

• In studies prior to any therapy:– Africa: 30‐45%– US:     20‐25%– ECS:      13%

– What were the factors influencing the large differences in world wide MCT?

Risk of MCT

• Possible hypothesis:– Breast feeding– HIV strain differences– Immune status of mother– Co‐factors/Nutritional status– Genetic factors of the host

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Reproductive Health Care: Vertical Transmission Protocol

• All pregnant HIV + women should be offered ART to maximally suppress viral replication, reduce the risk of perinatal transmission and minimize the development of resistant virus.

• Start ART at least by 28 wks gestation.• Include AZT if possible.• Mother treated during pregnancy, IV AZT

antepartum and infant 6 wks after delivery.• Educate/counsel breast milk transmission.

Review: Goals of ARV Therapy

● Suppress HIV to below the limits of detection or as low as possible for as long as possible

● Prolong life and improve quality of life

● Preserve or restore immune function

● Reduce risk of perinatal transmission

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Resources for Clinicians

• Offering information on AIDS treatment, prevention, and research

• Clinical guidelines for ARV treatment– Perinatal/Mother-to-Child Transmission – Pediatrics– Adults and Adolescents

• http://www.aidsinfo.nih.gov107

Summary of Current Knowledge on Factors Affecting Mother-to-Child HIV-1 Transmission

Known risk factorsHigh maternal viral loadViral genotype/phenotypeAdvanced maternal HIV diseaseLow CD4 count or percentVaginal deliveryDuration of membrane rupture > 4 hoursPremature delivery (< 37 weeks)Breastfeeding

Factors for which evidence is suggestive but not conclusiveGenetic factorsImmature immune system in infantIncreased viral strain diversity Maternal neutralizing antibodyIllicit drug use during pregnancyFrequency of unprotected sexual intercourseMultiple sex partners during pregnancyMaternal nutritional statusAnemia during pregnancy Cigarette smoking ChorioamnionitisAbruptio placentaePlacental P. falciparum infestationSyphilis and other STDFetal scalp electrodesEpisiotomy and vaginal tears

The Infant: Preventing HIV infection

• Prevention of Mother to Child Transmission does not end at delivery

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Perinatal ARV Guidelines

• USPHS Task Force Recommendations for the Use of ARV Drugs in Pregnant HIV-1 Infected Women for Maternal Health and to Reduce Perinatal HIV-1 Transmission in the United States

• Developed in 1994 in response to PACTG 076• Working group meets monthly• Updated recommendations available online at

AIDSInfo website (http://www.aidsinfo.nih.gov)42

PREVENTION OF MCT

• Starting therapy at birth still reduces the risk of transmission of HIV, from 20%  to 13‐15%.

• Therefore, women with no PNC, or no HIV testing on file, should be offered rapid HIV testing at presentation in active labor.

CARE OF THE HIV‐EXPOSED INFANT

• At birth, begin ZDV therapy, based on weight and gestational age: for full term infants: 2mg/kg/dose 4x/day or 4mg/kg 2x/day

• If high risk: if there was no maternal treatmentmaternal VL >1000PROM >8‐12hrsprematurity 

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CARE OF THE HIV‐EXPOSED INFANT

• If high risk: no maternal treatmentNICHD‐PACTG 1043Enrolled newborns when  mom presented in labor on no 

therapy:

Infant regimens/infection rate (including in‐utero)ZDV for 6 weeks  11%ZDV and NVP 3doses/72hrs 7.1%ZDV and 3TC/Nelfinavir for 2 weeks 7.4%

RISKS OF PERINATAL ANTIRETROVIRAL THERAPY

• Blanche, et al. French Collaborative Study:Initial report of 2 deaths, related mitochondrial disease in HIV‐exposed uninfected infants. (perinatal rx with ZDV/3TC).Later, report of possibly 8 children with less severe symptoms.

• US meta‐analysis of >23,000 HIV‐exposed infants revealed no unexpected events

CARE OF THE HIV‐EXPOSED INFANT

Testing for the diagnosis:• Use RNA qualitative assay

» False positive rate  1‐2%» False negative rate 4% after 2 weeks of age

– If mother is known to be HIV +, and infant at low risk:

• PCR RNA at 2 weeks, 4wks and 4mon • A negative RNA ql assay at 2 wks and 4wks months indicates infant is presumptively HIV negative. A negative at 4months r/o HIV infection (as per CDC)

• For high risk infants, additional tests at day 1 of life and at 8 weeks of age (along with tests at 2wks,4wks and 4months)

• Follow HIV ab until infant becomes HIV ab negative, usually between 12 and 18 months of age.

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CARE OF THE HIV‐EXPOSED INFANT

• At birth, begin ZDV therapy, based on weight and gestational age.

