HIV Case Conference
Working Toward Elimination of Mother-to-Child Transmission:
Practical Aspects for the Perinatal Team
Carina Rodriguez, MD
Faculty, Florida/Caribbean AETC
University of South Florida
Thursday, May 8, 2014
Time: 2:00 pm-3:00 pm (EDT)
HIV Case Conference
Series Objectives
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Identify the role, uses, and complications of antiretroviral therapy as a
treatment option according to the Department of Health and Human
Services
Describe the major issues of age and gender appropriate HIV care
including management of special populations such as pregnant women,
and gay, lesbian or transgender patients
Identify and treat HIV disease, HIV complications and co-morbid conditions
in the primary care setting
Identify and access resources and standard of care protocols that can be
immediately applied to any clinical setting
Describe legislation and/or recommendations about HIV testing,
confidentiality, access to medical care, post-exposure prophylaxis and preexposure prophylaxis
Identify the modes of transmission of HIV and epidemiology of the disease
and related infections
Discuss strategies to increase the ability of healthcare providers to provide
culturally competent care
Session Specific Objectives
Upon completion of this program, participants will be
able to:
• Review current recommendations for the prevention of motherto-child transmission
• Learn virologic and serologic methods for identification of HIV
infection, their use in pregnancy and special scenarios, including
discordant partners, suspected acute infection and infant testing
• Review current evidence regarding mode of delivery and risk for
infection
• Learn current antiretroviral therapies for HIV-infected pregnant
women and exposed/infected children
• Recognize clinical scenarios associated with increased risk for
transmission and selective antiretroviral therapy/prophylaxis
Continuing Education
Disclosure
• The following presenter has financial relationships
with the following commercial entities to disclose:
o Carina Rodriguez, MD
• Grant/Research Support: Gilead, ViiV, Merck, and
NICHD
• This presenter will not discuss any off-label use
or investigational product during the program.
Continuing Education
(Up to 1.0 hours of CE/CME)
Continuing Medical Education
Continuing Education
This activity has been planned and
implemented in accordance with the Essentials
Areas and Policies of the Accreditation Council
for Continuing Medical Education through the
joint sponsorship of the Florida AHEC Network
and the Florida/Caribbean AIDS Education and
Training Center. The Florida AHEC Network is
accredited by the Florida Medical Association to
provide continuing medical education for
physicians.
Suwannee River Area Health Education Center,
Inc., is a Florida Board of Nursing, Clinical
Social Work, Marriage, Family Therapy, Mental
Health Counseling, Dentistry, and Pharmacy
approved provider of continuing education. CE
Broker Provider ID #50-1922. This program
meets the requirements for up to 5.0 contact
hours.
The Florida AHEC Network designates this live
activity for a maximum of 5.0 AMA PRA
Category 1 Credits™. Each physician should
claim only the credit commensurate with the
extent of their participation in the activity.
For questions regarding CE or CME, please
contact our Professional Education Manager at
ce@srahec.org or 386-462-1551.
Perinatal guidelines
March 2014
Updates in terminology
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The terms “mother-to-child transmission (MTCT)” and “prevention of
mother-to-child transmission (PMTCT)” have been replaced with “perinatal
transmission” and “prevention of perinatal transmission”
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Slides are based on most recent recommendations by the Department of
Health and Human Services (HHS)
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Can be accessed at http://aidsinfo.nih.gov/guidelines/html/3/perinatalguidelines
Rating Scheme for
Recommendations
Milestones in Perinatal HIV
 Pediatric AIDS Clinical Trials Group 076
 Major Achievement in HIV research
 Showed administration of zidovudine (ZDV) to
pregnant women and their infants could reduce
perinatal transmission by 70%
 Increased HIV testing in pregnancy and
combination ARV prophylaxis during pregnancy
has reduced perinatal transmission to <2%.
 Every HIV-infected infant is a sentinel event
representing missed opportunities.
Perinatal HIV/AIDS Cases
Perinatal Transmission
• Perinatal HIV transmission is the most
common route of HIV transmission in
children.
• Since the beginning of the epidemic, 9522
cases of AIDS have been reported
perinatally – 4986 of those have died.
