1. Dr Tin Tin Sint Department of HIV/AIDS World Health Organization
WHO guidelines on use of antiretroviral drugs for the prevention of mother-to-child transmission of HIV
Dr Tin Tin Sint
Department of HIV/AIDS
World Health Organization

2. Mother-to-child transmission of HIV
Without any intervention 15%-45% of infants born to mothers living with HIV will become infected
Virtual elimination of MTCT have been achieved in developed countries (<2%)
A comprehensive package is needed:
Primary prevention in parents-to-be
Prevention of unintended pregnancies among HIV-infected women
Prevention of HIV transmission from women living with HIV to their infants
Provision of appropriate treatment, care and support to all those infected and affected
Women account for approximately half of all adults living with HIV/AIDS – 15.4 out of 33.2 million
90% of all HIV-infected pregnant women in low- and middle-income countries live in 20 high burden countries, all but on of these are in sub-Saharan Africa (list of the 20 countries)
Every day around 1200 children under the age of 15 years get newly infected with HIV and MTCT is the cause in more than 90% of cases
Without any intervention 15-45% of infants will acquire the virus from the infected mother depending on the duration of breastfeeding (5-10% during pregnancy, 10-20% during labour and delivery, and 5-20% through breastfeeding)
However, the transmission rate has been reduced to around 2% in developed countries using specific interventions, and equally around 5% in resource-limited setting where breastfeeding is the norm
WHO and other UN agencies recommend a four element comprehensive approach to maximize the reduction in number of women living with HIV and infants being infected through MTCT
We will in this session focus on intervention related to preventing HIV transmission from infected mothers, with a focus on antiretroviral durgs

3. The evolution of interventions and national programmes
Research on use of ARV for PMTCT started in the '90s with reported efficacy of various regimen in the late '90s (Shaffer et al.; Wiktor et al.; Guay et al.)
Several regimens using mono-, dual-, or combination prophylaxis found to be efficacious
Pilot projects to define implementation feasibility carried out in resource-limited settings
Recent scale up of pilot projects to national programmes (88 out of 109 reporting countries)

4. Current WHO 2006 recommendations: HIV testing and counselling
All pregnant women should be offered HIV testing and counselling as part of routine ANC
First step in providing targeted interventions including PMTCT
Using provider-initiated testing and counselling should be the norm and greatly increases access to the services
Rapid testing with same day result should enable more clients to be aware of their own serostatus and therefore increases uptake of services
Only, about 18% of total estimated number of pregnant women in low- and middle-income countries received an HIV test (2007)

5. Percentage of pregnant women in low- and middle-income countries receiving an HIV test (2004-2007)
Source: Universal Access Report, 2007

6. Current WHO 2006 recommendations: screening for ART eligibility
When a pregnant woman is identified with HIV eligibility for ART must be assessed using clinical staging and/or CD4 cell count, and ART provided as necessary
High viral load and low CD4 means high transmission
Women with low CD4 are those who needs ART
Providing ART to pregnant women in need will address the health issue of the mother and in addition significantly reduce MTCT
Only 12% of pregnant women identified as HIV-positive during ANC were assessed for eligibility (2007)

7. Eligibility criteria 1 2 3 4 WHO clinical stage
CD4 testing not available
CD4 testing available 1
Do not treat
(A-III)
Treat if CD4 <200 cells/mm3 2 3
Treat
Treat if CD4 <350 cells/mm3 4
Treat irrespective of CD4 cell count (A-III)

8. AZT + 3TC + NVP twice daily
Recommended regimens for treating pregnant women and prophylactic regimen for infants
For women, including pregnant women, who need ART for their own health:
Mother
Antepartum
AZT + 3TC + NVP twice daily
Intrapartum
Postpartum
Infant
AZT x 7 days*
* If the mother receives < 4 wks of ART during pregnancy, give 4 wks of infant AZT

9. Combination ARVs are more effective and reduces resistance
Current WHO 2006 recommendations: more efficacious regimens for prophylaxis
If not eligible for therapy, use more efficacious prophylactic regimens
Combination ARVs are more effective and reduces resistance
Risk of transmission at 18 months
20% with no ARV (WITS)*
10.4% with AZT monotherapy (WITS)*
3.8% with dual-ARV (WITS)*
1.2% with triple-ARV (WITS)*
15.7% with single-dose nevirapine vs. 25.8% with AZT (HIVNET 012)**
*Cooper E et al. JAIDS **Jackson JB et al. Lancet 2003

10. The recommended prophylactic regimen is:
Recommended regimens for treating pregnant women and prophylactic regimen for infants
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
Intrapartum Sd-NVP + AZT/3TC
Postpartum AZT/3TC for 7 days
Infant Single dose NVP plus one week AZT*
* If the mother receives < 4 wks of ART during pregnancy, give 4 wks of infant AZT

11. More efficacious regimens
Combination prophylaxis regimen lowers transmission rate
AZT given for a longer period during pregnancy is more efficacious
Nevirapine is important in preventing early postnatal transmission through breastfeeding due to its long half-life
Addition of 3TC is to prevent resistance to nevirapine (for future treatment options)

12. Time of administration
Different approaches for using ARV prophylaxis to prevent HIV infection in infants
Ranking
Time of administration
Pregnancy
Labour
Postpartum
Maternal
Infant
Recommended
AZT (>28 wks gestation)
Sd-NVP +
AZT/3TC
AZT/3TC x 7 days
Sd NVP + AZT x 7 days
Alternative
Minimum --
+ AZT/3TC
Sd NVP

13. Distribution of ARV regimens for PMTCT (2007)
Source: Universal Access Report, 2007

14. Time of administration
ARV prophylaxis for PMTCT 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 x 7 days
Sd NVP + AZT x 4 wks
Alternative
AZT + 3TC
AZT/3TC x 7 days
Minimum
Sd NVP
Sd-NVP

15. Time of administration
ARV prophylaxis for infants born to HIV-positive women who have not received 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
1 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

16. Setting priorities
The health of the mother is the first priority
Identify most effective interventions that can be provided to a maximum number of women
Quality of services should not be neglected while scaling up
Improved child survival should be the outcome

17. Review of evidence
WHO systematically reviews available evidence and programme performance, and will convene an expert consultation in late 2008
Department of HIV/AIDS
Department of Child and Adolescent Health and Development
Department of Reproductive Health and Research