Transcript slide kit - Women For Positive Action

HIV, conception,
pregnancy and
contraception
Women for Positive Action is an educational program
funded and initiated by AbbVie
Contents
Introduction
Un/planned pregnancy
Vertical transmission (MTCT)
Treatment and care during pregnancy and after childbirth
Routine testing during pregnancy
The need for further research
Case studies
2
Introduction
Women for Positive Action is an educational program
funded and initiated by AbbVie
Women with HIV are an important
but under recognised group
• In 2014 an estimated 36.9 million people were living with
HIV
• 18.5 million of these were women
• Most affected women are of childbearing potential
• In 2013, approximately 1.5 million women with HIV gave
birth
• An estimated 199,000 children were newly infected with
HIV in 2013
4
UNAIDS, Gap Report, 2014
Prevalence of HIV among pregnant
women in Europe and North America
Country
Prevalence (%)
Estonia1
0.48
Ukraine1
0.34
Ireland1
0.31
Belarus, Latvia, Romania, Russian
Federation, Spain, UK1
0.1–0.22
Germany, Italy, Sweden, Poland, Norway1
Canada2,3
<0.1
0.033–0.037
Bulgaria, Czech Republic, Finland, Lithuania,
Serbia and Montenegro, Slovakia, Slovenia1
<0.03
Higher pockets of HIV prevalence among pregnant women have been reported in several
countries e.g. in parts of Ukraine and in and around London in the UK
5
1. Downs et al. IAS 2006;
2. Jayaraman et al. Can Med Assoc J 2003;
3. Remis et al. Can J Infect Dis 2003
Pregnancy – planned and unplanned
•
An important component of care is
preparing for a planned or unplanned
pregnancy
•
With access to optimal management, giving
birth to a healthy, HIV-negative baby is
possible for the vast majority of women of
childbearing age
6
Planning for pregnancy:
Considerations
How do I get pregnant without infecting my partner?
What is the risk that I will infect my partner?
Will pregnancy make my HIV worse?
?
Will the treatment harm me or my baby?
What is the risk of my baby being infected?
Will my healthcare workers treat me differently?
Do I have to have a caesarean?
Should I bottle- or breastfeed my baby?
Will I survive to see my children grow up?
7
Un/planned pregnancy
Women for Positive Action is an educational program
funded and initiated by AbbVie
Unplanned pregnancy
•
Up to 86% of pregnancies in women living with HIV
reported as ‘unplanned’1,2
•
Risk factors for unplanned pregnancy similar to
those for HIV:3
~
~
~
~
substance abuse (the woman or her partner)
mental illness
domestic violence
frequent unstable sexual relationships and unsafe sexual
practices in adolescents
~ crisis conditions and in unstable societies – e.g. war
zones and refugee camps – where extreme poverty and
lawlessness are prevalent
9
1. Loutfy et al. HIV Med 2012;
2. Sutton et al. Obstet Gynecol. 2014;
3. Koenig et al. Am J Obstet Gynecol 2007
Planning for unplanned pregnancies
Anticipate the possibility of
pregnancy in all women
living with HIV who are of
childbearing potential
Consult guidelines and
consider effective cART
regimens that need
minimal modification if
pregnancy occurs
10
Pregnancy intention and desire
•
Research has shown that people living with HIV
face 3 key decisions – disclosure, adherence to
cART and desire for parenthood1
•
Factors influencing the desire and intention to have
children include:2–4
~
~
~
~
~
~
~
~
Younger age
Previous children and number of living children
Access to PMTCT and cART programs
Individual perception of current health status
Spousal, family’s and society’s expectations
Fear of stigmatisation
Ethnicity
HIV disclosure
11
1. Bravo et al. AIDS Rev 2010;
2. Nattabi et al. AIDS Behav 2009;
3. Loutfy et al. PLoS ONE 2009;
4. Mmbaga et al. BMC Public Health 2013
Routine reproductive counselling for
women with HIV is important
In a survey of 700 women living with HIV...
58%
...had not discussed pregnancy or
treatment options before pregnancy
22%
...became pregnant after HIV diagnosis
42%
...had limited/no knowledge of cART
options during early pregnancy
Among women pregnant or considering pregnancy at the time of diagnosis...
48%
...were never asked by a HCP if they
had or were considering having children*
12
Squires et al. AIDS Patient Care & STDs 2011
Routine reproductive counselling for
women with HIV is important
•
Observations from a cross-sectional survey of 181
women living with HIV (15-44 years) and receiving
clinical care at two urban health clinics (USA)
• Personalised discussion: 31%
• General discussion about
pregnancy and HIV: 67%1
• 64% were initiated by the woman1
• There is a greater unmet need for having personalised counselling
about future pregnancies (56%), compared with a need for general
discussions about HIV and pregnancy (23%)1
• Accurate knowledge of MTCT was low (15%)2
13
1. Finocchario-Kessler et al. AIDS Patient Care STDS. 2010;
2. Finocchario-Kessler et al. AIDS Behav 2010
The importance of the patient–HCP
relationship
Help women
to cope with HIVrelated
challenges
Empower women
to be active partners
in their own healthcare
\
Support
Positive relationship
between patient and HCP
Trust
Respect
Compassion
14
Open, two-way,
effective
communication
1. Bravo et al. AIDS Rev 2014
What is reproductive counselling?
Advice, education, and discussion on:
•
Medical issues, including:
• Maternal reproductive health issues
• Effective contraception
• Healthy pre-conception planning to reduce horizontal transmission
• Safe conception
• Reproductive options – risks, costs and success rates
• Vertical transmission and the use of cART or other drugs in
pregnancy
• Impact of HIV on pregnancy
• Impact of pregnancy on HIV
• Other STIs
15