• HIV perinatal transmission peaked in 1991
to 1650 perinatally infected infants – there
were 162 perinatally infected infants in 2010
HIV-Infected Newborns
HIV-Infected Infants 2013
HIV-Infected Infants 2014
Common risk factors seen in
HIV infected infants
• Maternal Substance Use
• Late, Minimal or NO Prenatal care
• Maternal Denial (or Ignoring) their Known
HIV diagnosis – refusing HIV testing in
pregnancy warrants further
investigation/discussion
• Maternal Mental Health issues
• Maternal HIV diagnosis at Labor and
Delivery
Case 1
• 23 y/o female with no history of prenatal care presents in
labor at outlying hospital
• Rapid HIV testing done and negative
• Normal SVD, no complications
• 2 months later, mom is admitted to substance abuse
rehabilitation facility and HIV testing is repeated and
positive
• Pediatrician is contacted and performs HIV ELISA that is
positive
• PCP contacts DOH for further advice
• Infant DNA PCR and RNA PCRs confirm HIV infection
• Could this infection have been prevented?
Awareness of Serostatus
Estimates of Transmission
25%
Unaware of
diagnosis
54% of new
infections
People living
with
HIV / AIDS
1,039,000 –
1,185,000.
New sexual
infections each
year
~32,000
75% aware
of diagnosis
46% of new
infections
Marks G et al.
AIDS 2006, 20:1447 – 1450.
HIV Infection Before ART
HIV Testing in Acute Infection
Intrapartum Care
Transmission and Mode of
Delivery
 Scheduled cesarean delivery at 38 weeks
gestation to minimize perinatal HIV transmission
for women with HIV RNA levels >1000 copies/ml
or unknown levels near the time of delivery. (AII)
 Perform cesarean irrespective of administration
of antepartum ARV drugs
 IV ZDV should be administered for 3 hours total
prior to scheduled delivery
 Cesarean sections performed for standard obstetrical
indications should be scheduled for 39 weeks gestation
Intrapartum Care
Intrapartum Care- Unknown HIV
status
 Conduct rapid HIV antibody testing for women in
labor with unknown HIV status. (AII)
oIf positive:
Perform confirmatory testing ASAP
Administer maternal IV ZDV and infant
combination prophylaxis pending results of
confirmatory test. (AII)
Continue infant prophylaxis for 6 weeks if
confirmatory tests are positive (AI); discontinue
prophylaxis if confirmatory testing is negative
Acute HIV infection
• When acute retroviral syndrome is suspected in pregnancy or during
breastfeeding, a plasma HIV RNA test should be obtained in
conjunction with an HIV antibody test (AII).
• Repeat HIV antibody testing in the third trimester is recommended for
pregnant women with initial negative HIV antibody tests who are known
to be at risk of acquiring HIV, are receiving care in facilities that have an
HIV incidence in pregnant women of at least 1 per 1,000 per year, are
incarcerated, or who reside in jurisdictions with elevated HIV incidence
(AII).
• All pregnant women with acute or recent HIV infection should start a
combination ARV regimen ASAP (AI).
Hidden in the Data
• Of the 136 Infected babies born in Florida from 20002005:
 27% of all mothers who delivered an infected infant did
not know they were positive prior to delivery.
 20% of all mothers who delivered an infected infant
contracted HIV during the pregnancy.
Case 2
HIV Care Continuum
Model of Demonstration
MMWR 2011
Florida Statutes: HIV Testing
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Written informed consent is no longer required prior to HIV screening in health
care settings (See Exceptions), however the provider needs to document in the
medical record (MR) that patient provided verbal consent.
