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Linking HIV Prevention with Early
Care for HIV Infected Infants: Is There
a Need for Innovative Strategies?
Philippe Van de Perre
UMR 1058 INSERM
University Montpellier
CHU Montpellier
EFS
EDCTP Symposium. Every Mother, Every Child… July 20, 2016
HIV care for epidemic control
Ambition versus reality
reality
ambition
37 million people
living with HIV
90% of them know
their status
33 million people
55% of them know
their status
20 million people
90% of them
initiated on ART
30 million people
81% of total
90% of them with
undetectable VL
27 million people
73% of total
75% of them
initiated on ART
15 million people
45% of them with
undetectable VL
7 million people
Anna Grimsrud, CROI 2016
The very best of option B+: focus on Malawi
Andreas Jahn, CROI 2016
100%
90%
80%
81%
81%
73%
78%
60%
49%
48%
3%
PLHIV
HIV status
known
On ART
2%
Retained at
12 months
2%
Virally
suppressed
Jan-June 2015
Jan-June 2011
Access to PMTCT services in 22 priority countries
Pendergast, Arch Dis Child 2015
The Swaziland experience in rolling out B+
 B+ strategy : - Retention in care at 6 months: 68%
- Postnatal retention: 50%
 Modest improvement in retention by B+ versus previous A strategy
 “Further efforts are urgently needed to successfully engage HIV+
pregnant & postpartum women in long term care to achieve the full
benefit of universal care”
E. Abrams, CROI 2016
However, breastfeeding transmission of HIV is an infant’s health
emergency that could not afford waiting for maternal care
improvements
So, what could be done to secure the preventive ambition of B+, while
continuing to optimise the maternal care ambition?
Option B+ and HIV transmission through
breastfeeding?
• Operational constraints to test, treat and retain in
care with the B+ strategy
• High risk of postnatal transmission if
maternal ART is interrupted during
breastfeeding
• Pathogenesis of breastfeeding transmission and
residual transmission: 0.2%/month of breastfeeding
(Rollins, STI 2012)
• Super high risk of selection of resistant viruses in
the baby if defaulted B+ (Zeh, PlosMed 2011; Fogel,
Clin Infect Dis 2011; Lidström, CROI 2010)
Benefit of « super-early » ART in infants
• The « Mississippi baby » (Persaud D, NEJM 2013)
• The CHER trial: persistent clinical benefit of
reducing the size of cellular HIV reservoirs in
children with early ART (H Payne, presented at
CROI 2015)
Prevention and early infant care are indissociable!
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Innovations? (1)
• Reinforce ART adherence (option B+ strategy)
- SMS recall (Mwapasa JAIDS 2014);
- Peer-support (Rosenberg JAIDS 2014) including with
“feeding buddy” (Reimers, JAIDS 2016);
- Improved modes of delivery (Oyeledun, JAIDS 2014);
- Cash incentives for antenatal clinic attendance and
retention in care (Yotebieng, JAIDS 2016)
- Others.
• Point of care test for early infant diagnosis (Chibwesha,
JAIDS 2016)
• PreP for pregnant or breastfeeding women in high
incidence areas (Price, JAIDS 2016)
Breastfeeding and HIV transmission
Innovations? (2)
• Combine maternal ART (B+) with infant PreP or
other infant interventions (passive immune
prophylaxis?)
• Rescue interventions by taking advantage of well
attended contact with health services
Results of ANRS 12174 trial
Lancet 2016
http://dx.doi.org/10.1016/S0140-6736(15)00984-8
Results of ANRS 12174 trial (2)
LPV/r
(N=604)
3TC
(N=607)
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Transmission rate at 50 weeks
1.4% (0.7-2.8)
1.5% (0.8-2.9)
Transmission rate at 26 weeks
0.7% (0.3-1.8)
0.8% (0.3-2.0)
Transmission if antenatal CD4>500
4/335 (1.3%)
2/356 (0.6%)
Transmission if antenatal CD4<500
4/269 (1.5%)
7/251 (2.9%)
1/475 (0.2%)
4/516 (0.8%)
18
15
3.0% (1.9-4.8)
2.5% (1.5-4.1)
95.6% (93.6-97.0)
96.2% (94.3-97.4)
34.6%
32.6%
P
HIV infection (Intention to Treat)
Number of infections
HIV-1 infection (per protocol)
Deaths
Mortality rate
HIV-1 free survival
Children with >1 severe adverse events
0.83
0.19
0.22
0.57
0.82
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PMTCT/B+ in Bobo-Dioulasso, 2d semester 2015
Source: Regional Health Department
•
•
•
•
•
•
•
New ANC attendees:
Tested for HIV:
HIV+ women:
ART initiated during pregnancy:
Infants born to HIV+w:
+/tested by PCR at 2 months:
+/tested at 18 months:
34,462
28,665 (83%)
371
357 (96%)
191
10/168 (5.9%)
8/98 (8.2%)
Conclusions:
1. Huge efforts and success to include HIV-infected women in the option B+ strategy
2. Residual transmission (6% at 2M, probably 14% at cessation of breastfeeding)
Combine maternal ART (B+) with
infant PreP (A)
“Prevention as treatment”
• To assess if the addition of infant PreP with a potent
antiretroviral drug can further reduce HIV-1
transmission at 12 months in breastfed babies
uninfected at birth in whom the mother receives the
current standard of care (option B+)
• To assess the impact of using a potent drug for infant
PreP from birth may serve as a super-early HIV care in
infants infected at birth (better survival, decrease
morbidity, smaller HIV-1 reservoirs)
No risk of overdosage if infant PreP is
given in addition to option B/B+ ?
