HIV IN PREGNANCY

BY

DR. J.U.E. ONAKEWHOR, MBBS, M.SC, FWACS, FICS

(Consultant Ob-Gyn and Coordinator, PMTCT Program, UBTH, Benin
City)
Presentation made at the Revision Course organised by
the National Post Graduate Meidcal College of Nigeria
ath the University of Benin Teaching Hospital ,Benin
City, Nigeria September 5- 10 ,2005.
INTRODUCTION

 Since man fell from the throne of

grace
 Health Problems have become
insurmountable
 The Lord will strike you with the
dxes of the Egyptians; boils,
tumours, scab, itch, madness,
blindness, confusion of heart from
which you cannot be healed.
- Deut, 28:27-28.
 OVERVIEW OF THE HIV BURDEN
 5 cases of P CP 1st reported from the University of
California, Los Angeles, United States and published on
June 5, 1981MMWR (24 years ago)

 Was initially called Gay men ( homosexual men) ’s

disease

 HIV / AIDS has become a global pandemic

 Nigeria officially reported her first case of HIV/AIDS

in a 13-year-old girl in 1986

 Curtailing this infection - the concern of everyone

 Overview cont.
In Africa:
 Malaria infection –500 M /YR, HIV– 22M /YR:⇒
most common Dxes in Africa
 HIV /AIDS epidemic + its ramification getting out of
control
 Spread of HIV/AIDS in Africa > worse than projection;
 2.4M died of AIDS in sub-Saharan Africa in 2000
( 80% of global AIDS deaths).
 AIDS leading cause of death in Africa; 4th worldwide
 GLOBAL PERSPECTIVE OF
HIV/AIDS
• HIV/AIDS is global problem- no continents is spared

 An estimated 37.8 million [34.6–42.3 million] people infected

worldwide:

 Infected adults 35.7 million [32.7–39.8 million];

 Women most affected -17 million [15.8–18.8 million] infections world

wide.

 Sub-Saharan Africa is home to 25 million people(70% of the world

infected population). (UNAIDS 2004).

 Africa contributes only 11% to the world population of over 6billion.

 GLOBAL PERSPECTIVE OF HIV/AIDS contd.

 New infections in 2003 - 4.8 million [4.2–6.3 million]

people

 AIDS deaths in 2003 : Globally, there were 2.9 million.

 Adult deaths were put at 2.4 million.

 Deaths of children under 15yrs was about 490,000

(UNAIDS 2004)
GLOBAL PERSPECTIVE OF HIV/AIDS contd.
 15,000 new infections occur every day.
 9-10 infections per minute
 ONE infection in 6 seconds
 About 1 death every 10 seconds
 > 95% of the infections occur in poor & developing countries

• Africa remains the world’s burden.

• The life expectancy in some African countries has dropped from 62 to

47 years.

• Economically, the hardest hit countries could lose more than 20% of
their Gross Domestic Product (GDP) by the year 2020 due to AIDS
from ill-health and death of the work force.
HIV IN NIGERIA
National prevalence;
• 5.4% in 1999
(1.8% in 1991,3.8% in 1993,4.5% in 1996)
• 5.8% in 2001 (`17. 0% in TB patients)

In Benin City
• 0.00% in1992 • 1.8% in1993/94
• 2.4% in 1997/98 • 5.8% in 2000
• 8.5% in Dec.2001 • 9.4% in June 2002
 HIV in PREG _ in 2000 SPCH, B /C
PREVALENCE FOR THE MILLENNIUM YEAR, 2000

QUARTER PREVALENCE (N=1,024 )

1st 2nd 3rd 4th

9/59 13/59 16/59 21/59
(15.3 %) (22.0 %) (27.1 %) (35.6 %)

Note increasing trend

 BAR CHART SHOWING QUARTERLY
SEROPREVALENCE OF OBSTETRIC HIV AT
THE SPCH, B/C in 2000.
25

20

15

10

0
1st Qtr 2nd 3rd Qtr 4th Qtr
Qtr
PATHOPHYSIOLOGY :HIV Lifecycle
 HIV is a retrovirus that uses its RNA and the
host’s DNA to make viral DNA. It has a long
incubation period.
 HIV consists of a cylindrical center surrounded
by a sphere-shaped lipid envelope. The center
consists of two single strands of RNA.
 HIV causes severe damage to and eventually
destroys the immune system by utilizing the
DNA of CD4+ lymphocytes to replicate itself,
destroying the CD4+ lymphocyte.
 PATHOPHYSIOLOGY contd

Serotypes: HIV-1 and HIV-2.

