PREVENTION OF MATERNAL TO
CHILD TRANSMISSION OF HIV-
RECENT ADVANCES
10/10/2019 1
HIV EPIDEMIC
• 2.2 million new infections occur each year
• It is estimated that 5 million children and
young people are currently living with HIV
• 80% of those children and youth live in only
20 countries, the majority located in Eastern
and Southern Africa.
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Global strategy to
promote an AIDS-Free Generation
• Prevent mother-to-child transmission of HIV.
• Provide pediatric HIV care and treatment.
• Prevent infection among adolescents and
young people.
• Protect and support children affected by HIV
and AIDS.
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• This strategy outlines two major goals to be
achieved by 2015:
• Eliminate new HIV infections in children.
• Reduce new infections among young people by
30%.
• The elimination of mother-to-child
transmission of HIV is key to helping reach
MDG 4 (Reduce Child Mortality), 5 (Improve
Maternal Health), and 6 (Combat HIV/ AIDS).
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HIV in CHILDREN
• Worldwide, > 700 children are newly infected with
human immunodeficiency virus (HIV) each day.
• The primary mode of HIV acquisition is through
mother to-child transmission (MTCT) during
pregnancy, childbirth, or breastfeeding.
10/10/2019 5
HIV in CHILDREN
• Without access to antiretroviral therapy, one-third of
these children will die by 1 year of age, and one-half
by age 2 years.
• In well-resourced health care systems, universal HIV
testing for pregnant women, provision of
antiretroviral therapy or prophylaxis, elective
caesarean delivery, and avoidance of breastfeeding
has reduced MTCT of HIV infection to 1%–2%.
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HIV Prevention
• Three key HIV prevention tools:
-Antiretroviral treatment of HIV-positive persons
-Prevention of mother-to-child transmission of HIV
-Voluntary medical male circumcision
• When used with HIV testing and counselling,
condoms, and other appropriately targeted
prevention activities, these put us on a plausible path
for eliminating new HIV infections.
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Strategic Approach
to Prevention of Pediatric HIV Infection
WHO
• Prevention of HIV infection among young persons
and pregnant women
• Prevention of unintended pregnancies in HIV-
infected women
• Prevention of HIV transmission from HIV-infected
women to their infants
• Provision of treatment, care, and support to HIV-
infected women and their families
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Why PMTCT?
• Preventing new HIV infections among children and keeping
their mothers alive is not only a moral imperative, it is also
one of the best investments the world can make to address
AIDS.
• Through comprehensive PMTCT programs, we not only keep
mothers and babies alive and healthy, we also support
healthier and more productive families and communities.
• Moreover, when a pregnant woman living with HIV enters the
health care system, it provides an opportunity to link the rest
of her family with highly effective interventions, such as HTC,
VMMC, family planning services and other health services.
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WHO guidelines- 2013
• Since 2010, new technologies, including CD4 testing , allow HIV testing
and treatment monitoring to be diversified and decentralized.
• Simple, safer, once-daily, single-pill ARV regimens that are suitable for
use in most populations and age groups have become more affordable and
more widely available in low- and middle-income countries.
• Countries are moving towards earlier initiation of triple-drug regimens
and simplified programming for the prevention of mother-to-child
transmission of HIV (PMTCT) that emphasizes the long-term health of
mothers living with HIV and preventing HIV infection among their children.
• The broader HIV prevention benefits of ARV drugs are being recognized:
in addition to improving health and prolonging lives, ART prevents the
sexual transmission of HIV.
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WHO guidelines-2013
• Promote expanded eligibility for ART with a CD4 < 500 cells/mm3
for adults, adolescents and older children: ( Priority -severe or
advanced HIV disease and CD4 count < 350 cells/mm3).
• ART is recommended to be initiated regardless of CD4 count for
certain populations-active TB+HIV, HIV + HBV infection OR severe
chronic liver disease, HIV-positive partners in serodiscordant
couples, pregnant and breastfeeding women and children<5y
age.
