Medicine

1. HIV in Pregnancy
Dr B Vwalika
Consultant OBGyn (UTH)
HOD (UNZA/UTH)
1

2. Background
 Of the 33.3 million people living with
HIV half of these are women in the
reproductive age groups
2

3. Epidemiology
Transmission of HIV
 Unprotected sexual intercourse
 Blood and blood products, donated
semen and organs
 Mother to child transmission (vertical
transmission)
3

4. Epidemiology
Women are at higher risk of
infection than men
 Rate of transmission from male to
female 2-3x higher
 Langerhan’s cells of the cervix
facilitate entry of HIV
 Vulval and vaginal inflammation or
ulceration may facilitate entry of virus
4

5. Epidemiology
 Socio-cultural factors include gender
inequalities, poverty, less access to
education and lack of employment
opportunities
 Traditional practices and customs
such as ‘dry sex’, vaginal douching,
female circumcision and ‘widow
cleansing’ may all have an effect on
increasing risk for women
5

6. Epidemiology
 The desire and societal pressure to
reproduce make it difficult for women
to practice unprotected sex and many
are unable to negotiate for sex safe
6

7. Epidemiology
 The female condom is the only method
independent of the male partner that
women can use to prevent HIV
transmission but it remains expensive and
unavailable in most developing countries
7

8. Effect of pregnancy on the
natural history of HIV
Pregnancy does not accelerate the
progression of HIV
 Although pregnancy is a state of
physiological immune suppression, it
does not accelerate HIV progression
 Percentage of CD4 cells remains
relatively stable
 Viral load remains stable in the
absence of treatment
8

9. Effect of HIV on pregnancy
course and outcome
In advanced disease, there is
increased risk of pregnancy
complications
 Abortions, IUGR, preterm delivery,
LBW, perinatal and infant morbidity
and mortality
 Sexually transmitted infections such
as syphilis, gonorrhoea, candida
9

10. Effect of HIV on pregnancy
course and outcome
 Bacterial infections such as
pneumonia, UTI, TB
 Maternal mortality
10

11. Children with HIV
Background
 Worldwide, more than 2.1 million
children (under 15 yrs) infected with
HIV 2007
 New infections in children 420,000 in
2007
 Deaths due to AIDS in children
290,000 in 2007
11

12. Mother to Child Transmission of
HIV (MTCT)
MTCT of HIV is a result of failed
interventions in women
12

13. Prevalence of MTCT of HIV
Before advent of antiretrovirals:-
 USA & Europe 15-25%
 Africa & S/E Asia 25-40%
The difference was largely due to the
culture of breastfeeding in Africa and
S/E Asia
13

14. Modes of transmission of MTCT
of HIV
 In Utero – Transplacentally (risk 5-
10%)
 Intrapartum- as a result of contact
with contaminated blood or body
fluids (risk 10-20%)
 Postpartum via breastfeeding (risk
10-20%)
14

15. Mother-to-child transmission in
the absence of intervention
0% 20% 40% 60% 80% 100%
60% uninfected
20% 5% 10%
5%
Pregnancy
Delivery
Early BF
Later BF
With ARVs, the absolute risk can be reduced dramatically
to 1%-5%
15

16. Mechanism of transmission of
MTCT of HIV
In utero
The mechanism of transmission from
mother to child is not known. The
maternal and fetal circulation are
separated by trophoblastic
membrane.
Possible theories include:
16

17. Mechanism of transmission of
MTCT of HIV
 Cell-free virus could cross the
trophoblastic membrane by either
infection of the trophoblast of by
passive or active transport to enter
the fetal circulation
 Macrophages in the placenta could
act as reservoirs and transport the
virus to the fetal circulation
 Certain cells in the placenta can
support HIV replication 17

18. Mechanism of transmission of
MTCT of HIV
Intrapartum
 This is largely due to extensive skin
and mucous membrane exposure to
HIV contaminated blood and cervico-
vaginal secretions in the birth canal
18

19. Mechanism of transmission of
MTCT of HIV
Postpartum
 HIV entry may occur through the GIT
following ingestion of virus in-utero or
at birth
 There is decreased acidity, decreased
mucous, lower IgA activity and
thinned mucosa
19

20. Mechanism of transmission of
MTCT of HIV
 Risk may also depend upon factors
such as breast abscesses, mastitis,
nipple cracks, patterns of feeding
(exclusive or mixed), maternal
vitamin A and oral thrush in the child
20

21. Factors Affecting MTCT of HIV
Viral load
 Transmission is increased in the
presence of high levels of maternal
viraemia (>1000 copies per ml, 25%
transmission)
Maternal factors
 Immunological status
 Nutrition
 Behavioural factors
21