 HIV-1 more deadly and commoner and is more widely
studied than HIV-2.
 HIV-1and 2 are both present in West Africa;

 HIV-1 is the commoner of the two.

 HIV-2 commoner in West Africa than in any part of the

world,
HIV-2 is milder in its course than HIV-1; it does not seem
to respond appropriately to the conventional drugs
used in the treatment of HIV-1. Also, its laboratory
(confirmatory) diagnosis is more strenuous.
 Subtypes of HIV –1.
 HIV-1 is the major cause of AIDS.
 Like other retroviruses, it can make in the host cell nucleus a DNA
copy of its RNA genome- a reversal of the normal direction of
genetic flow.
 mean plasma half-life of only 6 hours, a feature that is responsible
for the very frequent mutation of the organism.
 There are three genes in the RNA genome.
- ‘env’ gene encodes for envelope proteins including gp120.
- gp120 is responsible for ‘locking into the CD4 lymphocyte cell
receptor.
- The ability of the virus to evade immune surveillance is based on
the variability of this protein.
- CD4 Lymphocyte plays invaluable role in immune response of the
host and is the main target of attack by the virus.
- Depletion of the host CD4 cells is a measure of the degree of
spread of the infection within the host
Human Immunodeficiency
Virus
HIV Structure
 CD4+ T cell or macrophage

THE HIV LIFE CYCLE

 Subtypes of the HIV-1 organism
 Subtypes A, B, C, D, E, F, G.
 The G subtype in Nigeria was first identified in Ibadan.
 The Clade AG virus present in Nigeria.

Implications of this genetic diversity may include

-possible differences in natural history between subtypes,
-shorter time to AIDS (in some cohorts),
-difference in viral load pattern,
-mutation resistance patterns to anti-viral drugs

-the need for and difficulties in developing ‘cocktail’ vaccines that are
effective against these various strains.

-The natural history of the Clade AG virus, the viral load and mutation
resistance patterns in Nigeria may be different – evaluated needed.
 Incubation period
 One to three months to develop detectable antibodies after initial
exposure.
 median time may be less than four weeks,
 seroconversion may take longer to occur.
 During this asymptomatic phase of viraemia, billions of virions are
produced,
 infection transmission may be high and progressive attrition of the
immune system takes place.
 CD4 lymphocytes depletion rate of about 60 x 109 /L / year
 Clinical AIDS in about ten years for some individuals ;
 it may be shorter in some individuals

- depending on the virulence of the offending organisms,

- the genotype and phenotype of the virus
- the viral load (plasma HIV RNA)
- viral resistance.
- Other factors : maternal, obstetric, fetal and infant factors
( MTCT)
 In Africa Contd.

 Factors responsible for the HIV spread in

sub-Saharan Africa:
 Poverty; lack of resources
 Denial
 Stigma
 Complacency
 Life expectancy ↓ ; 67-→ 47 yrs
(Nigeria – 52 yrs)
 Media For Transmission Of HIV

 HIV can be transmitted through exchange of

body fluid such as
 Blood and blood products

 Semen

 Vagina fluid

 Breast milk

 Saliva

 Donated organs for transplant

 Mode of transmission of HIV

• Mother-to –Child transmission

 Heterosexual intercourse (Semen, Vagina fluid)

 Blood transfusion (blood and blood products)

