HIV in Pregnancy

Dr. Andrew Kumwenda

MBChB lecture
23rd June, 2022

Clinical scenario
■

■ You see her and request for routine antenatal investigations. Four weeks
 later, she comes back for her follow up visit to the antenatal clinic and
receive results for her last blood tests you ordered.

■ Her blood results are as follows:

❑ Hb 10.1 g/dL
❑ Blood group O Rh positive

❑ RPR non reactive

❑ HIV 1 - Positive

❑ Hepatitis B surface antigen - positive

❑ Random blood sugar - 4.6 mmol/l

❑ Ultrasound scan shows single live intrauterine fetus at 12 weeks 2 days.

Questions
1. How will you interpret these blood results?

2. What
important issues will you consider when counselling this
woman with the results noted?

3. What specific information do you need from Mrs Shawa’ s history

 and examination?

4. What other investigations, if any, would you like to carry out?

5. How
will you manage this woman antenatally, intrapartum and
postnatally?

6. How will you manage the infant when born?

Basic virology and pathogenesis
■ HIV is an RNA virus belonging to the retrovirus
(Retroviridae) family and subfamily lentivirus

■ Most infections worldwide are caused by HIV-1 infection.

■ HIV-2, a related strain is endemic to West Africa and

 appears less virulent

■ The virus is transmitted by three principal routes: ❑ Sexual

– unprotected anal, vaginal or oral, especially in the presence of
genital ulceration
Basic virology and pathogenesis
❑ Parenteral (blood borne) – sharing of contaminated needles and
unscreened blood products; needles and syringes, sharp
instruments

❑ Perinatal: Vertical transmission (antepartum, intrapartum or

postpartum through breastmilk)

■ Early HIV infection is characterized by a high viral load.

 ■ Main target is the CD4 count lymphocyte population and
lymphocytes are gradually lost during the latent phase.
Basic virology and pathogenesis

■ HIV introduces its own genes into the nucleus of the host
cell

■ It invades and destroys the immune system by damaging

the CD4 lymphocytes

■ Loss of the CD4 lymphocytes reduces both cell mediated

immunity and humoral immunity, leading to the
development of infections and allowing more rapid
replication of HIV
 Incidence and prevalence:
■ Zambia records approximately 48,000 new cases of HIV
annually among adults aged 15-59 years

■ The HIV prevalence seems to have stabilized but at a

relatively high level of 11.3 %

■ 1.2 million people live with HIV in Zambia

■ Prevalence is higher among pregnant women at 16.4 %

Incidence and prevalence:
■ 90%of paediatric HIV infections are acquired through
mother-to-child transmission (MTCT) of HIV.
■ About80,000 of the 500,000 babies born in Zambia
every year are HIV exposed.

■ MTCT occurs during pregnancy, labour, delivery or

breastfeeding
Timing of HIV transmission in pregnancy
15-45% HIV
exposed
children become
infected in absence of intervention

5%
Intrauterine
 10-20%
during
delivery

10-20% via
breastfeeding
Timing of & MTCT risk factors
■ The precise mechanisms responsible for in utero and
intrapartum MTCT still uncertain

■ The placenta appears to be a fairly effective barrier to

infection
■ However, conditions compromising the placental unit (e.g.
chorioamnionitis) and presumably allow the admixture of
maternal and fetal blood have been associated with
increased risk of MTCT
Timing of & MTCT risk factors
■ Situations that ↑ the length of time the infant is exposed
to maternal cervico-vaginal secretions during delivery
also associated with ↑ MTCT risk

❑ This suggests that exposure to maternal blood and

cervico-vaginal fluids, likely through a mucosal portal of
entry (e.g. ophthalmic or gastrointestinal) may account for
MTCT during delivery
■ An ↑ risk has been observed in 1st born twins and
following prolonged rupture of membranes
Timing of & MTCT risk factors
■ In addition, cervico-vaginal ulcers or high maternal
cervical or vaginal HIV proviral copy numbers have been
significantly associated with MTCT independent of
maternal plasma HIV load

■ Breast milk transmission can occur at anytime but

available data seems to suggest that most of it (upto
75%) occurs within the first few months of life

■ The small intestine is also thought to be the more likely

 portal of entry for intrapartum or breastmilk transmission
Timing of & MTCT risk factors
■↓ acidity or relative ↑ in permeability of the GIT may ↑ the
susceptibility of the infants to acquiring HIV