• Mma Bana study, Botswana
• Low level of ARV drugs in breast milk (ABV, LPV, ABV,
NVP, 3TC, ZDV)
• Median levels BM/plasma: LPV (0.0), ABC (0.85), NVP
(0.27), 3TC (0.75)
• NVP detectable NVP levels were measured in baby’s
plasma, but only occasionally for other drugs
• In untreated breastfed babies: for any drug, no
plasma level > 5% of therapeutic levels
Shapiro RL. Antiviral Ther 2013
Expected outcomes of such
innovative intervention
“Prevention as treatment”
o In HIV-infected neonates and infants: superearly access to potent antiretroviral drug
before diagnosis and ART initiation.
o In HIV-exposed uninfected neonates and
infants: combining maternal ART (option B+
as per national guidelines) and infant PreP
with an expected postnatal transmission rate
near to zero .
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Rescue interventions by taking advantage of
well attended contact with health services
PMTCT-EPI linkage (1)
•
•
In the Bobo-Dioulasso area, almost 100% of infants of 8 weeks of age accompanied
by their mothers attend the first EPI visit
Intervention at EPI visit 1:
 Assessment of previous the PMTCT access
 HIV rapid test to all mothers attending the EPI visit 1
 For those infected, measure HIV viral load and HIV DNA in their babies on DBS;
o If HIV-infected infant: immediate ART.
o If mothers with unsuppressed HIV infection (detectable viral load):
- Infant PreP up to 12 months
- Maternal ART initiation or adherence support
Rescue interventions by taking advantage of
well attended contact with health services
PMTCT-EPI linkage(2)
1.
Monitoring the ‘real life’ efficacy of the PMTCT cascade at the scale of
one city (Bobo-Dioulasso, Burkina Faso)
2.
Allowing access to early antiretroviral therapy for all HIV-infected babies.
3.
Implementing an innovative rescue intervention in order to protect
exposed babies against acquisition of HIV by
• initiating infant PreP until the end of breast milk exposure AND
• initiating ART in HIV-infected mothers who had not been previously
treated (because newly infected since delivery, nonattendance to ANC,
absence of offer to be treated or refusal) OR
• reinforcing ART adherence in defaulting mothers (mothers who initiated
ART during pregnancy or lactation but who dropped thereafter)
Conclusions
• Roll out of option B+ has been extremely successful in terms of
extending access to ART for HIV-infected women
• However, it is not everywhere a panacea in terms of prevention of
HIV transmission to infants. This is mainly the consequence of
operational constraints and breastfeeding transmission of HIV.
• We still need research as there is room for improvements of
existing strategies and innovations
- Reinforcing maternal ART initiation and retention in care;
- Linking prevention and early infant care;
- Reinforcing prevention of breastfeeding transmission
• National and International Agencies are committed to accompany
innovation/research initiatives (EDCTP-2 work plan 2016, NIHPEPFAR PMTCT Implementation Alliance)
Many thanks to...
• INSERM U 1058, Montpellier, France
Nicolas Nagot, Jean-Pierre Moles
• The European-African PROMISE consortium
Thorkild Tylleskär, James Tumwine, Chipepo Kankasa,
Justus Homyer, Nicolas Meda
• Centre Muraz, Bobo-Dioulasso, Burkina Faso
Leticia Sankana, Nicolas Meda
• Regional Health Department, Bobo-Dioulasso, Burkina Faso
Ziemlé Clément Meda
Funds: ANRS, EDCTP, Research Council of Norway
EDCTP/ANRS 12174 investigators at the Arctic
circle, January 2015
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