UPDATE ON
PRECONCEPTION
DR MAHIRAN MUSTAFA
ID CONSULTANT, HRPZ II
CONTENTS
 Background & Epidemiology
 Issues: Health Providers & Clients
 What family planning is about
 What the client should know before
pregnancy
 Conclusion
Reported HIV cases by mode of transmission
and PWID/Sexual transmission ratio, Malaysia
2000-2013
HIV cases by 3 main risk factors (MOH)
Homosexual/Bisexual
100.0
IDU
Heterosexual
Percentage of total cases notified
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
2001
2002
2003
2004
2005
2006
Year
2007
2008
2009
2010
2011
Perbandingan Peratus wanita dijangkiti HIV,
Malaysia vs Kelantan, 1996-2013
30
25
Peratus
20
15
10
5
0
199 199 199 199 200 200 200 200 200 200 200 200 200 200 201 201 201 201
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
Msia 4.2
5
6.4 8.1 9.4 7.9
9
10 10.8 12 15 16.4 19.1 17.9 18.1 20.0 21.0 26.8
Kel
12
11.5 8.6 11.6 16.6 14.6 20.5 15.6
12
10
13
12
15.2 15.9
15
Peratus wanita : 44/207 (21.3%) 2014 : Jan-Jun = 25 kes (20.5%)
21.6 25.6
21
5
SARINGAN PRA-PERKAHWINAN
2007-2013
12
33
42
21
12
6
Jumlah saringan Jan-Jun 2014: 15,996 saringan (20 org)
23
WHY WE NEED FAMILY
PLANNING SERVICES?
4 PRONGED STRATEGIES TO REDUCE
PMTCT
Primary prevention of HIV infection in
women o
Prevention of unintended pregnancy in
HIV+women
Prevention of mother-to-child
transmission (PMTCT) of HIV by:







ART during pregnancy,
Safer delivery practices
Support on infant feeding methods
Provision of care, treatment and support
to HIV-infected parents, infants and
families.
Family Planning Services
It is important today
only 40% of people with HIV know their
HIV status.
 50% of HIV + people is in on-going
relationships have HIV-ve partners ( serodiscordant relationships)
HIV + who know their status, many have
not disclosed their HIV status to their
partners, nor do they know their partners’
HIV status
Family Planning Services
non-pregnant
woman
Pregnant woman
how to stay
HIVnegative
HIV +: access to ART
WHO guidelines recommend offering HIV
testing and counselling to couples, wherever
HIV testing and counselling is available by
Health providers
ISSUES: HEALTH
PROVIDERS
&
CLIENTS
Many Patients Want Clinicians to Ask
About Sexual Issues
 In a survey of adults, 85% expressed an
interest in talking to their providers about
sexual issues
 71% thought their providers would likely
dismiss their concerns[1]
 94% health providers routinely asked
about smoking, 49% asked about STIs,
and 27% about sexual issues
1. Marwick C. JAMA 1999;281:2173-2174. 2. CDC. MMWR Morb Mortal Wkly Rep. 1994;42:988-992.
Survey on Childbearing Desires (UK)
 1998 ->1400 clients
 2011-450 HIV
 28% men
women
 75% wanted
chlidren or more
children
wanted children
 29% women
wanted children
QS 1: Chance or risk of pregnancy
QS 2: Risk of HIV transmission
PRE CONCEPTION: RISK OF PREGNANCY
 No contraception, pregnancy incidence was
15.4% per year
 Oral contraceptive - had comparable
pregnancy incidence to women using no
contraception
 IM contraception had reduced pregnancy
incidence 5.1%
CONTRACEPTION
 CONDOM -Not only prevent
unwanted pregnancy but prevent
sexual transmission of HIV (Grade
A)
 If IUD or hormonal contraception
are to be consider, they must use
together with condom (Grade B)
 NO medical indication for BTL
Final draft CPG HIV in Pregnancy 2008
KKM
PRE CONCEPTION: RISK OF TRANSMISSION
 For HIV negative women, effective
contraception and effective HIV-1
prevention are priorities.