■ High breast milk viral loads and maternal mastitis or

nipple lesions have been associated with ↑ risk of breast
milk transmission
Factors that may affect MTCT-viral factors

a. Highmaternal viral load (most important risk factor) –

MTCT rate is 1% if viral load is <1000 cp / ml

b. Poor immunological status (low CD4 counts and low

 CD4:CD8 ratios)

c. HIV clinical stage - advanced maternal disease

d. Primary infection - Seroconversion (associated with high

viral loads) during pregnancy

e. Resistance to ARV drugs

Factors that may affect MTCT-host
factors
a. Sexual behavior - Unprotected sex with multiple partners

b. Preterm delivery
c. Sexually transmitted infections / other coinfections

d. Duration of membrane rupture - Prolonged rupture of

membranes (>4 hours), doubles the risk of
transmission
Factors that may affect MTCT - host
factors
a. Placental disruption (abruption, chorioamnionitis) b.

Invasive fetal monitoring

c. Use of forceps, episiotomy

 d. Type of delivery – SVD vs C/S
Effect of pregnancy on HIV disease
■ No major adverse effect on HIV progression in
asymptomatic women

■ Those with advanced disease are at high risk of

deterioration in the short term, but this is probably not
accelerated by pregnancy

■ OIs in pregnancy may be less aggressively investigated

or treated because of concerns regarding the fetus,
hence indirectly worsening prognosis for the mother.
 Effect of pregnancy on HIV disease
■ Many of the symptoms may mimic symptoms of
pregnancy (e.g. breathlessness).

■ This is more likely if HIV status is unknown and HIV

positivity unsuspected.

■ Normal pregnancy is associated with depression of cell

mediated immunity and a fall in the CD4 lymphocyte
count, although the % of CD4 cells is unchanged.

■ Similar changes occur in HIV infected pregnant women

Effect of pregnancy on HIV disease
■ No evidence to suggest that pregnancy increases the
risk of progression to AIDS or a fall in CD4 count to
<200/mm3
Effect of HIV on pregnancy
■ HIV (especially if advanced) is associated with
increased risk of:
❑ Miscarriage

❑ Preterm delivery

❑ Fetal growth restriction / low birth weight

■ No suggestion of increased risk of congenital

abnormalities
■ Increased risk of perinatal mortality in developing
countries
Effect of HIV on pregnancy
■ The most dramatic effect on pregnancy outcome is
related to advanced disease and recurrent infections
with poor nutritional status
Striving towards eMTCT
■ Between 2010 and 2020, significant progress was made
in PMTCT

■ However, progress seems to have stalled

■ Exceptional global and national efforts are needed in
several countries targeted for elimination that are home
to nearly 90% of pregnant women living with HIV in
need of services.
Key elements of eMTCT
■ Global plan towards the eMTCT by 2015 recommended
a set of priority actions under four key areas embracing
the WHO four prongs of pMTCT:

1. Preventing new HIV infections among women of

reproductive age.

2. Helping women living with HIV avoid unintended

 pregnancies.
Key elements of eMTCT
3. Access to HTC and that those who test positive have
access to antiretroviral medicines to prevent
transmission during pregnancy, delivery or
breastfeeding.

4. Providing HIV care, treatment and support for women,

children living with HIV and their families.
Pillars / Prongs of eMTCT

Uninfected
Pillars Progression of Parents to be

I. Primary
prevention of HIV
 ARVs, Care and
Support
II. Prevention of
HIV infected
unintended
infant
pregnancy
HIV
infected
Progression
woman
III. Prevention of to AIDS
MTCT
HIV/AIDS
Pregnant
HIV infected
IV. Linkage to woman
 25

Evolution of eMTCT options (WHO)

with a low CD4 Two treatment
count to receive options were
a combination of
Recommended 6

that only women recommende

0
HIV and AIDS
 d • Option A Third recommended
additional
0 2

1
• Option B+
option
1

02 prevent child ion • Option B

drugs to mother to transmiss 02
02

26

Pillars / Prongs of eMTCT

 27

Management of HIV in pregnancy

HIV testing and counselling
■ Universal routine HIV testing is the current policy on HIV
testing in Zambia