22. Factors Affecting MTCT of HIV
 Antiretroviral therapy
 Sexually transmitted infections
 Placental factors
Obstetrical factors
 Prolonged rupture of membranes
 Mode of delivery
 Intrapartum haemorrhage
22

23. Factors Affecting MTCT of HIV
 Obstetrical procedures
Fetal factors
 Prematurity
 Multiple pregnancy
Infant factors
 Breastfeeding
 Immunity
23

24. PMTCT STRATEGIES
24

25. AIDS and
Death
Four Pronged Strategy for PMTCT
Uninfected Parents
to be
HIV infected
woman
Pregnant HIV infected
woman
HIV infected infant
I. Primary prevention of HIV
II. Prevention of unintended
pregnancy
III. Prevention of MTCT
IV. Linkage to Care and
Support
25

26. Minimum package of care for
MTCT
Antenatal Care
 Reduced number of visits and early
access to care
 Supplements and prophylaxis
 Prophylaxis for opportunistic
infections
 Management of STIs
 Male involvement in care
 ART for PMTCT of HIV 26

27. Minimum package of care for
MTCT
Intrapartum care
 Use of a partograph for the
management of labour
 Universal precautions for infection
prevention
 Keeping membranes intact for as long
as possible where labour is
progressing normally
27

28. Minimum package of care for
MTCT
 Vaginal lavage with chlorhexidine
0.25% before each vaginal
examination
 Avoiding invasive procedures as much
as possible
 The provision of ARVs for prevention
of MTCT
 Caesarean section for obstetric
indications
28

29. Minimum package of care for
MTCT
Postpartum care
 Observing the three 6s of postpartum
care
 Supporting the infant feeding choices
made
 Providing continued medical and
supportive care for the patient and
family
29

30. Minimum package of care for MTCT
 Encouraging the use of combined
contraceptive methods
 Referral to community networks
30

31. Feeding options for the
newborn
Breastfeeding is encouraged for HIV
negative women and those of
unknown status. Options include:
 Exclusive breastfeeding up to 6
months
 Breastfeeding up to 12 months
(WHO)
 Formula feeding (replacement
feeding)
Mixed feeding is not an option
31

32. Introduction to ARVs
Three classes of of ARVs in Zambia:
 Nucleoside reverse transcriptase
inhibitors (NRTI): prevent HIV DNA
from entering cell by blocking an HIV
enzyme
32

33. ARVs
 Non-nucleoside reverse transcriptase
inhibitors (NNRTI): prevent HIV DNA
from entering cell by blocking an HIV
enzyme
 Protease inhibitors (PI): prevent the
virus from making new copies of itself
33

34. Adsorption
CD4, gp120
Uncoating
Incorporation
CCR5, CXCR4
Integration
Integrase
Vpr?
Translation
Transcription
Tat, Rev, NF-kB
Assembly
HIV Replication and Inhibitors
RT inhibitor
AZT, ddI
ddC,3TC, d4T
Abacavir
Nevirapine
Protease
Inhibitor
Amprenavir
Saquinavir
Indinavir
Ritonavir
Nelfinavir
34

35. HighlyActive Antiretroviral Therapy (HAART)
Reversetranscriptase Protease
Inhibitor Inhibitor
NRTI NNRTI
GroupA GroupB GroupC GroupD
AZT ddI Nevirapine(NVP) Ritonavir(RTV)
D4T ddC Delavirdine (DLV) Indinavir(IDV)
3TC Efavirenz(EFV) Lopinavir
Fortovase
Abacavir Nelfinavir(NFV)
(ABC)
Nucleotideinhibitor
Tenovofir Amprenavir(APV)
Saquinavir(SQV)
35

36. 36

37. Common Adverse Effects: By Class
 NRTI: Lactic acidosis
 NNRTI: Skin rash, liver toxicity
 PI: Hyperglycemia, elevated lipids, fat
maldistribution
37

38. ARV Protocols for the
prevention of MTCT of HIV
PACTG 076 Regime
 100mg AZT 5 x a day from 14 weeks
gestation until labour. Intrapartum 1-
hour initial dose of 2mg/kg
bodyweight every 6 hours until
delivery. Postpartum 2mg/kg
bodyweight every 6 hours to baby for
6 weeks beginning at 8-12 hours of
birth.
  transmission by 67 % in non-b/fed
infants
38

