2/23/2016
Pregnancy and HIV
Objectives
Review:
• New material on Pregnancy and HIV
o Canadian data
o Guidelines
o Post-partum & infant feeding
• Present cases and discuss
o Contraception
Mona Loutfy, MD, FRCPC, MPH
o Pregnancy
Infectious Diseases Specialist
o Testing
Maple Leaf Medical Clinic & Women’s College Hospital, Toronto
Prince Albert Parkland Health Region & Ahthakakoop Cree Nation Health Centre, Saskatchewan
Nicole Kimball, RN, BScN
Nurse Clinician
Positive Living Program, Royal University Hospital
Saskatoon Health Region
Mother Infant Pairs by Province
Increasing HIV+ women becoming pregnant
Mother Infant Pairs in Canada
120
Annual Absolute Number
300
Annual absolute number
250
200
150
100
50
0
90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14
Year
100
80
British
Columbia
Alberta
Saskatchewan
60
40
20
0
90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14
Year
*Only 1 case in Yukon (2004) from 1990‐2010 and
thus was not included in the plot above
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2/23/2016
Perinatal transmission & proportion of mothers Missed opportunities 2010‐2014
receiving ART / cART in pregnancy, 1990‐2014
100
Antenatal cART
90
Percentage 80
70
IV ZDV
60
ART
50
HAART
40
Total treated
30
Infected
20
Infant treatment
Uninfected
10
Infected
0
% infected
90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14
Year
Overall in Canada, 0.4% transmission rate
Vertical infections by birth year & antenatal maternal treatment Maternal cART by Province/Territory
1997-2014
16
14
n=116
12
8
6
4
100
80
80
Percent
Percent
10
60
40
No cART retrospective
cART ≤ 4 weeks
40
0
0
0
60
20
20
2
2010-2014
100
No cART prospective
cART > 4 weeks
cART > 4 weeks
cART ≤4 weeks
no cART
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2/23/2016
Maternal cART by risk category
1997-2014
Maternal cART by race
2010-2014
1997-2014
2010-2014
100
100
100
100
80
80
80
80
20
60
40
20
0
0
cART > 4 weeks
cART ≤4 weeks
no cART
Percent
40
Percent
Percent
Percent
60
60
40
60
40
20
20
0
0
cART > 4 weeks
cART ≤4 weeks
no cART
In line with DHHS Guidelines
Predictors of cART duration (2010-2014)
Variable
Race
Risk category
Province
n
≤ 4 weeks
Other
67
4.5%
> 4 weeks p value
Black
587
4.9%
95.1%
White
201
9.5%
90.5%
Indigenous
213
11.3%
88.7%
Other
28
3.6%
96.4%
Sex
773
6.0%
94.0%
IDU
90.6%
95.5%
180
9.4%
Vertical
14
14.3%
85.7%
BC
113
1.8%
98.2%
ON/QC
616
6.7%
93.3%
AB/SK/MN
348
9.8%
90.2%
0.007
0.002
• Centers for Disease Control and Prevention. U.S. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV‐1‐
Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. • March 28, 2014 & August 6th 2015
• http://aidsinfo.nih.gov/guidelines/
0.009
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2/23/2016
Summary of what is new in DHHS Guidelines – March 2014
Summary of what is new in DHHS Guidelines – March 2014
•
•
Expanded Preconception Counseling Section
o Start ART & fully suppress VL prior to conception
o Contraception for those who do wish pregnancy
If an HIV+ woman becomes pregnant on ARVs – do not change ARVs if safe
o More harm from changing; possibility of nausea with new regimen; risk of stopping
Kivexa & Truvada added as Preferred NRTI to Combivir
•
Atazanavir/ritonavir added as Preferred PI
•
Efavirenz now preferred NNRTI after 8 weeks gestation
•
•
Raltegravir – moved to Alternative choice in pregnancy Treating with ARVs earlier in pregnancy – i.e. no later than week 12 of gestation
o Some start ARVs right away when pregnant, even 4 or 6 weeks gestation
•
Summary of what is new in DHHS Guidelines – August 2015
• Added a Section on Pregnant Women diagnosed with HIV in the perinatal period
• Added statement: “HIV infection does not preclude the use of any contraceptive method (AII). However, drug‐
drug interactions with ART and hormonal contraception should be reviewed.”
