Antiretroviral drugs, genotoxicity, and adverse effects
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A summary of research findings related to clinically important adverse effects from in utero exposure to antiretroviral (ARV) medication.
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The Norwegian Agency for Development Cooperation (Norad) requested a summary of research findings related to clinically important adverse effects from in utero exposure to antiretroviral (ARV) medication. The request was motivated by concerns that have been raised related to genotoxic properties of some ARVs.
In this report we review the consequences that have been demonstrated for children following in utero exposure of ARVs. We focus mainly on the groups of drugs that are known to be potentially genotoxic. 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.
We identified two high quality systematically developed literature reviews and several traditional reviews of lower methodological quality.
The research findings currently available do not indicate an increased risk of adverse outcomes related to in utero exposure 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 years of life after in utero exposure. Also, for ARV-treatment during pregnancy, no serious adverse effects have been demonstrated in the young children.
Despite this, some uncertainty remains, also regarding the risk of short term adverse effects after in utero exposure:
- The use of some drugs (nucleoside reverse transcriptase inhibitors) may lead to a slightly increased risk of mitochondrial disease
- Protease inhibitors may increase the risk of premature birth
- Exposure to the drug efivarenz during the first trimester may increase the risk of malformations
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. However, as of today there are no documented examples in humans of any drug-induced genetic changes being transmitted to unexposed offspring.
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.