39. ARV Protocols for the
prevention of MTCT of HIV
Thai Regime
 300mg AZT orally twice daily from 34
weeks gestation. 300mg orally
3hourly during labour. After delivery
no AZT to both mother and baby.
 Transmission 50% non-b/fed
infants and  37% at 3 months,
26% at 24 months in b/fed
infants
39

40. ARV Protocols for the
prevention of MTCT of HIV
HIVNET 012
 Niverapine 200mg orally in labour to
mother and 2mg/kg body weight to
baby within 72hours of birth
  Transmission 41% in b/fed
infants at 18 months of life
40

41. ARV Protocols for the
prevention of MTCT of HIV
Petra A Regime
 AZT 300mg twice daily orally + 3TC
150mg daily orally from 36 weeks
gestation. At onset of labour, 600mg
AZT and 150mg 3TC, then AZT
300mg every 3 hours and 3TC 150mg
orally 12 hourly during labour.
41

42. ARV Protocols for the
prevention of MTCT of HIV
Petra A Regime
 Postpartum, both AZT 300mg and
3TC 150mg twice daily orally, are
given to mother for 7 days.The
neonatal dose for AZT is 4mg/kg
bodyweight every 12 hours and 3TC
2mg/kg bodyweight orally, 12 hourly
for 7 days.
42

43. Zambian protocol- option A
For clients that qualify for PMTCT
provide antiretroviral drugs as
follows:
Antenatal
 AZT 300mg twice daily from 14
weeks gestation or as soon as
possible thereafter
43

44. Zambian protocol
Intrapartum
 AZT 300mg and 3TC 150mg at onset
of labour followed by AZT 300mg +
3TC 150mg every 12 hours until
delivery AND
 NVP 200mg single dose at onset of
labour
44

45. Zambian protocol
Postpartum
Mother
 3TC/AZT (150/300)1 tab each twice a
day for 7 days
45

46. Zambian protocol
Breastfeeding exposed infant:
 NVP at birth and daily until one week
after all exposure to breast milk.
 Start co-trimoxazole from 6 weeks
until a week after all exposure to
breast milk has ended and HIV status
confirmed negative.
46

47. Zambian protocol
Non-breastfeeding exposed infant:
 Commercial milk formula.
 NVP at birth and for 6 weeks.
 Start co-trimoxazole from 6 weeks
until HIV status confirmed negative.
47

48. HAART in pregnancy
 All pregnant women eligible for HAART
should be started on treatment as soon
as possible regardless of gestational
age.
 Those on HAART prior to pregnancy
should continue throughout pregnancy
48

49. HAART in pregnancy
 Counsel the woman and her family about
the risks and benefits of HAART in
pregnancy, for her and her baby
 Consult with an HIV expert if you are
uncertain if the current regimen is safe or if
you are uncertain what the best choices if
change is needed
 HIV infected women should be monitored
according to the same standards for
monitoring non-pregnant HIV positive
women.
49

50. HAART in pregnancy
For women already on triple or
combination therapy:
 Review the ARVs the woman is
already taking
 If taking Efavirenz (EFV) in the first
trimester or a combination of
Stavudine (d4T) and Didanosine
(DDI) These should be stopped and
replaced
50

51. HAART in pregnancy
If the pregnant woman presents for
antenatal care in the first trimester
and is on HAART, there are two
options:
 Continue the drugs without
interruption especially with advanced
disease
51

52. HAART in pregnancy
Temporarily stop all drugs until after 14
weeks of pregnancy if:
 If the patient has severe nausea and
vomiting
 The patient is concerned about the
risk to the fetus of taking ARV in early
pregnancy
52

53. HAART in pregnancy
 If ARVs are stopped for any reason
during pregnancy all drugs should be
stopped at the same time to reduce
the development of resistance.
Remember Efavirenz half life is
72 hours, this period should
effectively be covered with the 2
NRTIs to avoid development of
resistance
53

54. HAART in pregnancy
For HIV-infected women not on ARVS
but may require them:
 Clinically stage the patient according
to WHO staging criteria
54

55. HAART in pregnancy (previous)
Effective combination ARV therapy
(HAART) should be started if:
 Stage 3 or 4 regardless of CD4 count
 Stage 2 if the CD4 count is
<350mm3(<14%) or total
lymphocyte count is <1200
 Asymptomatic Stage 1 if CD4 count
<350mm3
55

56. 56
CD4 criteria for initiation of
ART(current)
CD4 (cell/mm) Actions
<500 Treat irrespective of clinical stage
>500
Treat only if Pregnant, WHO stages 3 or 4, Active TB or
Hepatitis B
NEW