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Pregnant women -PMTCT
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Percentage of pregnant women with HIV
receiving ART for PMTCT
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2013 Consolidated ARV Guidelines
HIV/AIDS
DEPARTMENT
Treatment Recommendations
for Pregnant and
Breastfeeding Women:
Critical Issues
Objectives of Presentation
o Background
o Overview of Key Recommendations:
• When to Start ART
• Breastfeeding
• What ART to Start
o Issues and challenges
Introduction
• HIV is a family infection
• Parents have an impact on transmission of HIV
to the baby
• There is increased chance of transmission to
the baby when a woman becomes infected
with HIV when she is pregnant or
breastfeeding
16
Pregnancy Outcome: Goals
• Uncomplicated pregnancy
• Healthy, uninfected infant
• Healthy mother who has not compromised
her future options for HIV therapy
17
Estimated Risk of MTCT
(Adapted from De Cock KM et al, 2000)
Transmission Rate
Without Any
Timing Interventions
During pregnancy 5-10%
During labor and delivery 10-15%
During breastfeeding 5-20%
Overall without breastfeeding 15-25%
Overall with breastfeeding to six months 20-35%
Overall with breastfeeding to 18-24 months 30-45%
Note: Rates vary because of differences in population characteristics such as maternal
CD4+ cell counts, RNA viral load and duration of breastfeeding.
“HIV transmission through breastfeeding: A review of available evidence.” Marie Louise
Newell; endorsed by UNICEF, UNFPA, WHO, UNAIDS. 2004 (adapted from De Cock
KM et al., 2000). 18
Of 100 Babies Born to HIV Infected
Mothers Not on Treatment
11 infected during breastfeeding
17 infected
during birth
67 not
infected*
5 infected
in utero
*without treatment for parents, most will be orphaned
19
Factors Influencing MTCT
• Viral Load
– The higher the viral load, the higher the risk of
MTCT
• Lower risk through:
– Use of ART during pregnancy and postpartum to
mother and newborn
– Adequate nutrition, particularly vitamin A
20
Factors Influencing MTCT
• Maternal factors increasing risk:
– Viral or parasitic placental infection (especially
malaria)
– Becoming infected with HIV during pregnancy
– Severe immune deficiency
– Advanced clinical and immunological state
– Maternal malnutrition
21
Factors Influencing MTCT
• Labor and delivery factors increasing risk:
– Prolonged rupture of membranes (>4 hours)
– Injury to birth canal during child birth
– Antepartum procedures
– Acute chorioamnionitis
– Invasive fetal monitoring
– Instrumental delivery
– Mixing of maternal and fetal body fluids
– Routine infant airway suctioning
22
Factors Influencing MTCT
• Fetal Conditions increasing risk:
– Premature delivery
– Low birth weight
– Immature immune status
– First infant in a multiple birth
23
Antenatal Care
• Primary prevention during pregnancy
– Education about safer sex with use of condoms for
mother and father
– Early treatment of STIs
– Safer sex during pregnancy and lactation
• Offer VCT to all pregnant women
• Antenatal visits are vital opportunities for
PMTCT for both HIV-positive and HIV-negative
women
24
Progress and Barriers
o Limited coverage and implementation of PMTCT
and ART for pregnant women in many high
burden countries Steady progress reducing infant infections
• 65% PMTCT ARV coverage New child HIV infections, low and middle
• Limited ART in those eligible for treatment 600 income countries (thousands)
• High loss to follow-up along PMTCT cascade 500
• Low ARV coverage during breastfeeding 400
300
o Complexity of Option A 200
• Different treatment and prophylaxis regimens 100
through pregnancy and breastfeeding 0
•
2000 2005 2010 2015
Difficulty of long-term NVP dosing for infants
•2009: ~430,000 infant infections
• Requirement for CD4 to determine eligibility •2012: ~290,000 infant infections
• Follow up along the PMTCT cascade is very low •2015: Global Plan target <40,000
o Current approach needs to be optimized to achieve
universal access and elimination
Evolution of WHO PMTCT ARV
Recommendations
2001 2004 2006 2010 Launch
Jun 2013
4 weeks AZT; AZT from 28 AZT from 28wks Option A Option B or B+