 ART pre-exposure prophylaxis (PrEP) is a
promising new HIV-1-prevention strategy
PARTNER: Risk of HIV Transmission With
Condomless Sex on Suppressive ART
 Observational study of rate of HIV
transmission in heterosexual and
MSM serodiscordant couples (N =
767 couples)
 HIV+ partner on suppressive ART
 Condoms not used
 Analyses: 6-monthly risk behavior
questionnaire, HIV-1 RNA (HIV+
persons), HIV test (HIV-negative
persons)
 Endpoint: phylogenetically linked
transmissions
 Suppressive ART -overall 96%
effectiveness in reducing
transmission
Rodger A, et al. CROI 2014. Abstract 153LB.
Reproduced with permission.
0
Risk Behaviors, %
20 40 60 80 100
HT♀ Vaginal sex with ejaculation
HT♂
Vaginal sex
Receptive anal sex
MSM
Receptive anal sex with
ejaculation
Only insertive anal sex
Rate of Within-Couple Transmission Events
Per 100 CYFU, % (95% CI)
4
0
1
2
3
HT♀
HT
♂
Vaginal sex with ejaculation
(CYFU = 192)
Vaginal sex (CYFU = 272)
Receptive anal sex with
ejaculation (CYFU = 93)
MSM Receptive anal sex without
ejaculation (CYFU = 157)
Insertive anal sex (CYFU = 262)
Estimated rate
95% CI
Sero-discordant Couples
Senario 1: Male partner is infected
 ARV can reduce VL to undetectable levels, but men
can still have a substantial viral concentration in
semen.
 With each act of intercourse , the risk of sexual
transmission must be considered even in the
presence of an undetectable viral load.
 Discussion regarding pre-exposure prophylaxis
(PrEP) for woman partner
 Options include adoption, sperm donation, and
assisted reproduction techniques
Sero-discordant Couples
Senario 1: Male partner is infected
 With each act of intercourse , the risk of sexual
transmission must be considered even in the
presence of an undetectable viral load.
 Discussion regarding pre-exposure prophylaxis
(PrEP) for woman partner
 Options include adoption, sperm donation, and
assisted reproduction techniques
Sero-discordant Couples
Senario 1: Woman partner is infected
 With each act of intercourse , the risk of sexual
transmission must be considered even in the
presence of an undetectable viral load.
 Discussion regarding pre-exposure prophylaxis
(PrEP) for male partner
 Safest option for attempting conception for HIVinfected women with HIV-uninfected male
partners is artificial insemination. However,
working with a fertility specialist can be costprohibitive.
Traia
CAPRISA[1]
(N = 899)
iPrEX[2]
(N = 2499)
Partners
PrEP[3]
(N = 4747)
TDF2[4]
(N = 1219)
Population/Setting
Intervention
Reduction in
HIV Infection Rate, %
High-risk women in
South Africa
 Coitally applied
vaginal TFV gel
39
MSM, transgender
women,
 Daily oral
11 sites in US, South
TDF/FTC
America, Africa,
Thailand
 Daily oral TDF
Serodiscordant couples
 Daily oral
in Africa
TDF/FTC
Heterosexual males
and females in
Botswana
 Daily oral
TDF/FTC
44
 Women: 71; men:
63
 Women: 66; men:
84
62*
 Equal numbers of
infections in active and
FEM-PrEP[5]
High-risk women in
 Daily oral
control arms
(N = 2120)
Africa
TDF/FTC
 Study
lack
1. Abdool Karim Q, et al. Science. 2010;329:1168-1174. 2. Grant RM, et al. N Engl
J Med.stopped
2010;363:for
25872599. 3. Baeten JM, et al. N Engl J Med. 2012;367:399-410. 4. Thigpen MC, et al.
Engl J Med.
ofNefficacy
2012;367:423-434. 5. Van Damme L, et al. N Engl J Med. 2012;367:411-422.
