Towards Universal Access

1
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
2
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

3
Global inequities in the prevention of
mother-to-child 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 lt2 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

4
Timing of MTCT

• 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-breast-feeding 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..
• NNRTIs 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.

5
Comprehensive approach to prevent HIV infection
in infants

• Prevention of
• HIV in
• parents to be

Prevention of unintended pregnancies among
HIV-infected women
Prevention of transmission from an HIV-infected
woman to her infant
Care and support for HIV-infected women, their
infants and their families
6
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

7
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
resource-constrained settings.
8
The need for effective PMTCT Regimens for
resource-limited settings
WHO Paediatric HIV/AIDSin 2005 Global Estimate Sub- Saharan Africa Resource-Rich 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 lt2 in countries which
bear 0.6 of the global paediatric HIV burden
9
Evidence-based recommendations taking into
account scientific evidence and programmatic
experiences

• Recommendations based on evidence from
• randomized controlled trials
• high-quality scientific studies for
  non-treatment-related options
• observational cohort data,
• expert opinion where evidence is lacking or
  inconclusive

10
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-IP-PP regimen of AZT/3TC

11
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

12
Initiating ARV treatment in pregnant women
(based on clinical stage and availability of
immunological markers)
WHO clinical stage CD4 testing not available CD4 testing available
1 Do not treat (A-III) Treat if CD4 lt200 cells/mm3 (A-III)
2 Do not treat (A-III) Treat if CD4 lt200 cells/mm3 (A-III)
3 Treat (A-III) Treat if CD4 lt350 cells/mm3 (A-III)
4 Treat (A-III) Treat irrespective of CD4 cell count (A-III)
13
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 AZT starting at 28 wks
of pregnancy or as soon as thereafter Intrapartu
m Sd-NVP AZT/3TC Postpartum AZT/3TC for 7
days Infant Single dose NVP plus one week AZT
14
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 lt 4 wks of ART during
pregnancy, give 4 wks of infant AZT
15
Different approaches for using ARV prophylaxis to
prevent HIV infection in infants
Ranking Time of administration Time of administration Time of administration Time of administration
Ranking Pregnancy Labour Postpartum Postpartum
Maternal Infant
Recommended AZT (gt28 wks gestation) Sd-NVP 1 AZT/3TC AZT/3TC x7 days1 Sd NVP 1 AZT x 7 days 2

Alternative AZT (gt28 wks gestation) Sd-NVP Sd NVP AZT x 7 days 2
Minimum -- Sd-NVP AZT/3TC AZT/3TC x7 days Sd NVP
Minimum -- 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 lt 4 wks of AZT during pregnancy, 4 weeks
of infant AZT recommended
16
ARV prophylaxis for MTCT prevention among
pregnant women who have not received antenatal
ART or prophylaxis
Ranking Time of administration Time of administration Time of administration
Ranking Labour Postpartum 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
Minimum Sd-NVP AZT/3TC AZT/3TC x7 days Sd NVP
Minimum Sd-NVP Sd NVP
17
ARV prophylactic regimens for infants born to
HIV-positive women who have not received
antepartum or intrapartum ART or ARV prophylaxis
Ranking Time of administration
Ranking 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
18
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

19
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

20
Continuum of care for HIV-exposed 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

21
Guiding principles of the Guidelines
Integrated delivery of PMTCT interventions within
MCH services
WHO comprehensive strategic approach to the
prevention of HIV in infants and young children
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
Women's health as the overarching priority in
decisions about ARV treatment during pregnancy
22
KEY POINTS

• More than 90 transmission occurs in low resource
  countries
• MTCT can be reduced to low levelsgt2
• Increasing evidence of resistance to single dose
  Nevirapine
• New WHO guidelines for selection of appropriate
  drugs available