Transcript Towards Universal Access Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants in Resource-Limited Settings Recommendations for a Public Health Approach BASED.

Towards Universal Access
Antiretroviral Drugs for Treating Pregnant
Women and Preventing HIV Infection in
Infants in Resource-Limited Settings
Recommendations for a Public Health Approach
BASED ON WHO GUIDELINES
Dr. S.K CHATURVEDI
Dr. KANUPRIYA CHATURVEDI
OBJECTIVES:
 To understand the role of antiretroviral in
prevention of mother to child transmission
of HIV
 To understand the rationale behind the new
guidelines
 To know about the new WHO guidelines on
use of antiretroviral in prevention of mother
to child transmission of HIV(PMTCT)
 To be able to select appropriate
interventions for prevention of MTCT of HIV
Global inequities in the prevention of mother-tochild transmission of HIV
• More than 95% of paediatric HIV infection occurs in
resource-limited settings
• Virtual elimination of HIV infection in infants with MTCT
rates <2% in developed countries
• Low coverage and uptake in resource-limited settings:
• Less than 15% of pregnant women tested for HIV
• Less than 10% are offered ARV prophylaxis
• Less than 5% of HIV-infected women in need of treatment
are offered ART
Timing of MTCT
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HIV-1 transmission can occur during intrauterine, intrapartum,
and post-partum period. The estimates of timing of vertical
transmission differ between breast-feeding and non-breastfeeding population.
Various studies have shown that the estimates for intrauterine,
intrapartum, and postpartum period as ranging between 23-30
%, 45-50%, and 30-35 % among breast-feeding population
The efficiency of MTCT of HIV-2 was reported to be 1.2% when
compared to 24.7 % of HIV-1 that is almost 20 times lesser than
that of HIV-1..
NNRTI’s such as Nevirapine is not effective against reducing the
risk of transmission of HIV-2.
In breastfeeding populations, up to 44% of the infections can be
attributed to breastfeeding, depending on the duration of
breastfeeding and through risk factors such as presence of
mastitis, breast abscess and other local factors.
Comprehensive approach to
prevent HIV infection in infants
Prevention of
HIV in
parents to be
Prevention of
unintended
pregnancies
among HIVinfected women
Prevention of
transmission
from an HIVinfected
woman to her
infant
Care and support for HIV-infected women, their
infants and their families
SOURCE :WHO
WHO Guidelines for PMTCT
•
2000 Initial guidance
•
2004 Adoption of simplified and
standardized regimens
•
2005 Updated guidelines on the use of ARV
drugs for treating pregnant women
and preventing HIV infection in
infants
•
2006 Updated to incorporate new evidence
& align with the international
commitment to universal access to
HIV prevention, care, treatment &
and support services
A Public Health approach to PMTCT
services
The main purpose of adopting a public
health approach is to ensure access to
high-quality services at the population
level,
while striking a balance between the best
proven standard of care and what is
feasible on a large scale in resourceconstrained settings.
The need for effective PMTCT Regimens
for resource-limited settings
WHO Paediatric
HIV/AIDS
in 2005
Global
Estimat
e
SubSaharan
Africa
ResourceRich
Countries
Children Living with
HIV/AIDS
2.3
million
2.0 million
14,000
New Infant HIV
Infections
700,000
630,000
700
Deaths in Children
with HIV/AIDS
570,000
480,000
200
MTCT has been reduced to <2% in countries which bear 0.6% of the
global paediatric HIV burden
Evidence-based recommendations taking
into account scientific evidence and
programmatic experiences
60
50
80
No ART
70
40
HAART
60
Monotherapy
30
40
22.3%
19.4%
20
50
30
17.7%
17.5%
9.0%
10
6.6%
0
1990
MultiART
1991
1992
1993
1994
3.6%
1995
2.1%
1997
1998
Year of Enrollment
SOURCE:WHO
10
3.2% 3.0%
1996
20
0.9% 1.4% 1.6% 1.2%
1999
2000
2001
2002
0
2003+
% Receiving Therapy
• randomized controlled trials
• high-quality scientific studies
for non-treatment-related
options
• observational cohort data,
• expert opinion where evidence
is lacking or inconclusive
90
Transmission Rate per 100
Recommendations based on
evidence from:
100
Evidence from short course PMTCT
studies
 Efficacy of AZT alone or AZT/3TC regimens decreases
with breastfeeding, particularly with prolonged
breastfeeding
 In contrast, efficacy of sd-NVP less affected by
breastfeeding
 A combination regimen of AZT plus sd NVP is more
effective than single drug regimens in formula-fed and
breastfeeding populations
 AZT plus sd NVP is equally effective as a more
complex regimen of AZT/3TC + sd NVP and an AP-IPPP regimen of AZT/3TC
Evidence from short course PMTCT
studies
 Estimated 20-30% of pregnant women meet WHO
criteria for initiating ART for their own health
 Advanced disease, low CD4 are associated with higher