■ HCWs are obliged to offer HTS to all who present to

health facilities seeking different services

■ This is provider initiated testing and counselling (PITC)

for ANC

■ PITC means HTC is recommended for women as a

routine component of the package of care
HIV testing and counselling
■ Patients may opt out
 ■ Re-testing - recommended in the 3rd trimester, or during
labour or shortly after delivery, because of the high risk
of acquiring HIV infection during pregnancy.
HIV testing in pregnant and BF women Who
to test When to test What test
Pregnant, unknown status At first ANC visit months if negative
in antenatal care (ANC) Repeat test every 3 Serological
and delivery (L&D)
Test if last test >6 weeks ago
Serological
Pregnant, unknown status in labour
status in postnatal care Repeat test at 6 weeks if
(PNC) negative
Woman of unknown Test at first contact Serological
 months if negative until cessation of
BF
Serological
Breastfeeding Repeat test every 3

Sexual partner At the same times Serological

Lifelong cART
■ All HIV positive pregnant or breastfeeding women should
be initiated on Life-long cART “immediately” regardless of
CD4 count

■ The HIV positive sexual partner is also automatically

eligible for initiating cART irrespective of his CD4 or
WHO Clinical Stage.
 32

When to start cART in pregnant and BF

women
■ The 2010 WHO PMTCT guidelines recommended: ❑
Lifelong cART for women eligible for treatment (based on the
2010 eligibility criteria of CD4 counts ≤350 cells/mm3 or
presence of WHO clinical stage 3 or 4 disease) and

❑ ARV prophylaxis for PMTCT for women with HIV not

eligible for treatment.
■ For those not eligible for treatment, two prophylaxis
regimens were recommended:
When to start cART in pregnant and BF
women
❑ “Option A”, azidothymidine (AZT) for the mother during
pregnancy, single-dose NVP (Nevirapine) (sd-NVP) plus
AZT and 3TC (Lamivudine) for the mother at delivery and
continued for a week postpartum; and

❑ “Option B”, triple ARV drugs for the mother during pregnancy
and throughout breastfeeding.

■ Both prophylaxis options included 4 to 6/52 of peripartum

NVP or AZT for the infant, regardless of whether the
 mother was breastfeeding.
When to start cART in pregnant and BF
women
■ In 2011, Malawi implemented a new approach of lifelong
ART for all pregnant and breastfeeding women with
HIV regardless of CD4 count or clinical stage,
commonly referred to as “Option B+”.

■ WHO issued a programmatic update in April 2012

outlining some of the operational advantages of Option
B and the emerging strategy of Option B+.
When to start cART in pregnant and BF
women
■ In 2013, WHO recommended ART (one simplified triple
regimen) for all pregnant and BF women with HIV
during the period of risk of MTCT and continuing
lifelong ART either for all women or for the women
meeting eligibility criteria for their own health.

■ Option A is no longer recommended

Summary:
OPTION B+
options A and

B+ OPTION A (stopped):

MATERNAL AZT Short Course MOTHER

• Antepartum AZT (from as early as 14 weeks Triple cART from first contact
gestation)
• AZT + 3TC during labor and delivery and sd-NVP Recommended Regimens:
at onset of labor
• Daily AZT + 3TC for 7 days postpartum* (strong • TDF (Tenofovir Disoproxil Fumarate) + 3TC (or
recommendation) FTC) + EFV (Strong Recommendation)

INFANT INFANT

Breastfeeding infant Breastfeeding infant

Daily NVP from birth until 1 week after all exposure Daily NVP from birth for 6 weeks (strong
to breast milk has ended (strong recommendation) recommendation)

Non-breastfeeding infant Non-breastfeeding infant

Daily NVP or sd-NVP + AZT from birth until 4 -6 weeks of Daily NVP from birth for 6 weeks (conditional
age (conditional recommendation) recommendation)

MATERNAL TRIPLE ART

MOTHER

Preferred cART regimens for pregnant

and BF women for Zambia
Descripti 1st line Alternative

on First TDF + XTC (i.e. 3TC or FTC) + TDF + XTC + EFV

DTG (Dolutegravir)
line (Efavirenz) (*TLE)
* Abbreviated as TLD
or

ABC (Abacavir) +3TC+DTG

Second line AZT +3TC +DTG AZT+3TC+LPV-r (Lopinavir

/ Ritonavir)

Mode of delivery (2010 RCOG Guidelines)

■ Decision should be made by 36 weeks of gestation.
■ Delivery by elective caesarean section at 38 weeks to
prevent labour and / or ruptured membranes is
recommended for:

❑ Women taking combination antiretroviral therapy (cART)

who have a plasma viral load > 50 copies / ml
❑ Women taking ZDV monotherapy as an alternative to cART

❑ Women with HIV and hepatitis C virus coinfection.