What is reproductive counselling?
Advice, education, and discussion on:
•
Psychosocial and psychological issues, including:
• Long-term health of mother and ability to care for children
• Importance of early and intense antenatal care
• Mental preparation for motherhood
• Psychosocial issues, postpartum impact on adherence and outpatient
visits
• Stigma and fears
• Cultural issues
16
What does reproductive counselling
involve?
•
A two-way interaction to explore coping,
decision-making, emotional reactions and to
plan/prepare for pregnancy
•
Addressing cultural issues and tailoring
counselling to relationship status
•
Advice and education on reproductive
choices
•
The provision of knowledge to help women
make informed choices about having a
family
17
Pre-conception counselling includes
discussion on a risk reduction strategy:
•
Optimise HIV management
•
Choice of cART
•
Screen for and treat sexually
transmitted infections
•
•
•
Encourage sexual partners to
receive HIV testing, counselling
and care
•
Inform partners on fertility
issues, ovulation and the
fertile period within the
menstrual cycle
Advise on the safety benefits of
refraining from unprotected
intercourse, except during the
fertile period of the menstrual
cycle
•
Refer for assessment if
unsuccessful after 3-12
months (earlier if >35 years)
Emphasize the importance of
avoiding unprotected
intercourse once pregnant
•
Avoid genital tract irritants
•
Possibility of treatment failure
and ability to care for child
18
The role of a partner
•
From a woman’s perspective, the support of a partner
may improve health outcomes for mothers and children1
•
Barriers to male involvement in PMTCT, from a male
perspective, can include:2
• Health system factors e.g. antenatal services not male-friendly,
long clinic wait times
• Knowledge gaps e.g. unawareness of services, misconception
that their HIV status will be the same as their partner’s
• Individual factors: e.g. reluctance to take a HIV test
• Societal factors e.g. expectation that antenatal services are a
woman’s domain
19
1. Maman et al. J Midwifery Womens Health 2011;
2. Morfaw F et al. Syst Rev 2013
Conception planning: Prevention of
horizontal transmission
•
Seroconversion in pregnant women due to
transmission from a male partner with HIV remains a
risk1
•
In men with HIV, the desire to have a family is high2,3
~ Despite this, interventions aimed at involving males in family
planning are often limited, with little planning for male
treatment2
•
Scenarios carry different risks and require targeted
strategies to prevent horizontal transmission
~ HIV+ man and HIV- woman (serodiscordant)
~ HIV+ woman with HIV- man (serodiscordant)
~ HIV+ man and HIV+ woman
20
1. Dhairyawan et al. Sex Transm Infect 2012;
2. Sherr & Croome J Int AIDS Soc 2012;
3. Sherr J Int AIDS Soc 2010
Factors and barriers influencing the
acceptability of safe conception strategies1
• Concerns about side effects and treatment
duration with PrEP in those who are HIV-
• Mixed preferences on ART-based and
behavioural strategies
• Generally partnerships where males are
HIV- preferred self-insemination; cART
preferred when women are HIV-
• Manual insemination acceptability
differs between HIV+ and HIV- men
• Knowledge and confidence in
method drives acceptability of
non-ART–based strategies
• Misunderstandings about serodiscordance and
• Limited understanding of female fertility (ovulation) and insemination are important
barriers to consider
21
1. Phofa et al. Presented at 7th SA AIDS Conference,
11 June 2015
Reproductive options
HIV+ man & HIV- woman
•
•
•
•
•
•
Assisted reproduction in case of fertility disorders
Natural conception (if effective viral suppression)
Insemination of donor sperm at ovulation
Treatment as Prevention (TasP) to decrease viral load
Pre-Exposure Prophylaxis (PrEP)
Adoption (where available)
HIV+ woman & HIV- man
• Insemination of partner’s sperm at ovulation (if not on cART / detectable viral
load)
• Treatment as Prevention (TasP)
• Pre-Exposure Prophylaxis (PrEP)
• Natural conception (if effective viral suppression)
• Assisted reproduction in case of fertility disorders
• Adoption (where available)
HIV+ man & woman
•
•
•
•
Insemination of donor sperm or sperm washing to prevent superinfection
Natural conception
Assisted reproduction in case of fertility disorders
22
Virtually no mother-to-child transmission
under effective cART
Reproductive options
HIV-
•
HIV+
HIV+
HIV-
HIV+
HIV+
HIV+ man & HIV- woman
~ Assisted reproduction in case of fertility disorders
~ Natural conception (if effective viral suppression and no
other STIs)
~ Insemination of donor sperm at ovulation
~ TasP with either early or late cART to decrease viral load
~ PrEP with natural conception (if effective viral
suppression and no other STIs)
~ Adoption (where available)
23
1. Loutfy et al, 2013
Reproductive options
HIV-
•
HIV+
HIV+
HIV-
HIV+
HIV+
HIV- man & HIV+ woman
~ Home artificial insemination with partner’s sperm during
ovulation
~ Natural conception (if effective viral suppression and no
other STIs)
~ Assisted reproduction in case of fertility disorders
~ TasP with either early or late cART to decrease viral load
~ PrEP with natural conception (if effective viral
suppression and no other STIs)
~ Adoption (where available)
24
1. Loutfy et al, 2013
Reproductive options
HIV-
•
HIV+
HIV+
HIV-
HIV+
HIV+
HIV+ man & woman
~ Natural conception (if effective viral suppression and no
other STIs)
~ A superinfection risk exists thus cART is crucial
~ IUI, following sperm washing
~ Insemination of donor sperm at ovulation
~ Assisted reproduction, in case of fertility disorders