 Incidental needle punctures especially for medical staff,

 Sharing of needles by intravenous drug abusers,

 Sharing of other sharp unsterilized instruments for

medical, social or cultural purposes (e.g. tattoos).
 Sharing of Clippers, toothbrushes, etc.
 Diagnosis of HIV/AIDS
The diagnosis of HIV is based on
3. Detection of HIV- antibodies in the serum of an individual using

i). Double ELISA (Enzyme-linked immuno-absorbent assay) test

ii). Rapid test (Double/ Triple test) Algorithm (WHO)
iii). Western Blot,
iv). Immuno-precipitate assay
v). Immuno-florescent assay

2. Detection of HIV - specific antigen for example the p24 antigen

3. Detection of HIV nucleic acid- using the Polymerase Chain Reaction

(PCR) technique( RNA-PCR and DNA-PCR)

4. Viral culture.

5. Apart from laboratory, clinical diagnosis is also important when the

patient is symptomatic. BUT Lab, confirmation mandatory
Most diagnosis and classifications use a combination of the CD4 lymphocyte count and symptoms.
Others

• Dry blood spot testing for viral antibodies (In rural hospitals or in
resource–poor settings) is an acceptable method

• Dual rapid tests for “same-day” rapid test results same day
diagnosis in antenatal clinics provided the two kits have different
working principles.

advantage:
-early results
- enabling the antenatal women more access to antenatal strategies
for the prevention of vertical transmission

Voluntary counseling and confidential testing (VCCT) is universally

recommended.

Testing & Counseling( TC) now recommended for health facilities

Routine screening with op-out option (practiced in some maternity
centres worldwide).
 T he CDC Classification of HIV disease

The CDC 1993 revised classification of HIV

disease ( still widely in use)
Three Categories; corresponds to three CD4
Lymphocyte categories
A: CD4 >500 cells/mm3 (CD4% >28%),
B: CD4 200-499 cells/mm3 (CD4% 14%-28%),
C : CD4 <200 cells/mm3 (CD4% <14%).

-These are symptom categories ;

-recommended to “guide clinical and therapeutic management actions
-in HIV-infected adolescent and adults”.
 Clinical and Immunologic Staging
Laboratory Clinical Axis
axis
CD4 Stage 1 Stage 2 Stage 3 Stage 4
Asymptomatic Early HIV Intermediate Late
PGL AIDS

A >500 1A 2A 3A 4A

B 200-500 1B 2B 3B 4B

C <200 1C 2C 3C 4C

• Hashed area represents those with case definition of AIDS

(stages 1C, 2C, 3C, 4A, 4B, 4C)
 Vulnerable group
• Young persons most predominant vulnerable
group (15-49; the younger the age the more likely
the risk of infection).

 Women

 children
 WHO ARE AT RISK OF HIV ?
 All unmarried sexually active persons
 Married but unfaithful couples ( ↑ sero- Discordances)
 Blood transfusions
 MTCT; over 90% of vertical transmission
 Homosexuals
 I.V Drug abusers
 Health hazards (medical / health workers)
 Persons with STIs
 Low social economic class, esp.20-39 yrs(78%)
 Sharing sharp unsterilized objects (harmful traditional
practices- scarifications , tattooing, ear piercing,
circumcision, manicure, pedicure, clippers, etc.)
 INTERVENTIONS
 HIV -developed countries ; now a treatable chronic dx
 Developing countries; a major health problems
-2nd most killer after malaria
 Microbicidal agents - 60 candidates

 AVRS / HAART-currently the mainstay of MX

 Vaccines –over 30 types under clinical trials vs HIV- 1
Sub-type B&E in phase 3 clinical trial