• Continue ZDV for 6 weeks.• At 2 weeks, assess CBC, send HIV PCR QL• At 4 wks send CBC, CD4, HIV PCR• At 6 weeks,d/c ZDV and start TMP/SMZ if there is only one RNA test results available. If there are 2 neg(2 and 4wks), do NOT need to start TMP/SMZ

CARE OF THE HIV‐EXPOSED INFANT

Testing for the diagnosis:• Use RNA qualitative assay

» False positive rate  1‐2%» False negative rate 4% after 2 weeks of age

– If mother is known to be HIV +, and infant at low risk:• PCR RNA at 2 weeks, 4wks and 4mon • A negative RNA qualitative assay at 2 wks and 4wks months indicates infant is presumptively HIV negative. A negative at 4months r/o HIV infection (as per CDC)

• For high risk infants, additional tests at day 1 of life and at 8 weeks of age (along with tests at 2wks,4wks and 4months)

• Follow HIV ab until infant becomes HIV ab negative, usually between 12 and 18 months of age.

Breastfeeding by HIV‐infected women is not recommended in the United 

States.• Breastfeeding by HIV‐infected women (including those receiving ARV drugs) is not recommended in the United States where replacement feeding is affordable, feasible, acceptable, sustainable, and safe and the risk of infant mortality due to diarrheal and respiratory infections is low.

• Importantly, although significantly lowering the risk of postnatal infection, neither infant nor maternal postpartum ARV prophylaxis completely eliminates the risk of HIV transmission through breast milk.

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Mixed feeding (breast + formula) is most dangerous.

• Mixed feeding is the most dangerous method– Formula feeding can irritate the lining of the baby's stomach

– Irritation makes it easier for the HIV in breast milk to get in and cause an infection. 

– In a South African study of HIV‐positive women and their babies, 36 percent of babies who received mixed feeding were reported infected compared to about 25 percent of those who were exclusively breast‐fed and 19.5 percent of formula‐fed babies. 

HIV-Positive Pregnant Women:Psychosocial Issues

● Stigma: in community and in health care ● Non-disclosure: to partners, health-care team● Domestic partner violence● Mental health ● Substance abuse● Worry about infection status of infant● For more information, see http://www.aidsetc.org

or http://www.womenchildrenhiv.org102

Legal and Ethical Issues with Impact on HIV Care

● Confidentiality and HIV reporting● Non-disclosure to sexual partners● Reproductive health and family planning● Immigration issues● Access to prenatal/HIV care● For more information see: http://www.aidsetc.org

and search on the topic of interest

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Perinatal Hotline – National Perinatal HIV Consultation and Referral Service

• Around-the-clock advice on testing and care of HIV-infected pregnant women and their infants

• Provides referral to HIV specialists and regional resources– 1-888-448-8765

– HIVtesting@nccc.ucsf.edu

• For additional resources: http://www.nccc.ucsf.edu

Remaining Research Questions

• Long term outcome of perinatal exposure to HAART (p219, SMAART)

• Benefits of initiating treatment for infected neonates at 2 wks vs 1 or 3 months of age

• Optimal treatment for HIV‐exposed neonates with no maternal pre‐treatment

Case Study #2

• Linda is a 24 year old female who presents to L&D in active labor and delivers precipitously. She has never had and HIV test. She admits to active intravenous drug use. What other questions do you want to ask her?

• What intervention would you recommend for her baby who was full term by dates

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Case Study #3

• Shantay is a 30 year old woman who presents to the perinatal clinic. She is 30 weeks pregnant. When you ask her if she has had prenatal care, She tells you no. “this is my 4th child and I know what I am doing“. She tests HIV positive at this visit. What do you do next?

• She delivers a healthy baby girl at 38 weeks. Shantay’sviral load is undetectable and her CD4 count is 550. What do you offer her next? What do you offer for the baby?

• Shantay tells you she wants to breastfeed. How do you counsel her?

We are Citizens of the World

HIV Global Burden

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End PMTCT by 2015

Mississippi to Milan

• Mississippi baby• Milan Baby• Aggressive treatment• Thought to be cured….then a relapse.

Challenges: What’s Left to Do

• Challenges:– Maintaining momentum costs money and utilizes many resources

– Building into the Standard of Care

– Gaining “buy in” worldwide

– Public health and provider education

• Opportunity to use PMTCT to:– Address other health threats

– Address maternal and child mortality

– Strengthen MCH services– Ensure good health outcomes for mother, child and family

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Special Thanks to:

CHOP Family Care Center and Medical Director‐Dr. Rick RutsteinPennsylvania AIDS Education and Training CenterDr. Lynne Mofenson, NICHDDr. Kathleen Brady (Upenn/Philadelphia Department of Health)