NEW WHO GUIDELINES ON PMTCT

Article image ANTIRETROVIRAL DRUGS FOR TREATING PREGNANT WOMEN AND PREVENTING HIV INFECTION IN INFANTS: GUIDELINES ON CARE, TREATMENT AND SUPPORT FOR WOMEN LIVING WITH HIV/AIDS AND THEIR CHILDREN IN RESOURCE-CONSTRAINED SETTINGS.

Mother-to-child transmission (MTCT) is the most important source of HIV
infection in children. In 2001, the United Nations General Assembly
Special Session on HIV/AIDS committed countries to reduce the
proportion of infants infected with HIV by 20% by 2005 and by 50% by 2010.
Achieving this target urgently requires an increase in access to integrated and
comprehensive programmes to prevent HIV infection in infants and young
children. Such programmes consist of interventions focusing on primary
prevention of HIV infection among women and their partners; prevention
of unintended pregnancies among HIV-infected women; prevention of HIV
transmission from HIV-infected women to their children; and the provision of
treatment, care and support for women living with HIV/AIDS, their children and
families.

WHO convened a Technical Consultation on Antiretroviral Drugs and the
Prevention of Mother-to-Child? Transmission of HIV Infection in Resource-limited
Settings in Geneva, Switzerland on 5–6 February 2004. Scientists, policymakers,
programme managers and community representatives reviewed the
most recent experience with programmes and evidence on the safety and
effi cacy of various antiretroviral (ARV) regimens for preventing HIV infection in
infants. This information was reviewed in the context of the rapid expansion
of ARV treatment in resource-constrained settings using standardized and
simplifi ed drug regimens. Prior to the Technical Consultation, a draft set of
recommendations had been issued for public comment.

Women may receive ARV drugs during pregnancy as part of potent combination
regimens used to treat their HIV infection or as prophylaxis to prevent HIV
infection in infants. ARV treatment for women benefi ts their health but also
substantially reduces the risk of MTCT. All efforts should be made to ensure that
all women who require ARV treatment have access to it.

Therapeutic decisions relating to ARV treatment for women should be based
on their need and eligibility for such treatment. However, ARV regimens for
women of childbearing age should be selected considering the possibility of
a planned or unintended pregnancy and considering that ARV drugs may be
taken in the fi rst trimester of pregnancy, before a pregnancy is recognized.

Short courses of ARV drugs started in late pregnancy or during labour reduce
the risk of in utero and peripartum HIV transmission two- to three-fold; in 2000,
WHO recommended that they be included in programmes to prevent MTCT. At
that time, the recommended regimens included zidovudine (ZDV) alone or in
combination with lamivudine (3TC) and nevirapine (NVP). The simplest regimen
consisted of single-dose NVP at the onset of labour plus a single dose for the
infant soon after birth. Programmes to prevent MTCT based on this regimen
have been shown to be feasible and acceptable. There have been several years
of experience in implementing such programmes. In addition, the results of
research on other ARV regimens for preventing MTCT have become available
since WHO issued recommendations in 2000.

The effi cacy of ZDV plus single-dose maternal and infant NVP has been
examined in several settings. Although directly comparing studies is diffi cult, a
combination regimen of ZDV plus single-dose maternal and infant NVP is more
effi cacious than single drug regimens and, in general, longer regimens are more
effi cacious than shorter regimens.

Although triple-combination regimens are widely used in industrialized
countries for preventing MTCT in women who do not yet require ARV treatment
for their own health, their safety and effectiveness have not been assessed in
resource-constrained settings. There is serious concern about risk to the woman
if possible toxicity cannot be carefully monitored.

Information on the safety of various ARV regimens shows that short-course
regimens are, in general, well tolerated, with few mild and transient side-effects
for the woman and her infant. There is more concern about the safety of ARV
drugs taken by pregnant women for extended periods, especially those who do
not yet require ARV treatment. Among women who require ARV treatment for
their HIV disease, the benefi ts to the women’s health outweigh the known and
theoretical adverse effects.

Drug resistance induced by short-course regimens to prevent MTCT that do
not fully suppress the virus has been a concern since early 2000. As MTCTprevention
and ARV-treatment programmes expand and programmes to
prevent MTCT identify women needing treatment (either immediately or at
a later time), potential resistance has become a far greater concern. Viral
resistance has also been detected in HIV-infected infants exposed to shortcourse
ARV regimens. Resistance to NVP develops rapidly and has been noted
following single doses of NVP. ZDV resistance usually only emerges after several
months of partly suppressive therapy. Resistance to 3TC has not been detected
when it has been used in combination with ZDV for short periods but has
been detected following longer periods of exposure (more than four weeks).
The clinical consequences of viral resistance following short-course MTCT prophylaxis are unclear. The concern about resistance should be balanced with the programmatic simplicity and practicality of the single-dose NVP regimen compared with other regimens and the urgent need to expand programmes to prevent MTCT.

Successful programmes to prevent MTCT are complex interventions, of which
the ARV regimen is but one component. Although regimens based on ZDV
plus single-dose maternal and infant NVP are highly effi cacious, providing
twice-daily ARV prophylaxis to pregnant women from 28 weeks of pregnancy
increases the burden on programmes and on the women who participate. ARV
prophylaxis using single-dose maternal and infant NVP remains a practical
alternative when regimens based on ZDV plus single-dose maternal and infant
NVP are not acceptable or feasible. Progress in implementing programmes to
prevent MTCT based on single-dose maternal and infant NVP or other shortcourse
regimens should not be undermined.

Although considerable progress has been made in understanding the factors
associated with HIV transmission during breastfeeding, reliably preventing
transmission during this period remains a challenge in places where infant
formula cannot be safely provided. The potential role of infant and/or
maternal ARV prophylaxis in preventing postnatal transmission of HIV is being
investigated.

In the light of the scientifi c evidence available and the programmatic experience
accumulated, the participants at the Technical Consultation recommended
specifi c ARV regimens according to different clinical situations. These guidelines
are based on those recommendations and expert opinion where evidence was
lacking. Key recommendations in the guidelines are as follows.

1. Women who need ARV treatment for their own health should receive it
in accordance with the WHO guidelines on ARV treatment. The use of
ARV treatment, when indicated, during pregnancy substantially benefi ts
the health of the woman and decreases the risk of HIV transmission to the
infant.

2. HIV-infected pregnant women who do not have indications for ARV
treatment, or do not have access to treatment should be offered ARV
prophylaxis to prevent MTCT using one of several ARV regimens known to
be safe and effective:
◗ ZDV from 28 weeks of pregnancy plus single-dose NVP during labour
and single-dose NVP and one-week ZDV for the infant. This regimen is
highly effi cacious, as is initiating ZDV later in pregnancy.
◗ Alternative regimens based on ZDV alone, short-course ZDV + 3TC or
single-dose NVP alone are also recommended.

3. Although expanding access to programmes to prevent MTCT presents
many challenges and single-dose maternal and infant NVP is the simplest
regimen to deliver, programmes should consider introducing more complex
ARV regimens where possible. The expansion of programmes to prevent
MTCT using single-dose NVP should not be hindered while necessary
improvements in health systems are taking place to enable more complex
ARV regimens to be delivered.

WHO will regularly review the evidence base for these guidelines and will issue
updated recommendations when warranted by new information.

Full document available at: www.who.int/reproductive-health/rtis/docs/arvdrugsguidelines.pdf