Predominant sub-types in S.S.Africa are A, C, D

 Recombinant viruses-AG in Nigeria.
 Prevent new infections- PMTCT in pregnancy
 Cocktail Vaccine – the most appropriate
 Intergenerational sex and HIV
infection of young women
 Transmission of HIV from older to younger
people is necessary to maintain virus in
population- without sex between older and
younger populations epidemic would fade as
infected persons age
 Pressures on young women to have sex or marry
older men
 Dominance of older males in society
 Family pressure
 Economic
 Social status
 PMTCT Using Antiretroviral
(ARV)
Treatment versus Prophylaxis
 ARV Treatment
Long-term use of antiretroviral drugs
to treat maternal HIV/AIDS and prevent
PMTCT
 ARV Prophylaxis
Short-term use of antiretroviral drugs
to reduce HIV transmission from
mother to infant
Challenges in PMTCT
 Preventing HIV in young women
 Preventing unintended pregnancy in HIV+
women
 Diagnosing HIV early in pregnant women
 Getting ARV prophylaxis started before
transmission can take place
 Reducing transmission risk at term
 Preventing transmission from breast milk
while protecting child against diarrhea and
malnutrition
 Avoiding ARV resistance
 PMTCT: Four targets for a
comprehensive approach
 Prevent young women from becoming
infected
 Prevent unintended pregnancy in HIV-
infected women
 Prevent HIV-infected women from
transmitting HIV to their infant
 Provide HIV care, treatment, and support
to HIV+ women, their infants, and their
families
Risk of mother-to-child transmission of HIV
without intervention*
Exposure Transmission Cumulative risk
risk (%) (%)
1st trimester <1 <1
2nd trimester 2 2
3rd trimester 5 7
Labor & delivery 12-14 19-21

24 months 12-18 31-39

breastfeeding

*Consensus estimates from multiple studies

Risk of mother-to-child transmission of HIV during
pregnancy, delivery, and breastfeeding
1st trimester
2nd trimester
3rd trimester
Labor &
delivery

24 months
breastfeeding
Uninfected
 Goals of Antiretroviral Therapy in Pregnancy PMTCT

• Improve maternal health status

.prevent mother to child transmission of HIV
Achievable through :
- Maximal long-term viral suppression
- Optimal immune reconstitution,
- Reducing the risk of resistance and cross-resistance to the
antiretroviral agents,

- Minimizing drug toxicity to the mother

- avoiding drugs with fetal teratogenic effects.

- Enhancing the quality of life and the overall clinical outcome for both
mother and baby at affordable cost of care.

- Finally the objective of this care is to integrate with long-term public

health efforts.
modalities

 ANC
 LABOR, Vag. Deliv &C/S

 POST NATAL
Enrolling and retaining women and
children in PMTCT

 Follow up of infants
 Must monitor infants to measure
program outcome
 Nutritional support
 Testing for HIV
 TMP/SMX (Bactrim) prophylaxis
 An avenue to getting mothers, fathers,
& siblings tested or into care
Monitoring ARV therapy
Laboratory data
 Absolute minimum tests per WHO
• HIV test
• hemoglobin or hematocrit level

 Basic tests
• WBC or FBC
• Total lymphocyte count
• Liver function tests (LFTs)
• Renal function tests (RFTs)
• Blood sugar

 Desirable tests
• CD4
• Amylase
• Bilirubin

 Optional* Viral load

 Resistance testing
*not available in Nigeria routinely at this time
Effectiveness of antiretrovirals
for PMTCT: Infection rates at 1
month
 Effectiveness depends on DURATION- how
early in pregnancy treatment started, and
on INTENSITY- how many drugs used
 No intervention: 20 % infected
 Single-dose NVP: 12 % infected
 ZDV from 28 weeks: 7 % infected
 2 drugs: 1-4 % infected
 HAART: <1 % infected
Thai randomized trial of PMTCT in non-
breastfeeding women & infants