MTCT, even in women receiving short-course ARV
prophylaxis
 Risk of NVP resistance after sd-NVP, given alone or
with other ARVs, significantly higher in women with
indication of ART
 An AZT/3TC “tail” given at the time of Sd-NVP and for
a short time in the postpartum reduces development
of NVP resistance
Initiating ARV treatment in pregnant women
(based on clinical stage and availability of
immunological markers)
WHO clinical CD4 testing
stage
not available
CD4 testing available
1
Do not treat
(A-III)
2
Do not treat
(A-III)
3
Treat
(A-III)
Treat if CD4 <350
cells/mm3
(A-III)
4
Treat
(A-III)
Treat irrespective of
CD4 cell count
(A-III)
SOURCE WHO
Treat if CD4 <200
cells/mm3
(A-III)
Recommended regimens for treating pregnant
women and prophylactic regimen for infants
• Women, including pregnant women, who need ART for
their own health should receive this
• Women who do not need ART should be offered ARV
prophylaxis for MTCT prevention
The recommended prophylactic regimen is:
Mother:
Antepartum:
Intrapartum:
Postpartum:
AZT starting at 28 wks of pregnancy
or as soon as thereafter
Sd-NVP + AZT/3TC
AZT/3TC for 7 days
Infant:
Single dose NVP plus one week AZT
Recommended first-line ARV regimens for
treating pregnant women and prophylactic
regimen for infants
Mother
Antepartum AZT + 3TC + NVP twice
daily
Intrapartum AZT + 3TC + NVP twice
daily
Postpartum AZT + 3TC + NVP twice
daily
Infant
AZT x 7 days*
* If the mother receives < 4 wks of ART during pregnancy,
give 4 wks of infant AZT
SOURCE:WHO
Different approaches for using ARV prophylaxis
to prevent HIV infection in infants
Ranking
Time of administration
Pregnancy
Labour
Postpartum
Maternal
Recommended
Alternative
AZT
(>28 wks
gestation)
Sd-NVP 1
+
AZT/3TC
AZT
(>28 wks
gestation)
Sd-NVP
Minimum
Minimum
--
Sd-NVP
+ AZT/3TC
--
Sd-NVP
*
AZT/3TC x7 days1
Infant
Sd NVP 1
+
AZT x 7 days
Sd NVP
+
AZT x 7 days
AZT/3TC x7 days
2
2
Sd NVP
Sd NVP
1 If the woman receives at least 4 wks of AZT during pregnancy, omission of maternal NVP dose may be
considered; the infant NVP dose must be given immediately at birth; Infant: 4 wks of AZT instead of 1 wk;
and women do not require 7-day tail of AZT and 3TC.
2 If the mother receives < 4 wks of AZT during pregnancy, 4 weeks of infant AZT recommended
SOURCE:WHO
ARV prophylaxis for MTCT prevention among
pregnant women who have not received
antenatal ART or prophylaxis
Ranking
Time of administration
Labour
Postpartum
Maternal
Infant
Recommended
Sd-NVP +
AZT/3TC
AZT/3TC
x7 days
Sd NVP
+ AZT x 4 wks
Alternative
AZT + 3TC
AZT/3TC
x 7 days
AZT/3TC
x 7 days
AZT/3TC x7
days
Sd NVP
Minimum
Minimum
Sd-NVP +
AZT/3TC
Sd-NVP
Sd NVP
SORUCE:WHO
ARV prophylactic regimens for infants born to HIVpositive women who have not received antepartum
or intrapartum ART or ARV prophylaxis
Ranking
Time of administration
Infant Postpartum
Recommended
Sd-NVP + AZT x 4 weeks1
Alternative
Sd-NVP + AZT x 1 week
Minimum
Sd NVP
NVP administered immediately after birth, if possible within 12 hours after delivery, is likely to result in a larger
reduction in transmission than later initiation.
Data on added efficacy of 4 weeks of infant AZT in this situation limited
SOURCE:WHO
Special considerations in the
guidelines
 Pregnant women living with HIV who have
anaemia
 Pregnant women living with HIV who have
active tuberculosis
 Management of injecting drug-using pregnant
women living with HIV
 Pregnant women with HIV-2 infection
 Women with primary HIV infection during
pregnancy
Antiretroviral drugs for preventing HIV
postnatal transmission through
breastfeeding
• Current UN recommendations on HIV and infant feeding
remain valid, irrespective of whether a woman is receiving
ART
• Women receiving ART who are breastfeeding should
continue their ARV regimen
• The use of ARV drugs in the mother and/or infant solely to
prevent MTCT through breastfeeding is currently not
recommended
Continuum of care for HIVexposed children
 Immunization
 Growth monitoring
 Co-trimoxazole prophylaxis
 Postnatal longitudinal follow up, including diagnosis:
 Early diagnosis of HIV infection
 Nutritional support as necessary
 HIV/AIDS care, treatment and support services
Guiding principles of the Guidelines
WHO comprehensive strategic approach
to the prevention of HIV in infants and
young children
Integrated delivery of PMTCT
interventions within MCH services
A public health approach
for increasing access
to PMTCT services
Necessity for highly effective ARV
regimens for eliminating HIV infection in
infants and young children
SORUCE:WHO
Women's health as the overarching priority
in decisions about ARV treatment during
pregnancy
KEY POINTS
 More than 90% transmission occurs
in low resource countries
 MTCT can be reduced to low
levels>2%
 Increasing evidence of resistance to
single dose Nevirapine
 New WHO guidelines for selection of
appropriate drugs available