E-drug: PMTCT through ARV treatment of infants
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[At a time when the safety of nevirapine for prevention of mother to
child transmission (PMTCT) of HIV infection is being questioned in
one part of Africa, a study in another part of Africa shows that it
is possible to use nevirapine in infants for PMTCT. Wendy Holmes of
the Burnet Institute has provided some thoughts on the implications
of this study. BS]
Some thoughts on the implications of the SIMBA study findings
Wendy Holmes
Womens' and Children's Health Specialist
Centre for International Health Macfarlane Burnet Institute for
Medical Research and Public Health
P O Box 2284 Melbourne 3001 Australia
holmes@burnet.edu.au
Vyankandondera J, Luchters S, Hassink E, Pakker N, Mmiro F, Okong
P, Kituuka P, Ndugwa C, Mukanka N, Beretta A, Imperiale M, Loeliger
E, Giuliano M. Lange J. Reducing risk of HIV-1 transmission from
mother to infant through breastfeeding using anti-retroviral
prophylaxis in infants (Stopping Infection from Mother-to-child via
Breastfeeding in Africa (SIMBA) study). Second International Aids
Society Conference on HIV Pathogenesis and Treatment. Paris, 16 July
2003.
The Simba study enrolled HIV positive pregnant women and followed up
397 infants in two hospitals in Kigali, Rwanda, and Kampala, Uganda.
The pregnant women were given a short combined course of zidovudine
(AZT) and didanosine (DDI) from 36 weeks to one week after delivery,
and the infants were given, from birth, either lamivudine (3TC) or
nevirapine during the full breastfeeding period plus an additional
four weeks after weaning. Mothers were counselled to breastfeed
exclusively and to stop breastfeeding between 3 and 6 months. Median
duration of breastfeeding was 100 days. About 90% breastfed
exclusively.
At the end of the study, HIV transmission occurred in 1.1% of infants
on 3TC and 0.6% of those on nevirapine. The researchers compared
this to a background risk from breastfeeding of around 15%. This
study uses different drugs for the mothers and the babies in order to
prevent the risk of nevirapine resistance in the mothers after the
first baby.
Implications:
It is important that we now have a study that shows it is possible
for babies to receive prophylactic ARV drugs during lactation, and
that these drugs are able, for some months, to protect against
postnatal transmission of HIV.
The study also demonstrated, as have other studies, that it is
possible to achieve very high rates of exclusive breastfeeding
through supportive counselling.
However we should note that several factors may have contributed to
the reduction in transmission of HIV in this study:
� The mothers took a combination of ARVs for one week post-partum
when we know the risk of postnatal transmission is greatest.
� The babies were exclusively breastfed, which may reduce risk of
postnatal transmission, (and possibly even 'mop up' some of the
transmission that occurs at delivery).
� Because the babies breastfed exclusively there is likely to have
been a lower incidence of breast problems (engorgement, sub-clinical
mastitis, cracked nipples) that we know contribute greatly to
postnatal transmission .
� The 3TC or nevirapine given to the babies during the period of
lactation are also likely to have protected the babies against
infection.
Some questions we need to ask:
� Why was median breastfeeding duration briefer than planned?
� How difficult did the mothers find the prophylactic regimen?
� How good was compliance with the regimen?
� What were the characteristics of the mothers, especially in terms
of viral load and immune status? (The "background risk" for
comparison should not be assumed to be 15%. This is the additional
risk of MTCT of HIV with mixed feeding for 24 months, when mothers
have received no anti-retroviral prophylaxis. But these mothers
received ARVP, and the babies were exclusively breastfed, for, on
average, only 3 - 4 months. It is difficult to assess the additional
benefit from the breastfeeding intervention since the 'background
risk' depends on many variables, most importantly the maternal viral
load. It is important to remember that in the Bangkok ZDV short
course trial, and in the PETRA study, the placebo group had a
transmission rate much lower than had been expected.)
Even though the cost of the drugs may be relatively low, the services
that need to be established to enable this intervention to be
implemented successfully at scale are not cheap. This is a complex
regimen, involving three different ARVs - there are significant
logistical implications, in terms of ordering, storage and security.
The complexity also raises potential problems in training health care
workers in the necessary protocols, and giving them the ability to
answer the different questions that will arise. Counsellors will
also need careful training to enable them to communicate clearly with
mothers, fathers and families. Care needs to be taken to ensure that
the nevirapine syrup is given only to the baby and not taken by other
members of the family who may have HIV-related illness.
National policy makers will need to consider the implications for
general resistance in future with an increased number of ARV drugs
available in public hospital settings. At the same conference Dr.
Charles Boucher presented worrying findings from the "Combined
analysis of resistance transmission over time of chronically and
acute infected HIV patients in Europe" study, which tested 1,633
patients from 17 European countries who had just been diagnosed with
HIV and who had not yet been treated for it. About 9.6% of the
patients were resistant to at least one of the three types of
antiretroviral drugs that suppress the virus. Resistance to
nucleoside reverse-transcriptase inhibitors was found in 6.9%;
resistance to non-nucleoside reverse-transcriptase inhibitors in 2.6
%; and resistance to protease inhibitors in 2.2%.
For those babies who become infected with HIV in utero or during
labour, their HIV is likely to develop resistance to nevirapine,
reducing their future treatment options.
Establishing sound systems for the training, supervision and support
of HIV and infant feeding counselors remains a priority. This is a
rapidly changing field and there is a need for mechanisms to
disseminate new findings and their implications to health care
professionals, public health officials and counsellors.
Changing drug regimens in existing PMTCT programs has considerable
implications for staff, and for mothers and their families.
Counsellors need to be consulted about their experiences. In
general, mothers have been pleased when their babies have received
medicine in the nevirapine regimen, in comparison with the short
course zidovudine regimen in which the baby did not receive a drug.
There is also potential for better post-natal follow-up of both
mother and baby when mothers need to return for supplies of
nevirapine for their baby.
Access the current issue of the Essential Drugs Monitor No.32 at
http://www.who.int/medicines/mon/mon32.shtml
Access archives of past EDM issues at
http://www.who.int/medicines/information/infmonitor.shtml
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