AZT+ 3TC, or wks + sdNVP + sdNVP (AZT +infant NVP) Moving to ART
sdNVP +AZT/3TC 7days Option B for all PW/BF
PMTCT
(triple ARVs-for (TLE)
own health-ZLN + Infant NVP
Move towards: more effective ARV drugs, or TLE; else /AZT bd x 6w
extending coverage throughout MTCT risk ZL+Lpv/r /ABC or
period, and ART for the mother’s health /TLE;)
No
ART
CD4 <200 CD4 <200 CD4 <350 CD4 <500
recommendation
When to Start ART
Summary of Changes in Recommendations:
When to Start in Adults
TARGET STRENGTH OF
POPULATION 2010 ART GUIDELINES 2013 ART GUIDELINES RECOMMENDATION &
(ARV-NAIVE) QUALITY OF EVIDENCE
HIV+ ASYMPTOMATIC CD4 ≤500 cells/mm3 (CD4 Strong, moderate-quality
CD4 ≤350 cells/mm3 ≤ 350 cells/mm3 as a evidence
priority)
HIV+ SYMPTOMATIC Strong, moderate-quality
WHO clinical stage 3 or 4
No change evidence
regardless of CD4 cell count
PREGNANT AND Strong, moderate-quality
BREASTFEEDING CD4 ≤350 cells/mm3 Regardless of CD4 cell count
evidence
WOMEN WITH HIV or or WHO clinical stage
WHO clinical stage 3 or 4
HIV/TB CO-INFECTION Presence of active TB disease, Strong, low-quality evidence
No change
regardless of CD4 cell count
Evidence of chronic active HBV Evidence of severe chronic
HIV/HBV CO- Strong, low-quality evidence
disease, regardless of CD4 cell HBV liver disease,
INFECTION count regardless of CD4 cell count
HIV+ PARTNERS IN
Regardless of CD4 cell
SERODISCORDANT Strong, high-quality evidence
No recommendation established count or WHO clinical stage
COUPLE
RELATIONSHIP(S)
Recommendations
“Option B+” “Option B”
All pregnant and breastfeeding women infected with HIV should initiate triple ARVs (ART),
which should be maintained at least for the duration of mother-to-child transmission risk.
Women meeting treatment eligibility criteria should continue lifelong ART .
(strong recommendation, moderate-quality evidence)
For programmatic and operational In some countries, for women who
reasons, particularly in generalized are not eligible for ART for their own
epidemics, all pregnant and health, consideration can be given to
breastfeeding women infected with stopping the ARV regimen after the
HIV should initiate ART as lifelong period of mother-to-child
treatment. transmission risk has ceased.
(conditional recommendation, low- (conditional recommendation, low-
quality evidence) quality evidence)
Algorithms
“Option B+” “Option B”
TLE
Rationale: Shift from Option A to B+ or B
BENEFITS FOR MOTHER AND CHILD BENEFITS FOR PROGRAM DELIVERY &
PUBLIC HEALTH
Ensures all ART eligible women initiate Reduction in number of steps along PMTCT
treatment cascade
Prevents MTCT in future pregnancies Same regimen for all adults (including
pregnant women)
Potential health benefits of early ART for Simplification of services for all adults
non-eligible women
Reduces potential risks from treatment Simplification of messaging
interruption
Improves adherence with once daily, single Protects against transmission in discordant
pill regimen couples
Reduces sexual transmission of HIV Cost effective
Major issue now is not “when to start” or “what to start” but “whether to stop”
Programmatic considerations for B+
• Operational and programmatic advantages to lifelong ART for
pregnant and breastfeeding women (“B+”), particularly in settings
with:
– Generalized epidemics
– High fertility (though need to strengthen FP)
– Long duration of breastfeeding
– Limited access to CD4 to determine ART eligibility
– High partner serodiscordance rates
• National programmes need to decide B or B+
ARVs and breastfeeding
2013 (no change from 2010)
National agencies should decide between promoting mothers with HIV to either
breastfeed and receive ARV interventions or to avoid all breastfeeding
Where the national choice is to promote BF, mothers whose infants are HIV
uninfected or of unknown HIV status should:
• exclusively breastfeed their infants for the first six months of life
• introduce appropriate complementary foods thereafter, and continue
breastfeeding for the first 12 months of life
• breastfeeding should then only stop once a nutritionally adequate and safe diet
without breast-milk can be provided
(strong recommendation, high-quality evidence for the first 6 months;
