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Commonly Prescribed HIV Drug May Cause Memory Loss

Researchers at Johns Hopkins recently reported that treatment with the antiretroviral drug efavirenz may contribute to cognitive decline in HIV-infected patients. According to a news release from Johns Hopkins Medicine, “Efavirenz is known to be very good at controlling the virus and is one of the few that crosses the blood-brain barrier and can target potential reservoirs of virus in the brain. Doctors have long believed that it might be possible to alleviate cognitive impairment associated with HIV by getting more drugs into the brain, but researchers say more caution is needed because there may be long-term effects of these drugs on the brain.”
The neurocognitive decline that affects a large percentage of HIV patients has long been thought to be a function of the disease itself. But this research suggests that some antiretroviral treatments themselves may contribute to the problem.
In the release, Norman J. Haughey, PhD, associate professor of neurology at the Johns Hopkins University School of Medicine, said “we need to be very careful about the types of anti-retrovirals we prescribe, and take a closer look at their long-term effects. Drug toxicities could be a major contributing factor to cognitive impairment in patients with HIV.”
In study results published in the Journal of Pharmacology and Experimental Therapeutics, Haughey and colleagues examined the effects of efavirenz and the efavirenz metabolites 7-hydroxyefavirenz (7-OH-EFV) and 8-hydroxyefavirenz (8-OH-EFV) on “calcium, dendritic spine morphology, and survival” in primary neurons cultured in the lab.
They reported that efavirenz and its metabolites “each induced neuronal damage in a dose-dependent manner,” with 8-OH-EFV proving to be “at least an order of magnitude more toxic than EFV or 7-OH-EFV, inducing considerable damage to dendritic spines.” They also reported that 8-OH-EFV “evoked calcium flux in neurons” and that “concentrations of EFV and 8-OH-EFV in the cerebral spinal fluid of HIV-infected subjects taking EFV were within the range that damaged neurons in culture.” The authors wrote that these findings “demonstrate that the 8-OH metabolite of EFV is a potent neurotoxin and highlight the importance of directly determining the effects of antiretroviral drugs and drug metabolites on neurons and other brain cells.”
The good news for HIV-infected patients is that, according to the Hopkins Medicine news release, “a minor modification in the drug’s structure may be able block its toxic effects but not alter its ability to suppress the virus.” One of the study authors also reported that it is possible to modify the drug “to prevent it from metabolizing into 8-hydroxyefavirenz while maintaining its effectiveness as a tool to suppress the HIV virus.”

Further Reading
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