*Underpowered to detect differences between sexes
PrEP Works, but Adherence Is Critical
Study
Efficacy Blood Samples
Overall, %
With TFV
Detected, %
Efficacy By
Blood
Detection of
TFV, %
iPrEx[1]
44
51
92
iPrEx
OLE[2]
49
71
NR
Partners
PrEP[3]
67 (TDF)
75 (TDF/FTC)
81
86 (TDF)
90 (TDF/FTC)
TDF2[4]
62
80
85
Thai IDU[5]
49
67
74
No efficacy
< 30
NR
No efficacy
< 30
NR
FemPrEP[6]
VOICE[7]
iPrEX OLE: 100% Adherence With Daily PrEP
Not Required to Attain Full Benefit
HIV Incidence per
100 Person-Yrs
5
HIV Incidence and Drug Concentrations
< 2 Tablets/Wk 2-3 Tablets/Wk
4-6 Tablets/Wk
7 Tablets/Wk
4
3
Off PrEP
2
1
On PrEP
0
0LLOQ
350
Follow-up,%
26
Risk Reduction,%
44
95% Cl, %
-31 to 77

500
700
1000
1250
1500
TFV-DP in fmol/punch
12
21
12
84
100
100
21 to 99
86 to 100 (combined)
TFV-DP: tenofovir diphosphate (measurable tenofovir in dried blood spots)
Grant R, et al. AIDS 2014. Abstract TUAC0105LB. Graphic used with permission.
QS 3: concern that PrEP potentially
reduces the pregnancy-prevention
effectiveness of hormonal
contraception
RECENT CLINICAL TRIAL OF PREP CONDUCTED
AMONG WOMEN IN AFRICA, MORE PREGNANCIES
WERE OBSERVED AMONG WOMEN RANDOMIZED
TO DAILY FTC/TDF ( PREP) COMPARED TO
PLACEBO
PRE CONCEPTION: RISK OF PREGNANCY
 Study: pregnancy prevention among 1785 HIV-1
uninfected women F/U to 36 months either on
PrEP or Placebo (RCT, placebo-controlled PrEP) .
 Results:
 Did not differ by arm (PrEP 5.1%,
placebo 5.3% per year; P-value for
difference = 0.47).
 Conclusion: PrEP had no adverse impact on
hormonal contraceptive effectiveness for
pregnancy prevention
Pamela M. Murnane et al
AIDS. 2014;28(12):1825-1830
How Do We Decide If a Patient May Be a
Candidate for PrEP?
 Are they at substantial risk of HIV infection?
 Are they able to adhere to a once-daily
tablet regimen?
 What is their likely tolerance of possible
adverse effects?
 Are they able to maintain follow-up
appointments?
 Are there any issues or other concerns?
PrEP & Pregnancy
 PrEP use at conception and during
pregnancy by the uninfected partner offer
an additional tool to reduce the risk of sexual
HIV acquisition[1]
 Potential risks and limited information should
be discussed
 TDF and FTC are classified as FDA
Pregnancy Category B medications[2]-.
 Data on pregnancy outcomes in the
Antiretroviral Pregnancy Registry provide
no evidence of adverse effect among fetuses
exposed to these medications.
1. CDC. PrEP Guideline. 2014. 2. DHHS. HIV Perinatal Guideline. 2014.
Planning For Pregnancy:
Couples HIV +
 Use hormonal contraception and
avoid unprotected intercourse if
pregnancy is not planned
 If plan for pregnancy, options
provided to the couples should
include strategies to minimize HIV
transmission (MTCT)

What Should You Do to HIV +
Mother (Naive)
 Counsel your patients who want to
conceive
 First Things First: Starting a
Suppressive Regimen
 Strategy of selecting an ARTl regimen
appropriate for pregnancy
 Wait until virologic suppression is
achieved
 Ensuring the regimen is well tolerated
 Then proceed with attempting
conception.
Planning For Pregnancy:
Couples HIV +
For the couples:
“early HAART till VL
suppressed”
What HIV + Mother To Be Should
Know: General Advice
 Stressing the importance of taking
their ART regularly to decrease the
possibility of the virological failure.
 Avoid Cigarette smoking,
concurrent use of drugs (cocaine,
heroin)
What HIV + Mother To Be
Should Know
 Mother:
 A possible association exists between
HAART and preeclampsia.
