[pronut-hiv] WHO advises more complicated regimens and enhanced services to prevent mother-to-child transmission

["ProNut-HIV" <pronut-hiv@healthnet.org>]

Aidsmap
WHO advises more complicated regimens and enhanced services to prevent
mother-to-child transmission 

Theo Smart, Tuesday, August 08, 2006 

"All pregnant women eligible for antiretroviral therapy (ART) must
have access to it, and countries must adopt more efficacious
antiretroviral (ARV) regimens for preventing mother-to-child
transmission (PMTCT) among pregnant women who do not yet require ART"
- rather than simply using single dose nevirapine (sd-NVP) during
labour, according to new guidelines issued this week by the World Health
Organisation. 

The 'more efficacious' regimen for PMTCT for pregnant HIV-infected
women in resource-constrained settings who do not yet qualify for ART,
consists of AZT from 28 weeks of pregnancy (or as soon as possible
thereafter); during labour - AZT/3TC plus sd-NVP); and postpartum -
AZT/3TC for seven days for women and sd-NVP and AZT for one week for
infants. However, both ART and ARV regimens or is complicated
significantly depending upon local constraints, when HIV test results
become available for the pregnant woman and other maternal health
matters (see Recommended ART and ARV prophylaxis regimens below). 

But much more important than the precise ARV regimen used is the
recognition by the guidelines that, to be most effective, PMTCT services
must address maternal and child health holistically. These expanded
PMTCT services, beginning with the routine HIV testing of all pregnant
women and recent mothers, must be integrated into strengthened mother
and child health (MCH) services and HIV programmes throughout the
developing world in order to meet the goals of the recent Abuja Call to
Action: "the elimination of HIV infection in infants and young
children to pave the way towards an HIV-free and AIDS-free generation
across the globe." 

Background 
WHO first issued recommendations for the use of ARV drugs for PMTCT in
2000, and revised them in 2004 with the adoption of simplified and
standardised regimens. However, the implementation of national PMTCT
programmes has been slow, with less than 10% of pregnant women living
with HIV having access to such services according to the 2006 UN Report
on the Global AIDS Epidemic. 

This is despite the fact that, in many resource constrained settings,
PMTCT programmes have consisted of little more than screening pregnant
women for HIV and offering sd-NVP to the mother during labour and to the
child shortly after birth. But as capacity improves, programmes need to
offer much more than that according to the new guidelines. 

Since the original guidelines were published, considerable experience
that has been accumulated on how best to scale up PMTCT and ART
programmes. As a result, the revised guidelines now emphasise a more
comprehensive approach to the prevention of HIV infection in infants and
young children, which consists of four components: 

1. primary prevention of HIV infection; 
2. prevention of unintended pregnancies among women living with HIV; 
3. prevention of HIV transmission from mothers living with HIV to their
infants; 
4. care, treatment and support for mothers living with HIV, their
children and families. 

Enhancing mother and child health services 
The best way to mount this comprehensive attack upon MTCT is to
integrate a set of key interventions into enhanced MCH systems to make
sure "that women (i) have greater access to high-quality antenatal,
labour, delivery and postpartum care, including counselling and support
for infant feeding, and (ii) use existing services more frequently and
earlier in pregnancy than is currently the case." 

The first key intervention, the routine offer of HIV testing as early
in the pregnancy as possible, should be considered "an integral
component of essential care during pregnancy." Those who test negative
should be provided with services to keep them that way, especially while
they are pregnant or breastfeeding. For those women who test positive,
other HIV care (including access to CD4 cell monitoring) and support
services need to be integrated into MCH systems. 

But getting women to utilise the MCH system is a challenge in many
resource limited settings. For example, in some settings, many women do
not access antenatal care or do not utilise delivery/maternity services.
Thus, in order to make PMTCT programmes more effective, these MCH
services must be improved, and"the sociocultural factors, conditions
and circumstances that limit their uptake must be identified and
addressed. 

Preserving the mother's health 
The woman's health is the "overarching priority in decisions about
ARV treatment during pregnancy." The mother's continued well-being
is perhaps the most important determinant to the child's survival as
well. 

According to the guidelines, every pregnant woman who tests
HIV-positive must be assessed to determine whether she is eligible for
ART, by staging her HIV disease according to WHO's clinical staging
system, and, where available, monitoring her CD4 cell counts. "Efforts
should be made to include the CD4 cell count measurement in the
essential package of care for pregnant women." This is especially
important for women without symptoms of disease (WHO stage I or II) who
may however, have CD4 cell counts below 200. CD4 cell counts may also be
an important factor in deciding which ART regimen to use. 

WHO recommends that 

any woman with CD4 cell counts below 200 should be offered ART
regardless of clinical stage


women with stage III disease should be placed on ART if their CD4 cell
counts are below 350


all women with stage IV disease should be placed on ART irrespective of
the CD4 cell count

also, 

where CD4 cell tests are not available, all women with stage III and IV
disease should be put on ART.


In addition, women with HIV should be screened, and if necessary
treated for TB infection or offered isoniazid prophylaxis, be given
cotrimoxazole prophylaxis (if they are eligible), and provided with
counselling and care relating to nutrition, infant feeding and
psychosocial support. In areas where malaria transmission is common,
women should have access to insecticide-treated nets, case management
for malaria illness, if needed, or intermittent preventive treatment
with at least three doses of sulfadoxine-pyrimethamine or daily
cotrimoxazole prophylaxis. 

Recommended ART and ARV prophylaxis regimens 
Since the previous WHO guidelines were published, more evidence has
become available on the effectiveness of ART for PMTCT; the potential
for resistance following sd-NVP prophylaxis among mothers and its
implications for their future treatment options; better (though more
complicated) ARV prophylaxis regimens; and the safety of specific ARVs
in pregnant women. Furthermore, much more is known about how to use ARV
in women with co-morbidities such as tuberculosis or severe anaemia. 