~ Adoption (where available)
25
1. Loutfy et al, 2013
Pre-Exposure
Prophylaxis (PrEP)
Women for Positive Action is an educational program
funded and initiated by AbbVie
Pre-Exposure Prophylaxis (PrEP)
•
PrEP aims to prevent transmission of HIV through use
of cART before potential exposure to HIV
•
Several clinical trials of topical1,2,5 and oral PrEP2-4,5 in
serodiscordant couples (where the partner with HIV is
not receiving cART) have been completed, with other
trials underway
1. Abdool-Karim et al. Science 2010; 2. VOICE, Available at: http://www.mtnstopshiv.org/news/studies/mtn003;
3. Baeten & Celum IAS 2011; 4. Thigpen et al. IAS 2011; 5. van der Straten et al. CROI 2015 Poster (abstract 979)
Pre-Exposure Prophylaxis (PrEP)
•
In the VOICE PrEP study1 some findings were consistent with
those from previous PrEP trials, however:
•
Different factors were associated with topical vs oral treatment
use, suggesting geographical, demographic, behavioural and
psychosocial differences in people, depending on the route of
administration
•
Several HIV risk predictors were also associated with product
non-use, suggesting that screening of individuals both for high
HIV risk and high likelihood of adherence may be difficult in future
studies
•
The role of partners, alcohol consumption, and economics in
adherence warrants further investigation
1. van der Straten et al. CROI 2015 Poster (abstract 979)
Pre-Exposure Prophylaxis (PrEP)
•
A body of evidence suggests that fully suppressive cART has a
low risk of sexual transmission of HIV1–3
~ Recent studies have shown virtually no mother-to-child
transmission under effective cART
~ Despite this, serodiscordant couples often have concerns about the
risk of transmission4
•
•
•
Natural conception is an option and in some cases PrEP is still
added for individual reasons e.g. fear of transmission or
challenges with adherence
A growing number of studies show the feasibility of PrEP as a
safe and convenient option for serodiscordant couples wishing
to conceive5,6
The decision to take PrEP should be considered in consultation
with a healthcare professional
1. Kancheva Landolt et al. AIDS Care 2015;
29
2. Del Romero et al. Enferm Infecc Microbiol Clin 2014;
3. He et al. PLoS One 2013;
4. Vernazza et al. Antivir Ther 2008;
5. Adeniji et al. J AIDS HIV Res 2013;
6. Whetham et al. AIDS Care 2014
Pre-Exposure Prophylaxis (PrEP)
Trial
Formulation and Dosage
Main aim or results
CARPISA004
1% tenofovir before
and after sex
Incidence reduction by 39%
The first study to demonstrate a positive effect on HIV transmission
VOICE
1% tenofovir
Discontinued due to no efficacy
Emtricitabine/tenofovir
No benefit shown; low adherence potentially due to patient confusion between
prophylaxis and treatment, as well as social stigmatisation fears
FACTS002
Tenofovir
A follow-up from FACTS001, this study aims to test the safety and acceptability of
Tenofovir gel in 16- and 17-year old South African women
Partners PrEP
Study
Tenofovir
62% decrease in transmission risk in both men and women compared with
placebo (p=0.003)
Tenofovir / Emtricitabine
(TVF/FTC)
73% decrease in transmission risk in both men and women compared with
placebo (p<0.0001)
TDF2
Tenofovir / Emtricitabine
(TVF/FTC)
Fewer HIV infections were observed with active PrEP than placebo (9 vs 24),
which resulted in a 62.6% (p=0.0133) efficacy rate
ASPIRE
Dapivirine
2,696 women have been recruited to evaluate a vaginal ring containing dapivirine
for PrEP. Results are expected in 2016
PROMISE
AP ZDV + single-dose
nevirapine (NVP) at delivery
+ tenofovir (TDF) /
emtricitabine (FTC) (tail)*
Higher vertical transmission rates and moderate side effect rates in the two-drug
therapy compared with the three-drug therapies in pregnant women a CD4 cell
count >350 cells/mm3 (n=3523)
DV-lamivudine (3TC) +
lopinavir/ritonavir (LPV-r)†
Associated with a significantly lower rate of delivery <34 weeks and a lower
neonatal death rate than Arm C. Higher HIV-free survival in Arm B compared to
Arm C at 14 days (p=0.002)
TDF/FTC + LPV-r‡
*Arm A; from week 14; nevirapine at delivery (n=1543)
† Arm B; from week 14 and throughout breastfeeding (n=1541)
‡ Arm C; from week 14 and throughout breastfeeding (n=439)
30
HIV and fertility
•
Evidence that HIV/AIDS may decrease female and
male fertility:1
Women
Men
• Sperm parameters affected
include semen volume, motility,
concentration and morphology1
• Men with AIDS are less fertile than
healthier men with HIV-11
• Associated with opportunistic
infections of the genitourinary tract1
• Increased infertility and risk of
sterility, with 25–40% lower fertility
in HIV+ women1
• Associated with STI co-infections1
• Prolonged amenorrhea without
ovarian failure1
• Pregnancy loss is more common1
•
HIV is also associated with:
~ Increased fetal mortality1
~ Decrease in frequency of sexual intercourse
31
1. Kushnir and Lewis, 2011
Assisted reproductive technology for
serodiscordant HIV positive couples
•
•
•
May aid couples in achieving pregnancy while
minimising the risk of HIV transmission
Fertility assistance has important ethical and practical
implications for patients and professionals
Fertility treatment options
~
~
~
~
•
IUI (+/- sperm washing)
IVF
Donor insemination
ICSI
Limited data on IVF/ICSI success
~ Pregnancy rate substantially lower in women living with HIV1
IUI=intra-uterine insemination; IVF=in vitro fertilisation;
ICSI=intracytoplasmic sperm injection
32
1. Barnes et al. 2014
Access to assisted reproduction
options in HIV
Privately / self funded
State-funded
Adoption as an
option?
Guidelines?
Yes
Available in a limited
number of centres
Yes, challenging