Gestational Duration % Infants 90%

age ZDV of infant infected Confidence
started ZDV at 6 mo interval

28 3 days 4.7% 2.4-7.0

28 6 weeks 6.5% 4.1-8.9

35 3 days 10.5% 6.4-14.4

35 6 weeks 8.6% 5.6-11.6

 Summary of Efficacy of ARVs for PMTCT
Intervention (IP = intrapartum) % HIV+ at 1 month
None ~18-22%
Neonatal NVP or ZDV 13-21, 9.3-16.6
Neonatal ZDV/3TC or ZDV/NVP 14.2-15.3
Intrapartum/neonatal NVP 10.4-11.9
Intrapartum/neonatal ZDV 10-20
Intrapartum/neonatal ZDV/3TC 7.9-8.9
ZDV start 36-37 wk + IP + neonatal 9.6-15.1
ZDV start 35 wk + IP + neonatal 8.6-10.4
ZDV start 23-28 wk + IP + neonatal 4.3-8.3
ZDV/3TC start 36, 34, 23-32 wk 5.9, 2.8, 1.6
ZDV 28 wk + IP NVP and/or neonatal NVP 1.1-2.0
HAART 34 wk 3.6
Early HAART <1
Effectiveness of antiretrovirals
for PMTCT: Infection rates at 1
month
 Effectiveness depends on DURATION- how
early in pregnancy treatment started, and
on INTENSITY- how many drugs used
 No intervention: 20 % infected
 Single-dose NVP: 12 % infected
 ZDV from 28 weeks: 7 % infected
 2 drugs: 1-4 % infected
 HAART: <1 % infected
Caesarian delivery for
PMTCT
 Scheduled Caesarian delivery reduces
MTCT in infants at risk of HIV transmission
because mother is on no prophylaxis or
inadequate prophylaxis (ZDV monotherapy)
 No evidence of efficacy after onset labor
 Increased morbidity in women with HIV
 Under conditions where safe, scheduled
C/S can be performed, adequate ARV
prophylaxis should be feasible
THE NIGERIAN PMTCT
PROGRAM:HAART
1ST Line : ZVD+NVP+ Lamivudine
2nd Line : ZVD+Efaverenz+ Lamivudine

Outside tertiary centers:

NVP ± Lamivudine
ZDV ± Lamivudine
 Antiretrovirals in pregnancy
Drug Pros Cons
ZDV Lots of experience Anemia
3TC Lots of experience Resistance if not
HAART
D4T ? Mitochondrial toxicity
Do not use with DDI
DDI ? Mitochondrial toxicity
Do not use with D4T
ABC Potent Less experience
TDF ? Bone toxicity
 Antiretrovirals in pregnancy
Drug Pros Cons
NVP Experience Hepatic toxicity
Resistance if not HAART
EFV OK with rifampin ? 1st trimester teratogen
Resistance if not HAART
NFV Experience Not as potent as LPV/r
Well-tolerated
IDV/r ? Bilirubin
SQV/r Little experience; GI
LPV/r Potent GI intolerance
Safety of antiretrovirals in pregnancy-
maternal toxicity

 GI upset: most protease inhibitors (except nelfinavir)

 Anemia: zidovudine
 Hepatic toxicity
 Nevirapine, especially if CD4 >250 and female
 Other ARVs
 Hepatic steatosis, hepatic failure around term:
combination of D4T+DDI. Contraindicated in
pregnancy
 Glucose intolerance: PIs (except atazanavir)
 Resistance to ARVs after
prophylaxis against MTCT
 ZDV monotherapy from 2nd trimester: little resistance
 NVP single dose
 20-40% of mothers with detectable resistance
 46% of infants who fail prophylaxis have resistant virus
 ZDV from 28 weeks & in labor + single dose NVP- rate of NVP
resistance similar to single dose NVP without ZDV
 ZDV/3TC: 3TC resistance depending on duration (about 30%
after 3 months exposure)
 HAART regimens
 No resistance if full suppression achieved
 Varies according to regimen: NNRTI failure associated with rapid
resistance
Correlation Between Optimal Therapeutic
Response at 3 Months and Adherence to Protease
Inhibitor Therapy
100
90
% of patients with HIV

80
RNA <400 copies/mL

70 78
60
50
40
45
30
20 33 29
10 18
0
>95 90-95 80-90 70-80 <70
% of prescribed doses taken -- MEMS cap data

Paterson D, et al. Ann Intern Med. 2000;133:21-30.

GOAL: Take ARV meds exactly as prescribed so
there is enough medicine in blood at all times.
 THANK YOU