Prior to ordering an HIV test, medical providers are required to:
o Inform patients that an HIV test will be performed
o Provide information about the test
o Advise the patient of their right to decline the HIV test
o Document in MR that patient provided verbal consent
Exceptions when written consent is required:
o Blood donation
o HIV testing for insurance or contract purposes
Refusal for HIV testing during pregnancy needs to be in writing (testing in
pregnancy is through opt-out process on first trimester and 28-32 weeks)
Minors can be tested for HIV without parental consent provided the minor gives
informed consent
Recommendations for Initiating ART:
CD4 Count or Clinical Category
Recommended for all CD4 counts:
• CD4 count <350 cells/µL (AI)
• CD4 count 350-500 cells/µL (AII)
• CD4 count >500 cells/µL (BIII)
Recommended regardless of CD4 count:
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Pregnancy (AI)
History of AIDS-defining illness (AI)
HIV-associated nephropathy (HIVAN) (AII)
Hepatitis B (HBV) coinfection (AII)
Age >50 years (BIII)
HIV cycle
Antiretroviral Drugs
Preferred ARV regimens
in Pregnancy
NRTI backbone
• ZDV/3TC
• TDF/FTC
• ABC/3TC
PI based
• ATV/r
• LPV/r
II based
• RAL
NNRTI based
• EFV (start after 8 weeks)
ARV prophylaxis in pregnancy
Recommendations for Use of Antiretroviral Drugs
during Pregnancy
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Preferred NRTIs for ARV-naive pregnant women have been expanded to
include abacavir plus lamivudine and tenofovir plus emtricitabine or
lamivudine in addition to zidovudine plus lamivudine.
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Preferred protease inhibitors (PIs) for ARV-naive pregnant women remain
ritonavir-boosted atazanavir and ritonavir-boosted lopinavir.
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Alternative PIs include ritonavir-boosted darunavir and ritonavir-boosted
saquinavir.
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Preferred NNRTI for ARV-naive pregnant women is efavirenz, initiated after
the first 8 weeks of pregnancy.
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Nevirapine is the alternative NNRTI for ARV-naive pregnant women.
Recommendations for Use of Antiretroviral Drugs
during Pregnancy
• Raltegravir has been moved to the Alternative category for ARVnaive pregnant women, for consideration particularly when drug
interactions with PI -based regimens are a concern.
• In addition, some experts may use raltegravir in late pregnancy in
women with high viral load
• There is insufficient data during pregnancy for dolutegravir,
elvitegravir/cobicistat/tenofovir/emtricitabine fixed drug combination,
ritonavir-boosted fosamprenavir, maraviroc, and rilpivirine.
Adjusted Rate Ratios for Transmission
of HIV in Discordant Couples
Quinn TC et al. NEJM 1996;335:1621-1629.
^ Viral load in blood may not be predictive of genital tract viral load
Reproductive Options for HIVConcordant and Serodiscordant Couples
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HIV-infected partner(s) in HIV-seroconcordant and HIV-serodiscordant
couples planning pregnancy attain maximum viral suppression before
attempting conception (AIII).
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Periconception administration of ARV pre-exposure prophylaxis (PrEP) for
HIV-uninfected partners may offer an additional tool to reduce the risk of
sexual transmission (CIII)
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Tenofovir disaproxil fumarate/emtricitabine– approved in July 2012 for HIV
prevention in individuals at high risk of HIV transmission
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Pregnancy is not a contraindication to PrEP.
 Postpartum
Follow-Up of HIVInfected Women
◦ Decisions about continuing cART after delivery should
be made in consultation with a woman and her HIV
provider, ideally before delivery (AIII).
◦ cART is currently recommended for all HIV-infected
individuals to reduce the risk of disease progression
and to prevent HIV sexual transmission. Strength and
evidence vary by pretreatment CD4 cell count.
Infant Antiretroviral Prophylaxis
 All HIV-exposed infants should receive a 6 week course of ZDV
prophylaxis (AI)
 Mother received standard antepartum and intrapartum ARV
prophylaxis with suppressed HIV RNA: infant zidovudine alone
 Mother did not receive optimal antepartum and intrapartum
prophylaxis, risk of HIV transmission is higher, and additional infant
ARVs may be recommended
 Infants born to mothers who did not receive antepartum ARV drugs
 6 week course of ZDV, plus
 3 doses of NVP in the first week of life (AI)
 1st dose at birth
 2nd dose 48 hours later
 3rd dose 96 hours after second dose
o
(Begin regimen as soon as possible post delivery)
Infant Antiretroviral Prophylaxis
• Infant Zidovudine HIV Prophylaxis Dosing
Age
Dose
Duration
≥35 weeks gestation at birth
4 mg/kg/dose PO twice daily
If unable to tolerate oral agents:
3 mg/kg/dose IV every 12 hours
Birth through 6 weeks
≥30 to <35 weeks gestation
2mg/kg/dose PO or 1.5
mg/kg/dose IV every 12 hours.