Available country-wide
Available in a limited
number of centres
Yes, challenging

Denmark
Available
Yes
Not permitted

UK
Available
Available in some areas
Yes, challenging

Offered by few clinics,
private only
Not available
Yes, challenging

Not available
Available but not in all
clinics
Yes

50% covered by health
insurance
Available in a limited
number of centres
Yes, challenging

Available in a limited
number of centres
Available in a limited
number of centres
Yes

70% covered by IVF Fund
Yes
Yes

Available
No
Yes

Available only in some
provinces
No
Yes, challenging

Country
Portugal
Spain
Romania
France
Germany
Italy
Austria
Switzerland
Canada
Women for Positive Action faculty, 2011
Access to assisted reproduction
options in HIV
•
CREAThE (Centres for Reproductive Assistance Techniques for
HIV in Europe)
~ Provides assistance to couples with HIV
~ Creates a network that guaranteed the careful evaluation and treatment of
these couples
~ The CREAThE network has access to data on a large number of HIV positive
men and women accessing a range of reproductive treatments in over ten
countries
www.creathe.org
Contraception
Women for Positive Action is an educational program
funded and initiated by AbbVie
Access to effective contraception
The ideal contraceptive must be:
•
Safe
•
Reliable
•
Convenient
•
Reversible
•
Prevent transmission of HIV
•
Not interfere with cART
•
Affordable
...currently means that contraception must involve condoms
36
Contraception options in HIV
Method
Advantages
Disadvantages
• STI/HIV protection
• Pregnancy prevention = 85%
• Cooperation needed
• Correct technique
• Inconvenient / may interfere with sexual intercourse
OCPs
• Effective
• Less blood loss
• Pregnancy prevention = 92%
Patch, ring, combo
injectable
• Effective
• Less blood loss
• Pregnancy prevention = 92%
DMPA
• Low maintenance
• Effective
• Pregnancy prevention = 97%
IUD
• Low maintenance
• Effective
• Pregnancy prevention = 99.2%
Cervical barrier
• Reusable/low cost
• Pregnancy prevention = 84%
Sterilisation
• Low maintenance
• Effective
• Pregnancy prevention = 99.5%
• Drug-drug interactions
• Possibly  viral shedding
• No STI/HIV protection
• Possible adverse effects and long-term side effects
• Drug-drug interactions?
• Lack of data
•  shedding?
• No STI/HIV protection
• Possible adverse effects and long-term side effects
• Possible increased risk of HIV acquisition
• No STI/HIV protection
• Possible adverse effects and long-term side effects
• Blood loss with Copper T
• Possible  risk of HIV acquisition
•  pelvic infection
• No STI/HIV protection
•  Urinary tract infections
• Requires correct technique
• No HIV/STI protection
• mostly irreversible, invasive
• Cost
• No STI/HIV protection
Condoms
(male and female)
male; 79% female
1. Sharma and Walmsley. HIV Med 2015; 2. Mostad et al. Lancet 1997; 3. Trussell, Contraceptive Technology 2007;
4. Wang et al. AIDS 2004; 5. Phillips et al. Best Pract Res Clin Obstet Gynaecol 2014
Hormonal contraceptives: long-term
side effects
•
As with all hormonal contraceptives, for example the
contraceptive patch or the pill, a very small risk of some
serious side effects exists:
Blood clots1
Cancer1
• The oestrogen in hormonal contraceptives
can cause blood clots which may lead to:
• Deep vein thrombosis (clot in your leg)
• Pulmonary embolus (clot in your lung)
• Stroke or heart attack
• Presence of other risk factors, which
increase risk of blood clots, may
contraindicate the use of hormonal
contraceptives – e.g. smoking, overweight /
obesity, immobility, migraines, high blood
pressure, family history
•
Slight increased risk of breast cancer;
further research is needed to provide
more definitive evidence
•
Small increase in risk of developing
cervical cancer with the long-term use of
oestrogen- and progestogen-based
hormonal contraception
1. Am H Assoc. Understand Your Risk for Excessive Blood Clotting. 2015. Available at: www.heart.org
38
Hormonal contraception and HIV
acquisition
•
Most evidence does not show a link between
oral contraception and risk of HIV acquisition1
• There has been uncertainty about whether
progesterone-only injectable contraception
increases the risk of HIV acquisition1,2
~ Recent systematic reviews indicate a small
increase in risk with DMPA use
~ WHO (2014) recommend that those considering
this method should be informed of the potential risk
and have access to other HIV preventive measures3
•
Further research is required in this area
39
1. Polis et al. Contraception 2014;
2. Ralph et al. Lancet Infect Dis 2015;
3. WHO, 2014
Interactions between cART and
hormonal contraceptives
Interactions with hormonal contraceptives1
cART class
NRTIs
• No significant risk of interactions with hormonal contraceptive methods
NNRTIs
• Efavirenz - some interaction with COCs and LNG implants
• Etravirine and rilpivirine – no interaction with COCs
• No impact on effectiveness of DMPA
PIs
• Ritonavir – linked to decrease in COC progestin levels
• PIs – no impact on effectiveness of DMPA
Integrase
inhibitors
• Raltegravir – does not interact with COCs
Advantages of specific contractive methods generally outweigh theoretical or proven risks2
cART efficacy does not appear to be impacted by use of hormonal contraceptive methods3
COC=combined oral contraceptive pill