As a result, the recommended ART or ARV prophylaxis varies
significantly depending upon the situation. 

ART 
Nevirapine/AZT/3TC is generally the preferred regimen for pregnant
women who need ART, and infants should be given AZT for 7 days after
birth. However, there are some situations where this guidance is a bit
tricky: 


Women with CD4 cell counts between 250-350. There are concerns about
nevirapine-related toxicity, including hepatitis, in this population.
The guidance recommends either using nevirapine and monitoring closely
over the first twelve weeks, or using either an efavirenz-, a protease
inhibitor- or a nucleoside-analogue based regimen, or delaying treatment
until CD4 cells fall below 250 (using ARV prophylaxis for PMTCT).
However, there are downsides to each alternative. 


Women with severe anaemia (Hb<7g/dl). AZT can cause or worsen anaemia,
so women should be offered a regimen substituting d4T or ABC for AZT
while receiving treatment for severe anaemia.


Women who require treatment for active TB. Since rifampicin and
nevirapine can negatively interact, efavirenz-based regimens are the
recommended first-line therapy for people with TB. However, since there
are concerns about possible effects to the foetus, efavirenz-based ART
should not be started until the second trimester of pregnancy. A
nucleoside analogue-based regimen is also an alternative, though they
are considered less potent.


Women on methadone. Nevirapine can decrease blood levels of methadone
so a 50-100% increases in the 

daily methadone doses may be required to treat opiate withdrawal.
Methadone could also increase AZT-related side effects. 

Women who are already on ART when they become pregnant should continue
what they are doing, unless, they are still in their first trimester and
on an efavirenz-based regimen. In such a case, nevirapine (at full dose)
should be substituted for efavirenz with close monitoring of women who
have CD4 cell counts above 250. Alternatively, a triple nucleoside or
PI-based regimen could be used. However, the guidelines stress that
efavirenz use in the first trimester is not an indication for abortion.


When a woman receives less than four weeks of ART, four weeks of AZT is
recommended for her infant rather than just one.


ARV prophylaxis 
As already noted, the recommended regimen for PMTCT is: 

antepartum - AZT from 28 weeks of pregnancy (or as soon as possible
thereafter)


intrapartum - AZT/3TC plus sd-NVP); and 


postpartum - AZT/3TC for seven days for women and for infants sd-NVP
(as soon as possible and up to 72 hours after birth) and AZT for one
week


The length of time that a women receives AZT will depend upon when she
is identified as being HIV-infected and guidance varies accordingly. 

If she receives at least four weeks of AZT, another recommendation
(given a lower grading for a weaker evidence base) is that sd-NVP may be
omitted in the mother (which may better preserve her future treatment
options). 


If she receives less than four weeks of AZT before delivery, the
infant's AZT dose should be extended to four weeks. 


Whenever sd-NVP is used for PMTCT, the mother should always receive
seven days of AZT/3TC to prevent resistance to nevirapine. If she
receives sd-NVP during a false labour, she should not be given a second
dose during labour as the second dose can greatly increase the
likelihood of reistance.


If delivery occurs less than two hours after taking sd-NVP, or the
mother receives no ARVs for PMTCT prior delivery, the infant should be
given sd-NVP immediately and AZT for four weeks.


The guidelines list the pros and cons of a number of alternative
regimens as well as their evidence-base. In addition, the guidelines
acknowledge that some settings "do not currently have the capacity to
deliver the recommended prophylactic regimen to prevent MTCT, [and that]
it may be necessary - as an absolute minimum - to implement the
single-dose (mother and infant) nevirapine regimen." However, this
should be considered "a short-term interim measure while steps are
being taken to enable more effective regimens to be delivered." 

Recommendations for women who have previously received sd-NVP for PMTCT

The guidelines stress that any woman who should be considered eligible
for nevirapine or efavirenz-based antiretroviral therapy, although
alternative regimens should perhaps be considered if ART is begun within
six months of exposure. 

Also, women who are pregnant can safely receive the same ARV regimen as
they used for a previous pregnancy without loss of activity (although
they should always be given the optimal recommended regimen). 

Recommendations on ART during breastfeeding 
Breastfeeding continues to be a major source of infection, undermining
the use of PMTCT during pregnancy. At the same time, breastfeeding is
usually the best option for feeding the child. 

The use of antiretroviral drugs by breastfeeding could possibly reduce
transmission, - and preliminary data show that this is indeed the case
in women taking ART for their own health. Nonetheless, WHO believes that
this is one area where the evidence base must be developed significantly
before making any firm recommendations. 

So the new guidelines state that the current WHO recommendations on
breastfeeding is still in effect -irrespective of whether a woman is
receiving ART. 

The guidance states that when replacement feeding is acceptable,
feasible, affordable, sustainable and safe, avoidance of all
breastfeeding by mothers living with HIV is recommended, and that,
otherwise, exclusive breastfeeding is recommended during the first
months of life and should then be discontinued as soon as feasible. 

Thus, when women are already on ART for their own health, the guidance
states that they should continue taking their regimen, (and still wean
their infants as soon as feasible), while for women who do not yet
qualify for ART, taking ARVs simply to reduce transmission through
breastfeeding is currently not recommended. 

This in the area where the guidance is most likely to change, since
recent studies suggest that infant HIV-free survival may be
significantly higher in women on ART - and that finding safe and
reliable replacement feeding can be virtually impossible in most
resource-constrained settings. 

The full guidelines document may be downloaded from the WHO website at
http://www.who.int/hiv/pub/guidelines/pmtct/en/index.html