At age 15 days, increase to 3
mg/kg/dose PO or 2.3 mg/kg/dose
IV every 12 hours.
<30 weeks gestation
2 mg/kg/dose PO or 1.5
mg/kg/dose IV every 12 hours
At age 4 weeks, increase to 3
mg/kg/dose PO or 2.3 mg/kg/dose
IV every 12 hours
Give first dose as close
to the time of birth as
possible (preferably
within 6 to 12 hours)
Infant Antiretroviral Prophylaxis
Infant Nevirapine HIV Prophylaxis Dosing in addition to
ZDV for high risk cases, consult expert in pediatric HIV
Initial Postnatal Management of
the HIV-Exposed Neonate

Virologic tests should be performed at (AII)
 14-21 days,
 1 (to 2 months), and
 4 to 6 months
 Virologic tests at birth may be performed
 If mother did not have good virologic control during pregnancy
 If adequate follow-up can not be assured
 If infant received expanded prophylaxis, repeat PCR testing recommended
2-4 weeks after discontinuation
o * With two negative testing by 4 to 6 weeks, do not need to initiate
Pneumocystis jiroveci prophylaxis
Infant Antiretroviral Prophylaxis
• Alternative combination ARV prophylaxis regimens in
infants should be made in consultation with a pediatric
HIV specialist before delivery, if possible.
• A 4-week neonatal ZDV chemoprophylaxis regimen can
be considered when the mother has received standard
cART with consistent viral suppression and there are no
concerns related to maternal adherence (BII).
Diagnostic Testing in Infants
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Presumptive rule-out of HIV infection
o 2 or more negative virologic tests
 One at age ≥14 days and one at ≥1 month; or
 One negative virologic test at ≥2 months; or
 One negative HIV antibody test ≥6 months
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Definitive rule-out of HIV infection
o 2 or more negative virologic tests
 One at ≥1 month; and
 One negative virologic test at ≥4 months; or
 2 negative HIV antibody tests ≥6 months
Diagnosis of HIV infection
o 2 positive HIV virologic tests (NAAT-HIV-1 DNA or RNA)
on separate blood samples (regardless of age)
o Positive HIV antibody test with confirmatory
o Western blot (or IFA) at age ≥18 months
Strategies for HIV Care
Functional
Cure
Latent
reservoir
HIV
replication
in tissues
HIV replication
Latent
reservLLL;l;oir
Latent
reservoir
HAART
optimization
(Mega-HAART?)
HAART
HAART
during
acute
infection
Reactivation
strategy (HDACi,
PD-1) and
elimination of
reservoir cells
(vaccine,
Immunotherapy)
Viral reservoirs and their relative
contribution to plasma viremia
Stevenson, M.
Nature Medicine 9, 853 - 860 (2003)
HIV Cure
• 2011 - Berlin patient – Evidence of cure of HIV following
Bone Marrow Transplantation (Two transplants with
CCR5 Delta 32 mutation donor)
• 2013 - Mississippi Child – Evidence of functional cure of
HIV following treatment for HIV within 30 hours of life.
• 2014 - 2nd Infant with HIV seroreversion – treated
aggressively within 4 hours of life – remains on
antiretrovirals.
• Clinical trials are planned to address whether
administration of a three-drug regimen in therapeutic
doses to HIV-exposed high-risk infants could alter the
establishment and long-term persistence of HIV infection.
Unique aspects of HIV
infection in pediatrics
• Unique immunologic characteristics (evolving
immunity and immune tolerance)
• Unique “gut” immunity (relative lack of immune
activation in the gut and increased regenerative
capacity)
• Timing and source of infection more easily
determined than in adults
• Potential limitation of HIV infection prior to
establishment of latent reservoirs with early
treatment
Tobin, N. Curr HIV/AIDS Rep 2014
Summary
• Current guidelines provide excellent recommendations
for the prevention of perinatal HIV transmission
• There are many obstacles to effectively instituting the
appropriate interventions for prevention in all scenarios
for HIV + pregnant women
• Utilizing the guidelines and initiating appropriate
interventions at every opportunity for prevention of
perinatal HIV transmission is the only way we can get to
“ZERO”