LNG= levonorgestrel
40
1. WHO 2014; 2. Knowledge for Health; 3. USAID
Vertical transmission
(MTCT)
Vertical transmission (MTCT)
•
HIV can be transmitted from mother to child
at various stages of pregnancy and
motherhood:
During gestation1
During labour and delivery2
During postpartum or
breastfeeding1
1. Drake et al. PLOS, 2014;
2. Kind et al, AIDS, 1998.
Minimising the risk of MTCT
Without optimal therapy and prevention the risk of
transmitting HIV from a mother to a baby ranges
from about 12–45%, depending on the setting and
individual circumstances
The risk of vertical transmission drops to less than
1% with optimal intervention
43
Trends in reduction of vertical transmission
in Africa
Impact of the services to prevent mother-to-child transmission
of HIV in 21 African priority countries
35
% mother-to-child transmission
rate (estimated)
•
30
25
20
15
10
5
0
2005
2006
2007
2008
2009
2010
2011
2012
44
WHO 2013
Elimination of vertical transmission –
Cuba & Canada
Cuba1
Canada2
• First country in the world to receive
validation from WHO that it has
eliminated mother-to-child
transmission of HIV and syphilis, June
2015
• In 2014 there was only one case of
mother-to-child HIV transmission in
Canada
• Each year, about 200 babies are
born in Canada to women
diagnosed with HIV
• Achieved through an equitable,
accessible and universal health
system which ensures:
• Near elimination of MTCT achieved
through:
• early access to prenatal care
• high rates of pre-natal testing
• testing for pregnant women and
their partners
• ready access to antiretroviral
drugs
• cART for women who test + and
their babies
• caesarean deliveries and
substitution of breastfeeding
45
UNAIDS 2015; CBC 2015
Factors influencing perinatal vertical
transmission
Factors
Maternal
Obstetric
Infant
Prognostic factors
Detectable
viral loads
Undetectable
viral loads
Lack of awareness of HIV status
3
3
HIV-1 RNA levels
3
3
Low CD4 lymphocyte counts
3
3
Other infections e.g. hepatitis C, CMV,
bacterial vaginosis
3
3
Maternal injection drug use
3
Lack of cART prophylaxis
3
3
HIV infection during early pregnancy
3
3
Non-adherence to cART or incomplete/too late
prophylaxis
3
3
Length of ruptured fetal membranes (ROM)
3
Chorio-amnionitis
3
Vaginal delivery
3
Invasive procedures
3
3
No or inadequate antenatal care
3
3
Prematurity
3
3
Gender
3
3
Low birthweight
3
3
46
3
Reducing vertical transmission:
Issues to address
•
Awareness of HIV infection among women of
childbearing potential
•
Unplanned pregnancy among women with HIV
•
cART should be started in time during pregnancy to
achieve an undetectable VL around delivery
•
Treating co-infections with STI
47
Interventions to reduce vertical
transmission
Exclusive
formula
feeding
Caesarean
section*
Antenatal care
quality and
use
ARTs
Antenatal HIV
testing and
counseling
* In women with detectable
viral load (VL)
Avoid
instrumentation
procedures
during delivery*
Reduced
MTCT
Infection
prevention
practices
48
1. WHO 2013; 2. Teasdale et al 2011;
3. Govender T, Coovadia H 2014.
Breastfeeding
Women for Positive Action is an educational program
funded and initiated by AbbVie
The Mma Bana Study: Low rate of
MTCT with cART
HIV Infections
among live-born
1% overall
infants, n (%)
NRTI group
(ZDV/3TC/ABC)
PI group
Control group
(ZDV/3TC +
(ZDV/3TC +
transmission through
6
months
LPV/r)
NVP)
~ 95% CI for overall
MTCT rate
0.5% to 2.0%
[n = 283]
[n = 270]
[n = 156]
3 (1.1)*§
1 (0.4)
1 (0.6)
0
0
0
Breastfeeding
2 (0.7%)
0
0
Total at 6 months
5 (1.8)*
1 (0.4)
1 (0.6)
In utero
Intrapartum
•
•
•
All regimens of cART from pregnancy through 6 months post partum
resulted in high rates of virologic suppression
No significant difference in the likelihood of MTCT between treatments
The overall rate of MTCT was just 1.1%
*P = NS for difference in between randomised arms; §Result doesn’t include in an infant
who died without a confirmed AIDS-defining cause after a positive PCR result at birth;
Shapiro et al. N Engl J Med 2010
Other PMTCT studies have shown
low transmission rate with HAART
•
MTCT transmission
rate (%)
•
Just 1.1% (8/730) of children across two cART
regimens contracted HIV at 6 months1
In a retrospective analysis of 143 mother-infant
pairs with HIV, transmission rates correlated with
maternal regimen2
25.0
20.0
15.0
10.0
5.0
0.0
No therapy
Single-dose nevirapine
51
Combination
prophylaxis
cART
1. Shapiro et al. AIDS 2013;
2. Buchanan et al. PLoS One 2014
Treatment and care
during pregnancy and
childbirth
Women for Positive Action is an educational program
funded and initiated by AbbVie
Individualising care
Socio-economic
class
Age
Family issues
Sexual issues
Medical history
Pregnancy
Stage of
HIV journey
HIV care should vary
Support
depending on the unique needs
and personal circumstances
of each woman . . .
Immigration
Violence
or sexual abuse
Culture
or religion
Child-bearing
potential
Acceptance
of diagnosis
53
Co-morbidities
(e.g. alcoholism, drug use,
depression)
Language and
understanding
Antenatal care and HIV
Offer essential
health advice
about nutrition
and the
dangers of
substance use
Counsel
pregnant
women about
HIV risk
Offer
continued
advice about
safe sex
Antenatal
care
provides an
opportunity
to...
Provide
information on
peer support
networks
Offer HIV
testing
Advise about
