Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV

Infection in Infants in Resource-Limited Settings

René Ekpini

Towards Universal Access

Recommendations for a Public Health Approach

Global inequities in the prevention of mother-to-child

transmission of HIV

• More than 90% of paediatric HIV infections occurs in resource-limited settings

• Virtual elimination of HIV infection in infants with MTCT rates <2% in developed countries bearing only 0.6% of global paediatric burden

• 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

International commitments to re-energize the PMTCT agenda

The UNAIDS universal access initiative

" …with the aim of an AIDS-free generation in Africa, significantly reducing HIV infections and working with WHO, UNAIDS and other international bodies to develop and implement a package for prevention, treatment and care, with the aim of as close as possible to universal access to treatment for all those who need it by 2010".

The Abuja call to action: towards an HIV-free and

AIDS-free generationCalled upon governments, development partners, civil society and private sector to join this Call to Action, and move swiftly towards supporting measures needed to eliminate HIV in infants and young children and clear the way for a worldwide HIV-free and AIDS-free generation

Goal: elimination of HIV infection in infant and young children to pave the way towards an HIV-free and AIDS-free generation

Objective of the Guidelines

• Provide guidance to assist national ministries of health in the selection and the provision of ART and ARV prophylaxis for women and their infants in the context of PMTCT

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, or expert opinion where evidence is lacking or inconclusive

Recommendations for 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 <200 cells/mm3

(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)

WHO Guidelines implementation: Cote d’Ivorie results - Tonwe-Gold B et al, 12th CROI, Boston, MA 2005 (abs 785)

ART indicated:HAART

ART not indicated:AZT/3TC+Sd-NVP

No. deliveries 101 138

Twins 2 4

Neonatal death 2 2

Stillbirth 4 6

Live birth 93 126

Not tested (<4-6 wks)

11 21

# tested at 4-6 wks 82 105

# infected at 4-6 wks

2 4

% infected at 4-6 wks (95% CI)

2.4% (0.3-8.5%)

3.8% (1.0-9.5%)

p=0.70

Conclusions from short-course ARV prophylaxis studies -1-

• 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 AZT/3TC regimen

Conclusions from short-course ARV prophylaxis studies -2-

• Estimated 20-30% of pregnant women meet WHO criteria for initiating ART for their own health

• Advanced disease, low CD4 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

Recommended regimens for treating pregnant women and

prophylactic regimen for infants

• Women, including pregnant women, who need ART for their own health should receive it

• 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 thereafterIntrapartum: Sd-NVP + AZT/3TCPostpartum: 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

Different approaches for using ARV prophylaxis to prevent HIV infection in

infants

* 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

Ranking Time of administration

Pregnancy Labour Postpartum

Recommended AZT (>28 wks gestation)

Sd-NVP 1

+ AZT/3TC

Maternal: AZT/3TC x7 days 1

Infant: Sd NVP 1 + AZT x 7 days 2

Alternative AZT (>28 wks gestation)

Sd-NVP Infant: Sd NVP + AZT x 7 days 2

Minimum--

Sd-NVP + AZT/3TC

Maternal: AZT/3TC x7 daysInfant: Sd NVP

Minimum -- Sd-NVP Infant: Sd NVP

ARV prophylaxis for MTCT prevention among pregnant women who have not received antenatal ART or prophylaxis

Ranking Time of administration

Labour Postpartum

Recommended Sd-NVP + AZT/3TC

Maternal: AZT/3TC x7 days

Infant: Sd NVP + AZT x wks

Alternative AZT + 3TC Maternal: AZT/3TC x7 daysInfant: AZT/3TC x 7 days

Minimum Sd-NVP + AZT/3TC

Maternal: AZT/3TC x7 daysInfant: Sd NVP

Minimum Sd-NVP Infant: Sd NVP

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

Postpartum

Recommended Infant: Sd-NVP + AZT x 4 weeks1

Alternative Infant: Sd-NVP + AZT x 1 week

Minimum Infant: 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

Special considerations

• 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

Guiding principles of the Guidelines

WHO comprehensive strategic approach to the prevention of HIV in infants and young children

Women's health as the overarching priority in decisions about ARV treatment during pregnancy

Women's health as the overarching priority in decisions about ARV treatment during pregnancy

Integrated delivery of PMTCT interventions within MCH services

Integrated delivery of PMTCT interventions within MCH services

Necessity for highly effective ARV regimens for eliminating HIV infection in infants and young children

Necessity for highly effective ARV regimens for eliminating HIV infection in infants and young children

A public health approach for increasing access

to PMTCT services

Scaling up national PMTCT programmes

Government leadership and commitment to mobilizing and allocating resources

A national scale up plan built around decentralization and integration

Adoption of standards and simplification of approaches to service delivery

Health system strengthening for effective delivery of services

Engaging and supporting communities to alleviate stigma and discrimination

A glimmer of hope

for an HIV-free and AIDS-free

Generation