57. Option B plus
 Adopted in 2013
 All pregnant women to start ART for
life regardless of:
 CD4 count
 Gestational age
 WHO criteria
 Breastfeeding-6 weeks of infant
prophylaxis with
once-daily NVP
57

58. Option B plus
 Not Breastfeeding-6 4–6 weeks of
infant prophylaxis with once-daily NVP
(or twice-daily AZT)
58

59. Infant feeding
 Mothers known to be infected with
HIV (and whose infants are HIV
uninfected or of unknown HIV status)
should exclusively breastfeed their
infants for the first 6 months of life,
introducing appropriate
complementary foods thereafter, and
continue breastfeeding for the first 12
months of life.
59

60. HAART regimens in pregnancy
 1. AZT + 3TC + NVP
 2. TDF + (3TC or FTC) + NVP
 3. AZT + 3TC + EFV**
 4. TDF + (3TC or FTC) + EFV**
60

61. CTX PROPHYLAXIS
 Co-trimoxazole is recommended for
all HIV positive pregnant women
after the first trimester.
 The dose of co-trimoxazole for
pregnant women is one double
strength tablet or two single strength
tablets once daily (total daily dose of
800mg sulfamethoxazole and 160mg
trimethoprim).
61

62. 62
Five Goals of ART
3. Reduce
HIV- related
illness &
deaths
4. Improve the
Quality of Life
5. Reduce
risk of HIV
transmission
to others
1. Reduce the
amount of
HIV viruses
in the body
2. Restore &
Preserve
Immune System

63. 63
When to Start ARV Therapy
 HAART is indicated for any patient who meets
the Zambian National Guideline eligibility
criteria.
 All patients must have a confirmed HIV
serology test and should access counseling
services.
 HAART complements the treatment and
prophylaxis of opportunistic infections.
 ALL HIV POSITIVE PREGNANT WOMEN
NEED TO START combination ART (cART)
as early in pregnancy as possible

64. 64
Zambian Protocol for Initiating Therapy
 Before beginning therapy, the decision
should be made with consideration of the
following :
 Is the patient ready and motivated to start
therapy?
 Will the patient be able to have a steady
supply to the drugs?
 Does the patient understand how important
adherence is?
KEY

65. Pregnancy overrides CD4 and
Clinical Criteria for Initiating ART
 All pregnant women should be
initiated on ART regardless of CD4
count or clinical stage
 Greatest benefit of ART experienced
when ART is initiated early in
pregnancy
65

66. 66
Recommendations for Initial Therapy
 First line regimens include two NRTIs + an
NNRTI
 These first line recommendations are for
individuals who have never received ARVs
(including sdNVP) in the past
 It is better to use fixed dose combinations
(FDC) as it means less pills for the patient to
take, which may lead to better adherence

67. 67
Recommended First Line Agents in
Pregnancy
Tenofovir (TDF) +
Emtricitabine (FTC)
OR
Lamivudine (3TC)
+ Efavirenz (EFV)
1st NRTI 2nd NRTI NNRTI

68. 68
Algorithm for choosing NNRTI
Is there a
contraindication
To NVP ?
Is there a
contraindication
To EFV?
•elevated ALT (5 x Normal)
•CD4 >250 in women
Select
Nevirapine (NVP)
• Severe persistent CNS
problems
Select
Efavirenz (EFV)
No
Yes
Yes
No
Must have
CD4 count
result to
initiate NVP
in pregnancy
and CD4
count must
be less than
250

69. 69
ALTERNATIVE FIRST LINE
REGIMEN
Abacavir (ABC) + Lamivudine (3TC) + Efavirenz (EFV)
1st NRTI 2nd NRTI NNRTI
•TDF has been associated with renal toxicity therefore
when calculated CrCl <50 ml/min, it is recommended to
initiate first line therapy with ABC+3TC
•In renal insufficiency requiring dose adjustments of ARVs,
Lamivudine will need to be adjusted

70. 70
Recommended First Line Agents in
Pregnancy in patients exposed to sdNVP
Tenofovir (TDF) +
Emtricitabine (FTC)
OR
Lamivudine (3TC)
+
Lopinavir/r (LPV/r)
OR
Atazanavir/r (ATV/r)
1st NRTI 2nd NRTI PI

71. 71
Algorithm for choosing PI
Is there a
contraindication
To ATV/r
Is there a
contraindication
To LPV/r?
•TB
•Hyperbilirubinaemia/ jaundice
Select
ATV/r
•GI intolerance
•Hyperlipaediamia
Select
LPV-r
No
Yes
Yes
No
LPV/r is preferred PI and
ATV/r should only be used
for LPV/r intolerance

72. End
Any questions?
72