• More on Reproductive Options
o HIV+ partner in a serodiscordant relationship should be on ART with a suppressed VL
• New HCV drugs do not have enough data in pregnancy; interferon and ribavirin are contraindicated in pregnancy
• Changed to use of IV zidovudine during labour to maternal viral load > 1000/mL; otherwise not needed
• Infant ZDV BID X 4 weeks can now be considered as option (if mother received ART with full suppression and no concern re adherence)
• Also added ZDV + NVP X 6 weeks as choice of ART in infants born to mothers who did not receive ART or only received it intrapartum
• Added section on Post‐partum care including continuing ART (which is to be discussed with their HIV physician
• Also discussed Functional Cure case
Summary of what is new in DHHS Guidelines – August 2015
•
Recommendation of ART use:
•
HIV+ pregnant woman who has never received ART: should start cART as soon as pregnancy or HIV is diagnosed
Drug resistance testing section: has been updated to recommend that regimen be changed based on Resistance testing to maximize suppression as soon as possible
Monitoring HIV in pregnancy: VL test to be done at 34‐36 weeks gestation to inform about mode of delivery
Special populations: linking to AASLD, IDSA, IAS‐USA guidelines. Still lack of safety data with new agents); Updated HIV‐2 testing algorithm Other info: recent data suggests epidural is safe regardless of ARV regimen
Post‐partum: Avoidance of breastfeeding is the strong, standard recommendation but they note that many women may face social, familial and personal pressures
Long term care of infant: risk of mitochondrial toxicity moved here
o NNRTI: Efavirenz remains the Preferred NNRTI if started after 8 weeks gestation; Rilpivarine has been added as an Alternative NNRTI
•
•
•
o HIV‐ partner may be considered*
• General principles of ART: the goal of cART is to maintain an undetectable VL throughout pregnancy for all women
• Recommendation of ART use:
o Preferred NRTIs: still Combivir, Truvada and Kivexa
o Preferred PIs: Prezista/RTV added; Atazanavir/RTV remains
•
•
•
o Alternative PI: Kaletra moved to be an alternative PI
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2/23/2016
DHHS Guideline Review
ARV Therapy
DHHS Guideline Review
Other items
• HIV+ pregnant woman o who has never received cART: should start cART as soon as pregnancy or HIV is diagnosed
o who is on cART, should stay on it and not change what she is on
• Recommendation of ARV Therapy:
o Preferred NRTIs: Truvada and Kivexa, Combivir (not used)
o Preferred PIs: Atazanavir/RTV, Prezista/RTV BID (we use OD) o Preferred NNRTI: Efavirenz after 8 weeks gestation
o Preferred Integrase Inh: Isentress BID
o Alternative: Rilpivarine (as in Complera/used alot), Kaletra
o Rest: not enough data – but many Class B by FDA Pregnancy Class
• Follow up
o Monthly visits with viral load, etc
o TaDP in 3rd trimester
• Elective (booked) C‐section
o At 37‐38 weeks if viral load at 36 weeks > 100 copies/mL
• Post‐partum
o Continue cART
o Formula feeding; counsel on no mixed feeding
o Contraception o Post‐partum depression
o Other issues
Risk Factors for Transmission
Maternal Factors
HIV In Pregnancy –
Viral Load
WOMEN AND INFANTS TRANSMISSION STUDY (WITS): GARCIA ET AL.,  SINGLE MOST RELEVANT: Is she optimally suppressed?






High viral load; especially acute seroconversion
Late HIV disease
Low CD4 count
Maternal injection drug use
Other infections: Hepatitis C, CMV
Presence of STIs
1999 • GC & chlamydia
• Ulcerative ds: HSV & Syphilis
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2/23/2016
Recommendations for Postpartum Care
Transmission with VL < 500 A Case‐Control Study Nested in the French Perinatal Cohort –
27 case of perinatal HIV transmission with VL < 500 copies/mL at time of delivery
Tubiana CID 2010; 50(4): 585‐96.
•Early control of plasma VL was ONLY factor independently correlated with vertical transmission
•Conclusion: “Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV‐1”.
Recommendations for Postpartum Care
Infant Considerations
• Neonatal Prophylaxis to Reduce Perinatal Transmission: ‐ 6 wks Zidovudine for all babes (may consider 4 wks if babe is full‐term & maternal adherence to cART was consistent). ‐ To be initiated as close to the time of birth as possible (preferably within 6‐12hrs of delivery)
• if at higher risk (maternal VL >1000copies/ml or unknown near delivery) addition of 3 doses of Neviripine in the first week of life
Maternal Considerations
• ART Postpartum
• Contraception
o Individualized needs of woman & family as well as clinical factors
o Birth Control Options
•
•
•
•
oral or injectable hormonal contraceptives*
intrauterine devices (IUD)
tubal ligation
condoms
*Many types of antiretrovirals may interact with oral hormonal contraceptives and make them less effective. Therefore, two methods of birth control (including at least one non‐hormonal method) should be used.