 Glucose intolerance & gestational
diabetes may be more common in
pregnant women with HIV regardless
of the medication regimen. These
women should be screened and
monitored for glucose intolerance.
What HIV + Mother To Be Should
Know
 Baby
 With the implementation of HIV testing,
counseling, ARV medication, safe delivery,
and discouraging breastfeeding, the risk has
decreased from 30% to < 2%
 Rates of prematurity and extreme
prematurity did not differ significantly
according to ARV
 The risk of low and very low birth weight
was greater in the group receiving a PI, but
did not reach statistical significance.
US Antiretroviral Pregnancy Registry. December 2012.
ART and Birth Defects in ANRS
French Perinatal Cohort
Defects With First
Trimester
Exposure, AOR
(95% CI)
Overall birth
defects
Specific organ
system defects
EFV
(n = 372)
ZDV
(n = 3267)
1.3 (0.9-1.9)
P = .31
3.2 (1.1-9.1)
P = .03
1.4 (1.1-1.8)
P = .002
2.5 (1.6-4.2)
P = .001
*French national prospective multicenter cohort studying PMTCT
strategies in HIV-positive women[1]
N = 17,000 (~ 70% of HIV-positive women in France)
13,124 live births exposed to ART in utero
HAART In Pregnancy & ADR
 European collaborative study showed an
increased risk of preterm labor in
women infected with HIV who were taking
combination antiretroviral therapy

OR of 1.8 for HAART without a PI

OR of 2.6 for HAART that include PI
Stillbirth/Abortion Rate According to CD4 &
Prenatal HAART Duration
Baseline CD4+
Cell Count
< 30 D > 3D
> 500 cells/mm3
350-500 cells/mm3
200-350 cells/mm3
< 200 cells/mm3
9.2
8.3
8.8
16.7
3.1
2.8
4.9
7.5
Total
4.1
3.5
5.4
8.6
OR (95%CI)
0.32 (0.15-0.65)
0.32 (0.14-0.75)
0.53 (0.26-1.09)
0.40 (0.20-0.81)
3273 HIV +women with pregnancies
Retrospective analysis of Drug Resource
Enhancement Against AIDS and
Malnutrition (DREAM) cohort 2009
WHO Guidelines on ARV for PMTCT
 New 2010-12 guidelines The PMTCT
guidelines refer to 2 key approaches:
 Lifelong ART for HIV-infected women in
need of treatment for their own health, which
is also safe and effective in reducing mother
to child transmission of HIV (MTCT).
Suggests giving the mother triple ARVs as
soon as they are diagnosed, continuing for
life, regardless of CD4 count
WHO 2012 GUIDELINES
 Short-term ARV prophylaxis to prevent
MTCT during pregnancy, delivery and
breastfeeding for HIV-infected women not
in need of treatment.
MODES OF DELIVERY??
Implement safer delivery Practices
 Elective CS recommended
Patient
not on treatment
Patient on Zidovudin alone or
Patient on HAART regime with viral load
> 1000 copies/ml (GRADE A)
 Vaginal delivery may be opted in
patient on HAART with viral load <
1000 copies/ml (GRADE A)
Should continue HAART thro’out labour
Membrane left intact as far as possible
CPG HIV in Pregnancy Feb 2008 KKM
BREAST FEEDING OR
NOT??
BREAST FEEDING
 Risk of mother-to-child transmission
varies between 15 -20% in non breastfeeding women in Europe and 25 – 40
% in breast - feeding African
population
ARVs to reduce transmission
through breastfeeding
National health authorities should decide on
the strategy that will most likely give
infants the greatest chance of HIV-free
survival :
 breastfeed and receive ARV interventions
OR
avoid all breastfeeding
CONCLUSIONS
 More HIV + persons want conceive or have
children on their own
 With the implementation of HIV testing,
counseling, ARV medication, safe delivery,
and discouraging breastfeeding, the risk of
MTCT has decreased from 30% to < 2%
 Counselling regarding risk of transmission,
pregnancy and early HAART to the couples
are priorities
Let’s do what’s right for
everyone