low-quality evidence for the recommendation of 12 months)
WHAT ART REGIMEN TO START
Summary of Changes in Recommendations:
What to Start in Adults
FIRST-LINE REGIMENS (PREFERRED ARV REGIMENS)
STRENGTH &
TARGET
2010 ART GUIDELINES 2013 ART GUIDELINES QUALITY OF
POPULATION EVIDENCE
AZT or TDF + 3TC (or
HIV+ ARV-NAIVE
FTC) + EFV or NVP
ADULTS
(ZLN / TLE)
HIV+ ARV-NAIVE
AZT + 3TC + NVP or TDF + 3TC (or FTC) + EFV Strong,
PREGNANT
EFV (ZLN/E) (as fixed-dose combination) moderate-quality
WOMEN
(TLE) evidence
HIV/TB AZT or TDF + 3TC (or
CO-INFECTION FTC) + EFV (ZLE/TLE)
HIV/HBV TDF + 3TC (or FTC) +
CO-INFECTION EFV (TLE)
Evidence Summary: Safety of EFV and TDF
in Pregnancy
EFV TDF
No increased risk of birth defects with
EFV when compared with other ARVs
o Potential concerns include renal toxicity,
adverse birth outcomes and effects on
bone density
o Systematic review assessed the toxicity of
fetal exposure to TDF in pregnancy
• In Antiretroviral Pregnancy Registry,
prevalence of all birth defects with
TDF exposure in 1st trimester was
2.4% (same as background)
o Limited studies showed no difference in
o Systematic review (including Antiretroviral fetal growth between exposed/unexposed
Pregnancy Registry), reported outcomes o No studies of TDF among lactating
for 1502 live births to women receiving women, who normally have bone loss
EFV in the first trimester and found no during breastfeeding
increase in overall birth defects o Current data reassuring
o More extensive studies ongoing
Source: Ford N et al. AIDS, 2011. Ford N et al. AIDS, 2013. Ekouevi DK et al.J AIDS, 2011. WHO, Geneva Use of EFV during pregnancy. 2012.
http://www.who.int/hiv/pub/treatment2/efavirenz/en
Nightingale SL. JAMA, 1998. British HIV Association. Guidelines for the management of HIV infection in pregnant women. HIV Medicine. 2012. De Santis M et al. Arch of Int
Medicine, 2002.
Source: Antiretroviral Pregnancy Registry Steering Committee http://www.APRegistry.com Siberry GK et al. AIDS, 2012
Implementation Issues
• Adequate planning for changes in guidelines
• Expansion and integration of ART into PMTCT sites
— Supply chain for ARVs (avoidance of stock-outs)
— Task-shifting for ART initiation
— Adherence, retention, follow up, linkages with chronic ART
— All MCH sites become ART sites
• Access to ART monitoring
Major challenge for PMTCT and MCH settings:
• How to expand access to Viral Load monitoring?
• How to utilize CD4 data, especially for women with high baseline CD4?
Key research questions: Pregnant Women
ARV toxicity surveillance:
• Safety of early, lifelong ART for pregnant and breastfeeding women?
• Maternal toxicity, pregnancy toxicity (stillbirth, low birth weight, prematurity,
birth defects) and infant toxicity?
Mother-to-child transmission and mother and child health impact:
• Impact on overall HIV-free survival and and overall MTCT rate (at the end of
breastfeeding as well as at 6-weeks)?
• Impact on maternal morbidity and mortality, sexual transmission, and the long-
term success of first-line ART?
Adherence and retention:
• Acceptability of ART to women, especially those who initiate lifelong ART
before they meet «adult eligibility» criteria»
• Adherence and retention rates for women with both low and high CD4?
• Health systems and community interventions needed to achieve high levels of
adherence and retention in setting of universal ART?
Rapid Change Towards B/B+
Transition in PMTCT Regimens in the
22 Global Plan Priority Countries
After 2010 WHO PMTCT
As of June 2013
ARV guidelines
Summary
• Major paradigm shift; convergence of PMTCT and ART
• Simplified, harmonized approach for adults and
pregnant women
• All pregnant and breastfeeding women with HIV
should start first-line ART
• With Option B+, all pregnant women with HIV
«eligible» for lifelong ART
1.4 million pregnant women with HIV annually
• Benefit for mother’s health, prevention of infant
infections, prevention of partner infections
Towards an AIDS free
generation
• "The science is clear, and though the road ahead will
not be easy, the opportunity before us is
extraordinary." AMB Eric Goosby, U.S. Global AIDS
Coordinator
2/20/2014 48