Recommendations for Postpartum Care
• If maternal ARV resistance present, consultation with HIV Specialist required to determine alternative prophylaxis
• Virologic tests required to diagnose infants <18mos of age ‐should be done at 14‐21 days, ages 1‐2mos and 4‐6mos
• Pneumocystis jirovecii pneumonia (PCP) prophylaxis –
Septra‐ should be started when ARVs completed (4‐
6wks), unless there is adequate test information to presumptively exclude HIV infection
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2/23/2016
Post partum in Saskatchewan
• Maternal HIV care offered in variety of sites besides the main 3 cities • Majority of babes born to HIV+ mothers are delivered in Regina, Saskatoon & Prince Albert
• PLP team has assisted other facilities prepare for deliveries with mother’s consent/involvement
• Babes born to HIV+ mothers are seen at the 2 tertiary sites for assessment and testing: Saskatoon & Regina
• Only 2 Pediatric Infectious Disease Specialists in SK, located in Saskatoon – see all HIV+ children in SK
Infant feeding
• DHHS Guidelines (Aug 2015) & SOGC (Aug 2014)
‐ Breastfeeding is not recommended regardless of plasma HIV viral load and use of antiretroviral therapy
Saskatchewan Formula Program –free formula for 12mos
In SHR (summary of care):
• Maternal care provided by Positive Living Program &/or by the Westside Clinic team. • Assist with connection to Obs/Gyn, Case Management, etc.
• A maternal health communication form & Standard Orders for mother & infant are completed. Placed on the L&D Unit prior to delivery. • WSCC communicates with the PLP/ID team as well, as ID will be consulted when mom presents to hospital or delivers. PLP does discharge teaching & pediatric follow‐up. PLP Social Worker coordinates the Formula Program prior to delivery.
WHO Principles & Recommendations– 2010
• Revised from 2006, 9 principles & 7 recommendations
were revised/changed
• Principle examples:
• Balancing HIV prevention with protection from other
causes of child mortality (supporting the greatest likelihood of
HIV-free survival, prioritizing prevention against non-HIV morbidity &
mortality)
• Setting national recommendations for infant feeding in
the context of HIV (breastfeeding + ARVs or avoid breastfeeding
within appropriate context)
• Recommendation examples:
• Which breastfeeding practices & for how long
• Conditions needed to safely formula feed (acceptable,
feasible, affordable, sustainable & safe)
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2/23/2016
How can we help support HIV+ mothers?
What does this mean in a Breast is Best world?
•
•
•
•
Social Construct of BF
Social & Cultural expectations
Feelings of Loss & Guilt
Disclosure & Stigma
The HIV Mothering Study by Dr.Saara Greene, Assoc.Professor, School of
Social Work, McMaster University
------------------------------------------------------------------------------------------------------------
• Recent focus group in TO: to further explore the
above, the WHO recommendations & the basic
science of breastmilk and HIV – acknowledging the
positives of BF
-Feedback: all agreed to the above feelings but with increased
knowledge of the science & rates, weighed their feelings of loss
with the risks to their baby and felt that formula feeding was the
best option
• Awareness/empathy of the many fears,
barriers & complex needs of living with/caring
for a chronic illness, as well as, the joy & stress
of pregnancy and motherhood
• Increase knowledge of basic science of
breastmilk vs serum, mechanisms of higher
transmission
• Increase knowledge/support of formula &
preparation, resources, alternative bonding
methods, breast care, assist mother’s to feel
safe & find the positive aspects of formula
feeding
Contraception and HIV
•
Another way that we can help our HIV+ Mothers
Condoms – for double protection – double method = standard
recommendation
– excellent STI/HIV/ contraception but requires cooperation/correct use
- 15% probability of vaginal exposure to semen
•
IUD (Mirena®) - MY FIRST CHOICE
– no known adverse drug interactions with ART; Mirena® less concern for
pelvic inflammatory infection
– Copper IUD also recommended now
•
Depo Provera – MY SECOND CHOICE
– Injection every 3 months
– no known negative drug interactions with antiretroviral therapy
– associated with bone loss; recent link to breast cancer
•
OCP/patch/ring – THIRD BUT GOOD CHOICE WITH NEW ARVs
– Drug interactions with ARVs
– However, can give with some drugs – e.g. Atazanavir, Raltegravir,
Etravirine, Rilpivirine
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2/23/2016