other STIs and
general sexual
and
reproductive
health
WHO, 1998 & 2012; UNICEF, 2012
Individualising care
. . . and consider women in their
social context
e.g. as a mother, a partner,
a daughter, a caregiver
55
Tests during pregnancy
HIV related
Other tests
• Plasma HIV RNA viral
load
• Biochemistry and
complete blood count
(CD4 cell count)
• Antiviral drug resistance
testing
•
•
•
•
•
Tuberculin test
Hepatitis B testing
Hepatitis C testing
HPV screening
Urine and vaginal
cultures
• Pregnancy diabetes
screening
• Other STIs; e.g. syphilis,
gonorrhea, HSV,
chlamydia
56
HIV drug resistance testing in
pregnant women is recommended
•
HIV drug resistance testing in pregnant women
should be performed before starting or modifying
cART regimens when:
~ HIV RNA levels are above the threshold for resistance
testing (that is >500–1,000 copies/mL), prior to initiation of
ARVs
~ HIV RNA levels are detectable and the patient is on ARV
therapy, or when the patient has suboptimal viral
suppression after initiating ARV therapy during pregnancy
•
In order to prevent perinatal transmission, and
ensure maternal health, women who present late in
pregnancy should initiate empiric cART without
waiting for the results of resistance testing and
adjust treatment after test results are available
57
1. DHHS, 2014
Goals of treatment in pregnancy
Optimise
maternal
health
Minimise
maternal
sideeffects
Reduce the risk
of vertical
transmission
Minimise
risk to the
infant
58
What do the treatment guidelines
recommend?
•
Summary of UK (BHIVA), WHO and USA (DHHS)
guidelines for initiating therapy in women who wish
to become pregnant:
•
Boosted protease inhibitors
are preferred
•
Nevirapine
as an alternative
•
Efavirenz
not preferred during preconception or for
first 8 weeks of pregnancy
European (EACS) guidelines for
ART-naïve individuals1
•
cART regimen used in pregnant women
starting cART regimen is the same as in
non-pregnant women, except:
• EFV can be started
•
if other options are not available or suitable
• NVP not to be initiated
•
continuation possible if started before pregnancy
• Among Pl/r, prefer DRV/r or ATV/r
• RAL or DRV/r can be continued
• Avoid ddl + d4t and triple therapy combinations
throughout pregnancy
60
EACS, 2015
General guidelines: HIV treatment in
pregnancy
Pregnancy Scenario
1. Women planning to become
pregnant while on cART
2. Women becoming pregnant
while already on cART
EACS1
DHHS2
Maintain cART, unless on a contra-indicated regimen. If on EFV, switch to
another NNRTI or boosted PI (risk of neural tube defects)
Maintain cART and remain on EFV, provided that the regimen results in
virological suppression. Change regimen only if contra-indicated (ddl +
d4T, triple NRTI).
3. Women becoming pregnant
while treatment naïve
Start cART at the beginning of the
2nd trimester regardless of CD4
levels
Start cART – may delay depending
on CD4-cell count, HIV RNA levels
and maternal conditions (e.g.
nausea, vomiting). Important to
start regimen at ≤12 weeks
4. Women whose follow up
starts after W28 of
pregnancy
Start cART immediately. Consider
adding RAL for rapid HIV-VL decline
in case of high HIV-VL
Start cART immediately.
5. Women whose HIV-VL is not
undetectable ...
… at third trimester:
Start cART immediately. Perform
resistance testing, consider adding
RAL for rapid HIV-VL decline
... in the 2nd half of pregnancy:
Start PI-based cART immediately.
Perform resistance testing if HIVVL >500–1,000 copies/mL and
modify regimen if needed
All cases of antiretroviral drug exposure during pregnancy should be reported to the
61
Antiretroviral Pregnancy Registry (see details at http://www.APRegistry.com)
1. EACS, 2015; 2. DHHS, 2015
US guideline recommendation categories:
Perinatal antiretroviral use in ART-naïve women
Recommended
Alternative
Insufficient data to
recommend useª
Not recommended
• Combination
PIs
NNRTIs
Dual-NRTIs
DRV/r*
ATV/r*
EFV*§
ABC#/3TC•
TDF‡/FTC or
TDF‡/3TC
ZDV•/3TC•
LPV/r*
RPV/TDF/FTC
or RPV*
FPV/r
RPV
IDV/r**
NFV+
RTV
TPV/r
SQV/r
ETR
NVP
Entry
Inhibitors
Integrase
Inhibitors
RAL*
EVG/COBI/
TDF/FTC
MVC
ABC/3TC/ZDV
ddl
d4T†
4
DTG
T20
of zidovudine and lamivudine is recommended as dual-NRTI backbone for women
*Plus a recommended dual-NRTI backbone for pregnant women
# Triple-NRTI regimens including abacavir have been less potent virologically compared with PI-based combination ARV drug regimens.
Triple-NRTI regimens should be used only when an NNRTI- or PI-based combination regimen cannot be used (eg drug interactions)
† Should not be used with didanosine or zidovudine
‡ Preferred NRTI in combination with lamivudine or emtricitabine in women with chronic HBV infection. Monitor renal function
§ Potential teratogenic risk. May be initiated only after the first 8 weeks of pregnancy. Counsel re: teratogenic potential
** Only use when preferred and alternative agents can’t be used. Must give as low-dose RTV boosted regimen
+ Consider in special circumstances for prophylaxis of transmission in whom therapy might not otherwise be indicated when alternative agents are not tolerated
ª Limited safety and pharmacokinetic data in pregnancy; consider in special circumstances when preferred/alternative agents cannot be used
DHHS, 2015
62
BHIVA recommendations on mode
of delivery for women on cART
•
•



