E-DRUG: Antiretroviral drugs, genotoxicity, and adverse effects
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Dear E-druggers,
This link is to a report that the Norwegian Knowledge Centre for the
Health Services* has written by request from Norad, the Norwegian Agency
for Development Cooperation. Its main focus is on ARVs to reduce risk of
mother-to-child transmission of HIV.
http://www.kunnskapssenteret.no/filer/06_antiretroviral_drugs.pdf
* the Centre is organised under the Directorate for Health and Social
Affairs but is scientifically and professionally independent. It gathers
and disseminates evidence about the effect and quality of methods and
interventions within all parts of the health services.
Summary
Background: Antiretroviral drugs (ARVs) are used for treating
HIV-infected patients and also specifically for reducing the risk of
mother-to-child transmission of HIV in relation to pregnancy and
childbirth. In this report we review the consequences that have been
demonstrated for children following in utero exposure of these drugs. We
focus mainly on the groups of drugs that are known to be potentially
genotoxic (NRTIs). The risk of cancer development is the concern that is
most commonly related to genotoxicity, however we also review other
outcomes we believe to be important.
Methods: This is a summary of relevant research reports identified
through searches in several databases and reference lists in relevant
papers.
Main results: The research findings currently available do not indicate
an increased risk of adverse health outcomes related to in utero
exposures of ARVs. Zidovudine for preventing mother-to-child
transmission has not been associated with premature delivery, still
birth, low birth weight, birth defects or any other major adverse health
outcomes in the first year of life. Also, for ARV treatment during
pregnancy, no serious adverse effects have been demonstrated in the
young children. Despite this, some uncertainty remains regarding the
risk of short term adverse effects: The use of some drugs (NRTIs) may
lead to a slightly increased risk of mitochondrial disease. Protease
inhibitors may increase the risk of premature birth. Exposure to the
drug efavirenz during the first trimester may increase the risk of
malformations.
Other aspects: The long-term safety of the drugs, e.g. the risk of
cancer development, is not known due to the limited period of time the
drugs have been used. Studies are ongoing to monitor the long-term
consequences of in utero exposure to ARVs. It is also too early to
establish whether genotoxic effects from these drugs may be transferred
across generations. The possible risks linked to the use of ARVs in
pregnancy need to be weighed against the established benefits. For every
five HIV-positive pregnant women on ARVs, about one child less becomes
infected. The report is commissioned by Norad.
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Ms Kirsten Myhr, MScPharm, MPH
Head
RELIS Drug Info and ADR Monitoring Centre
Ulleval University Hospital
0407 OSLO, Norway
Tel: +47 23 01 64 11 Fax: +47 23 01 64 10
kirsten.myhr@relis.ulleval.no
myhr@online.no
(not involved in writing the report)