Effect of antiretrovirals on oral contraception
drug
levels
ARV
Effect on EE/NE
Recommendation
NVP
 EE AUC 19%
Do not use
EFV
 NGM AUC 64%
 LNG AUC 83%
Do not use
RTV
(e.g. Kaletra; DRV)
 Levels of OCP
Do not use
ATV
 EE AUC 48%
 NE AUC 110%
OK; OCP < 30 mcg EE
ARV/r > 35 mcg EE
RAL
No interaction
OK
MRV
No interaction
OK
ETRV
 EE AUC 22%
OK
RLP
 EE AUC 14%
OK
ELT/cobi
 PE AUC 200%
OK
DOL
No interaction
OK
High dose EE OCP? No data
Prospective study of 3,790 heterosexual, HIV-1
serodiscordant couples from 7 African countries1
March 28 2014 DHHS Guidelines
Risk Serodiscordant Couples

– Injectable contraception was
more commonly used than
oral pills
– Analysis controlled for age,
pregnancy, condom use and
HIV plasma concentrations
– Significantly increased HIV
risk with injectable
contraceptive use
– Non-significant increase with
oral contraceptive use
Oral PrEP + ART as Prevention in HighPartners Demonstration Project - Africa
o Oral daily TDF/FTC PrEP for HIVuninfected partner in
serodiscordant couple continued 6
mos beyond initiation of ART for
infected partner
o High-risk couples defined as
younger age, fewer children,
uncircumcised HIV-negative male,
cohabitating, unprotected sex in
past mo, high HIV-1 RNA in HIVpositive partner
• Interim analysis
o > 95% of HIV-negative partners
using PrEP
o 80% of HIV-positive partners have
initiated ART; of these, > 90% with
suppression
Hormonal contraception methods and
HIV acquisition?
aHR 1.98
(1.06–3.68)
p = 0.03
aHR 1.97
(1.12–3.45)
p = 0.02
aHR = adjusted hazard ratio
Heffron et al, Lancet 2012
Big NEWS last year !!!!
96% reduction in expected
infections
‒ IRR, expected vs observed: 0.04
(95% CI: 0.01-0.19; P < .0001)
HIV Incidence, Actual vs Expected
Group
Expected
Actual

Infected, n
Incidence/100 PY
(95% CI)
39.7
5.2 (3.7-6.9)
2
0.2 (0‐0.9)
In pts with seroconversion, no TFV
detectable in plasma at time of
seroconversion
o
o
HIV-positive partner in 1 couple not on
ART (high CD4+ count)
Other couple dissolved and HIV-negative
partner in new relationship
Baeten J, et al. CROI 2015. Abstract 24. Reproduced with permission.
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2/23/2016
The START STUDY
• The study details:
o Opened widely in March 2011at 215 sites in 35 countries
o The trial enrolled 4,685 HIV-infected men and women ages
18 and older, with a median age of 36
o Participants had never taken antiretroviral therapy and
were enrolled with CD4+ cell counts in the normal range—
above 500/mm3
o Approx. half of participants were randomized to initiate
ART immediately (early treatment), and the other half were
randomized to defer treatment until their CD4+ < 350/mm3.
o On average, participants in the study were followed for
three years.
Case
• 19 year old First Nation woman homeless in
PA; using opioids and crystal meth –
pregnant and tested in 2nd trimester in Sept
2014 - Negative
• Coming into sexual clinic drop in/needle
exchange daily: For Ensure; retested at 30
weeks
– HIV POSITIVE … infected in Pregnancy
The START STUDY
• The results:
o Based on data from March 2015, the DSMB found 41
instances of AIDS, serious non-AIDS events or death among
those enrolled in the study’s early treatment group
compared to 86 events in the deferred treatment group.
o The DSMB’s interim analysis found risk of developing serious
illness or death was reduced by 53 percent among those in
the early treatment group, compared to those in the
deferred group.
o Rates of serious AIDS-related events and serious non-AIDSrelated events were both lower in the early treatment
group than the deferred treatment group. The risk
reduction was more pronounced for the AIDS-related
events.
Case (cont.)
• Started on Truvada and Tivicay in next few
day; given daily DOT with Ensure
• Viral load = 20,000; CD4+ count = 552/mm3
• Went into premature labour; delivered at 33
weeks gestation; Viral load 67 copies/mL at
delivery
• Baby – HIV POSITIVE at BIRTH –
Conclusion: baby infected in utero
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2/23/2016
What can we do to prevent these cases?
• Prevention
– 3 cases of HIV perinatal transmission in SK in 2015
– Matter of prevention & diagnosis
• Testing
– Test, test, test
– Standard 2nd and 3rd trimester HIV test for all high risk
pregnancies in SK?
– Re-test yearly in methadone clinics
– Expand and continue testing
Questions?
Email: mona.loutfy@wchospital.ca
Cell: 416-725-9566
Email: nicole.kimball@saskatoonhealthregion.ca
Phone: 306-655-6690
• Outreach
– Need nurses, social workers, case managers, community
members out at frontline
11