Zidovudine

Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein. Common side effects include headaches, fever, and nausea. Serious side effects include liver problems, muscle damage, and high blood lactate levels. It is commonly used in pregnancy and appears to be safe for the baby. ZDV is of the nucleoside analog reverse-transcriptase inhibitor (NRTI) class. It works by inhibiting the enzyme reverse transcriptase that HIV uses to make DNA and therefore decreases replication of the virus. Zidovudine was first described in 1964. It was approved in the United States in 1987 and was the first treatment for HIV. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is US$5.10 to $25.60 per month. As of 2015, the cost for a typical month of medication in the United States was more than $200. AZT is usually dosed twice a day in combination with other antiretroviral therapies. This approach is referred to as Highly Active Antiretroviral Therapy (HAART) and is used to prevent the likelihood of HIV resistance. AZT has been used for post-exposure prophylaxis (PEP) in combination with another antiretroviral drug called lamivudine. Together they work to substantially reduce the risk of HIV infection following the first single exposure to the virus. More recently, AZT has been replaced by other antiretrovirals such as tenofovir to provide PEP. AZT is now a principal part of the clinical pathway for both pre-exposure prophylaxis and post-exposure treatment of mother-to-child transmission of HIV during pregnancy, labor, and delivery and has been proven to be integral to uninfected siblings' perinatal and neonatal development. Without AZT, as many as 10 to 15% of fetuses with HIV-infected mothers will themselves become infected. AZT has been shown to reduce this risk to as little as 8% when given in a three-part regimen post-conception, delivery, and six weeks post-delivery. Consistent and proactive precautionary measures, such as the rigorous use of antiretroviral medications, cesarean section, face masks, heavy-duty rubber gloves, clinically segregated disposable diapers, and avoidance of mouth contact will further reduce child-attendant transmission of HIV to as little as 1–2%. During 1994 to 1999, AZT was the primary form of prevention of mother-to-child HIV transmission. AZT prophylaxis prevented more than 1000 parental and infant deaths from AIDS in the United States. In the US at this time, the accepted standard of care for HIV-positive mothers was known as the 076 regimen and involved 5 daily doses of AZT from the second trimester onwards, as well as AZT intravenously administered during labour. As this treatment was lengthy and expensive, it was deemed unfeasible in the Global South, where mother-to-child transmission was a significant problem. A number of studies were initiated in the late 1990s that sought to test the efficacy of a shorter, simpler regimen for use in ‘resource-poor’ countries. This AZT short course was an inferior standard of care and would have been considered malpractice if trialed in the US; however, it was nonetheless a treatment that would improve the care and survival of impoverished subjects. Most common side-effects include nausea, vomiting, acid reflux (heartburn), headache, cosmetic reduction in abdominal body fat, light sleeping, and loss of appetite. Less common side effects include faint discoloration of fingernails and toenails, mood elevation, occasional tingling or transient numbness of the hands or feet, and minor skin discoloration. Allergic reactions are rare.