Mode of delivery
■ Delivery by elective C/S for obstetric indications or
maternal request should be delayed until 39+ weeks in
women whose plasma viral load is <50 copies/ml, to
reduce the risk of transient tachypnoea of the newborn.
 Planned vaginal delivery:
■ Should only be offered to women taking cART who have
a viral load of less than 50 copies/ml.

■ When a woman presents in labour, her plan of care for

delivery should be reviewed and recent viral load
results should be confirmed as less than 50 copies/ml.

■ cART should be prescribed and administered

throughout labour.
Planned vaginal delivery:
■ Invasive procedures such as fetal blood sampling and
fetal scalp electrodes are contraindicated.
■ If labour progress is normal, amniotomy should be
avoided unless delivery is imminent.

■ Amniotomy and possible use of oxytocin may

considered for augmentation of labour.

■ If instrumental delivery is indicated, low-cavity forceps

are preferable to ventouse.
PROM at term:
■ Delivery should be expedited.

■ If the viral load is less than 50 copies/ml and there are

no obstetric contraindications, augmentation may be
 considered.

■ Broad-spectrum intravenous antibiotics should be

administered if there is evidence of genital infection or
chorioamnionitis.
Approach to a HIV exposed infant (HEI)

■ Care for the HEI centers around 4 goals ❑ Preventing

postnatal HIV transmission

❑ Identifying the HIV infected child

❑ Preventing opportunistic infections

 ❑ Maximizing family health and wellbeing
HIV testing in pregnant and BF women
Who to test When to test What test
Well, never
At birth / first week of life or at
NAT
breastfed HIV
first contact
exposed infant
6 weeks NAT
(HEI)
24 months old NAT
Well, breastfed
At birth / first week of life or at
NAT
HEI
first contact
6 weeks, 6 and 9 months NAT
 12 months Serological, if positive, follow up with NAT, if negative, do
serological test at 18
months
18 months Serological, if positive, follow up with NAT, if negative, do
serological test at 24
months

24 months Serological, if positive, follow up with NAT

Preventing postnatal HIV infection (1)

Case scenario Management of the
Infant ARV prophylaxis
mother at delivery and in
and nucleic acid test
PNC
(NAT)

High risk HIV exposed infants

Born to mother with Start or continue cART • All exposed infants to be
established HIV & on cART immediately put on AZT/3TC+NVP
< 12 weeks or mother with for 12 weeks
VL >1000 copies / ml within
4 weeks before delivery

Woman with HIV not on • Start or continue cART • Prophylactic ART

cART or known HIV immediately (AZT/3TC+NVP) until
positive who refuses cART • Continue counselling on confirmed outcome of
need for cART HIV negative after BF
cessation

Preventing postnatal HIV infection (2)

Case scenario Management of the
Infant ARV prophylaxis
mother at delivery and in
and nucleic acid test
PNC
(NAT)
 Low risk HIV exposed infants
Known HIV positive woman Continue cART • All exposed infants to be
on cART >12 weeks put on AZT/3TC+NVP
for 6 weeks

HIV negative women with • Do NAT, if negative, • If NAT on mother is

known positive partner continue PrEP (if she positive do NAT on the
was already on it) and baby
test her every 3 months

Services
■ Screen all women presenting at ANC for Tuberculosis
■ Provide Cotrimoxazole prophylaxis (CTX) to all HIV
positive pregnant women regardless of gestational age,
CD4 count or WHO staging

■ Ensure testing of partners and family members and

linkage to treatment, care and support

48

Services
■ Effective contraception plan:
❑Appropriate family planning counseling and
support

❑Consistent use of condoms during pregnancy,

postnatal and breastfeeding periods

❑ Informed decision making about pregnancy

 choice 49

Infant and young child feeding options

d timing of
Maternal HIV Replacement complete BF
status feeding cessation
Negative or Timing of
unknown complementar At 12 months if
Positive on Recommende y feeding food security
cART d feeding assured
Infant HIV
status Up to 2 yrs if
food security
Exclusive BF not assured
for 6/12 6 months
Recommende
Positive Positive EBF for 6/12 Up to 2 yrs
unknown
Negative or N/A EBF for 6/12 Up to 2 yrs