For women taking cART, a decision regarding recommended
mode of delivery should be made after review of plasma viral
load results at 36 weeks
Decisions about mode of delivery should take into account :

actual viral load
trajectory of the viral load
length of time on treatment


adherence issues
obstetric factors
the woman’s views
Viral load (VL) at gestational week 36
Recommended delivery mode
<50 HIV RNA copies/mL and absence of
obstetric contraindications
Vaginal delivery
50–399 HIV RNA copies/mL
Consider caesarean section*
≥400 HIV RNA copies/mL
Scheduled caesarean section
*Taking the factors above into account
63
BHIVA, 2014
Post-exposure prophylaxis (PEP) for
infants
Dual therapy1
Monotherapy
For most infants:
• ZDV monotherapy
BID for 6 weeks
(or 4 weeks when the
mother has been taking
cART with consistent viral
suppression)1
• Initiated within 6 to 12
hours of delivery1
In low risk infants*:
For infants born to:
OR
• Untreated mothers
• Mothers with detectable
viral RNA despite
combination therapy
add
• NVP - 3 doses over
the first week of life
• ZDV monotherapy for 2-4
weeks2,3
The decision to combine other drugs with the 6-week zidovudine
regimen should be made in consultation with a pediatric HIV specialist
* Low risk infants = complete antepartum and intrapartum prophylaxis, low viral load at birth, absence of birth complications
1. DHHS, 2014; 2. Neubert et al. BMC Pregnancy Childbirth. 2013; 3. Deutsch-Österreichische Leitlinie zur HIV-Therapie in der
Schwangerschaft und bei HIV-exponierten Neugeborenen 2014)
64
Vertical transmission of HIV when
viral load is suppressed
•
Vertical transmission is possible, although extremely
unlikely, when maternal viral load (VL) is <50 copies/ml
Study
Transmission rate by maternal VL
<50 copies/ml
≥50 copies/ml
UK/Ireland (n=11,515)1
0.09%
1.0%
France (n=5,271)2
0.4%
Not reported
65
1. Townsend et al. AIDS 2014;
2. Warszawski et al. AIDS 2008
HCV coinfection in pregnancy
Prevalence of HCV coinfection in pregnant women in Europe is
~12%1
IDU history, maternal age and area of birth are independent risk
factors for HCV coinfection in pregnancy1
HIV/HCV coinfection increases risk of
vertical transmission of both HCV and HIV2
Around 1 in 10
children born
to women living
with coinfection
have HCV3
IDU, intravenous drug user
More than
twice the rate
of those born
to women with
HCV alone3
Coinfected women
are twice as likely to
have detectable HIV
RNA in the 3rd
trimester/ delivery as
women with HIV
only1
1. Landes, 2008; 2. OHTN, 2010; 3. Benova, 2014
HBV coinfection in pregnancy
There is no evidence of increased mother-to-child HBV
transmission in coinfection over monoinfection1
•
Compared with pregnant women without HIV, coinfected women are2:
~ 3x as likely to test positive for HBV DNA
~ 2x as likely to test positive for HBeAg (a signal of chronic infection)
•
Even with appropriate vaccination, 5–15% of infants born to mothers who test
positive for HBV contract the disease3
~ Up to 39% in women with high HBV DNA levels – often seen in HIV
•
Pregnant women with HBV coinfection have a higher risk of mild hepatoxicity
~ May lead to decreased initiation or discontinuation of ART4
~ cART should include TDF or 3TC in coinfected women to treat HBV as well as HIV
1. BHIVA, 2012; 2. Hoffman, 2007; 3. Kourtis, 2012; 4. Andreotti, 2014
Psychosocial, mental health and
emotional well being
•
Perinatal depressive symptoms are common in
women with, and at risk of acquiring, HIV1
•
Predictors of perinatal depression include:1,2,3
~
~
~
~
Substance abuse during pregnancy
History of psychiatric illness
Childhood sexual abuse
Inadequate social support
• Clinicians should be aware of this risk and
consider routine antenatal and postpartum
screening for depression2
68
1. Rubin et al. J Womens Health 2011;
2. Kapetanovic et al. AIDS Patient Care STDS 2009;
3. Bonacquisti A et al. AIDS Care 2014
Post-partum care
•
Contraceptive counselling should be a critical part of care
•
Decisions to continue cART post-partum should ideally be
taken before delivery and should take into account:
~
~
~
~
~
~
•
current recommendations for initiation of cART
pre-treatment CD4 cell counts and trajectory
HIV RNA levels
adherence
whether the woman has an HIV- partner
patient preference
For women continuing cART post-partum:
~ Arrangements for new or continued supportive services should
be made before hospital discharge because the immediate
postpartum period may pose a challenge to adherence
69
DHHS, 2014
Infant feeding for HIV+ mothers
Is exclusive feeding with infant formula milk affordable,
feasible, acceptable, sustainable and safe?1
Yes
Feed formula
exclusively from
birth2
If on cART and un-detectable viral load, then
closely-monitored breastfeeding may be an
option 2
Prolonged infant
prophylaxis but
not maternal
cART is not
recommended2
Intensive support and monitoring of the mother are
recommended during any breastfeeding period
70
1. WHO, 2012; 2. BHIVA, 2014
Infant feeding for mothers living with HIV
Is exclusive feeding with infant formula milk affordable,
feasible, acceptable, sustainable and safe?1
No
If infant is known to be HIV+, exclusively
breastfeed for six months and continue
breastfeeding up to two years2
If mother is known to be HIV+, and if the infant is
HIV- or of unknown status exclusively breastfeed for
six months and continue breastfeeding up to 12
months, then switch to complementary foods2
71
1. WHO, 2012
Routine testing during
pregnancy
Women for Positive Action is an educational program
funded and initiated by AbbVie
To reduce the likelihood of transmitting
HIV to her infant, a woman must first
know her HIV status
73
HIV testing routinely available in
pregnancy
Austria

Bulgaria

Belarus

Canada*

Czech Republic

Denmark**

Estonia

France

Germany

Moldova, Republic of

Netherlands

Norway

Poland

Portugal

Russian Federation

Slovakia

Slovenia
Spain

Greece
Switzerland

Hungary
Ukraine

Italy
UK

Malta
* Varies by province; **In first trimester

74
1. Mounier-Jack et al, 2008; PHAC, 2010
European HIV-testing strategies in
pregnant women
Opt-in strategy
Opt-out strategy
• France
• Belgium
• Portugal
• Germany/Austria
• Denmark
• Slovakia
• Greece
• Estonia
• Spain
• Moldova
• Finland
• Sweden
• Poland
• Italy
• Switzerland
• Russia
• Ireland
• The Netherlands
• Lithuania
• UK
• Norway
• Ukraine
75
1. Aebi-Popp K et al 2013
Testing recommendations
•
HIV test offered to all women in early pregnancy, or
as soon as possible if late presentation for
antenatal care
• Repeat testing during pregnancy for women with
ongoing HIV risk
• Rapid HIV testing for women presenting for labour
(without a previous HIV test)
• Test results available to appropriate staff on labour
wards
• To offer HIV test to sexual partners of pregnant
women
76
1. BHIVA, 2012;
2. WHO, 2013
The need for further
research
Women for Positive Action is an educational program
funded and initiated by AbbVie
Pregnancy and HIV: More clinical
data and further study needed
•
Data on children exposed to cART in utero
is sparse
~ Difficult to conduct studies in this area
•
Findings based on small studies – clinical
implications unclear
~ Some data show gender differences in MTCT
and in infant resistance
~ But data in pre-adolescents is rarely
disaggregated according to gender
Alternatives needed to address lack of data and
to clarify clinical significance of findings
78
Antiretroviral Pregnancy Register
•
•
•
•
•
Only project to evaluate first trimester (and
later) prenatal exposures to cART
Gathers anonymous data on foetal/maternal
outcomes
Provides important information to complement
clinical trial data
Data will assist clinicians/patients in weighing
potential risks and benefits of treatment
Pregnant women on cART should be
encouraged to participate in registry
www.apregistry.com
79
Rate of birth defects in live born infants
•
Overall rate of birth defects for infants exposed
to cART in utero is:
~ Similar for 1st trimester and 2nd/3rd trimester exposure
~ Not significantly different to the rate in other birth
defect registries
Overall (%)
95% CI
1st trimester
212/7383 (2.9%)
2.5% - 3.3%
2nd/3rd trimester
246/8765 (2.8%)
2.5% - 3.2%
Any trimester
460/16150 (2.8%)
2.6% - 3.1%
1st to 2nd/3rd trimester prevalence ratio
1.02
0.85, 1.23
80
Antiretroviral Pregnancy Registry Steering Committee, 2014
Future research and specific clinical
questions and needs
Breastfeeding
when viral load
is undetectable
Optimising neonatal
regimens for perinatal
assessment of drug
resistance
drug safety and
pharmacokinetics
Stopping
cART
Hormonal
contraception and
HIV progression
Optimising
adherence
Offering latepresenting women
rapid testing at
delivery
?
?
?
?
?
?
81
Role of caesarean
delivery among women
with undetectable viral
load or with short
duration of ruptured
membranes
Case studies
Women for Positive Action is an educational program
funded and initiated by AbbVie
Case study: Former IV drug user
•
25-year-old female, HIV+
• 8 weeks pregnant
• Former IV drug user
~ Relatively stable on methadone
maintenance
•
Hep C positive (antibody and PCR)
As well as managing her treatment and
delivery with respect to her HIV/co-infections
what other issues should be considered?
83
Issues to consider
Mental health and emotional well being
• Women are more likely to be diagnosed with
mental health and emotional problems than men
• Pregnancy and substance use problems increase
the risk of emotional or family problems women
with HIV
• HIV diagnoses made during pregnancy are
associated with a higher incidence of mental health
issues, (e.g. postpartum depression) than nonpregnancy diagnoses
• Not all HIV clinics have good access to perinatal
psychiatric services
• Peer support and mentoring can help
84
Issues to consider
Disclosure
• Disclosure to partners is encouraged
• HIV testing of other children is recommended
• Pregnancy is key window for disclosure
• A woman is more likely to disclose during
pregnancy, but if she doesn’t disclose then she is
likely to do so postpartum
• Disclosure may occasionally have unwanted
consequences
Adherence
• Enrol in adherence support programme/workshop
• Adherence and follow-up
85
Issues to consider
Post-pregnancy contraception
• Still no ideal contraceptive available
• If partner is HIV negative – condoms recommended
• In cases of full viral suppression, stable partnerships
and no other STIs, there is minimal risk of
transmission. How should questions about
this be handled?
• Many ARVs interact with hormonal contraceptives
86
Case study: Discordant HIV test
result
•
33-year-old woman and male partner undertake
HIV screening before stopping condoms and
planning a family
•
Woman screens HIV+ while
partner screens HIV-
•
Woman refuses to inform partner of her HIV+ result
for fear of abandonment
As well as managing her diagnosis and potential
pregnancy, what other issues should be
considered?
87
Issues to consider
Disclosure and doctor-patient confidentiality
• Many national guidelines preserve confidentiality to
patients except in special circumstances
• Pre- and post-test counselling should openly
discuss HIV+ outcome and propose how to prepare
for ‘bad news’
• Cases of prosecution for the transmission of HIV,
as well as doctors being criminally liable for nondisclosure
• Disclosure without the woman’s consent may be
mandatory in some countries but will also have
consequences for trust within the doctor-patient
relationship
88
Prosecution for the transmission of HIV
•
In many jurisdictions the law is unclear in this area, varying
widely from country to country
•
It is unlikely that a person could be successfully and ethically
prosecuted for unintentional HIV transmission
•
Some convictions in Europe have occurred in rare cases
where individuals were aware of their status
89
Case study: Refusal to refrain from
breast feeding
•
African migrant living in Europe
• Stable on cART
• Living in shared state-provided
accommodation
• Gave birth to HIV- boy, but planned to
breastfeed while refusing to
administer cART
• Believed that “God would look after
him”
As well as managing her treatment, what
alternatives should be considered?
90
Issues to consider
Social support, duty of care to mother and baby
• Address patient’s housing situation so that she no
longer shares a room. This may change her
opinion about treating her baby
• Seek community support, e.g. community faith
leaders
• Encourage use of peer support networks
• Faith leaders can also help to encourage
adherence and issues related to stigma
• Some guidelines suggest that breastfeeding
accompanied by medical counselling and support
is possible, even if not recommended1
• Possible legal consequences of breastfeeding?
91
1. BHIVA, 2014
Religion, beliefs and spirituality
•
Beliefs are important
for many women with
HIV
•
Wherever possible it is
more effective to work
‘with’ beliefs, not
‘against’ them
•
Use of faith leaders
and ‘stories’ can
improve engagement
92
Thank you for your
attention
Any questions?
Women for Positive Action is an educational program
funded and initiated by AbbVie