To the surprise of researchers, the long-acting injectable antiretroviral cabotegravir can endure in the body for more than a year in some people, giving it an exceptionally long “tail,” (The tail of a drug refers to the period it lingers in the body after it’s discontinued.)

This raises questions about the drug’s toxicity as well as the likelihood that it may lead to drug resistance if individuals contract HIV after using it as pre-exposure prophylaxis (PrEP).

Researchers from the Phase IIa ÉCLAIR study presented findings at the HIV Research for Prevention 2016 conference in Chicago. The study of long-acting injectable cabotegravir’s use as pre-exposure prophylaxis (PrEP) against HIV included 127 men at low risk for the virus who were randomized to receive the drug or a placebo. First, they received four weeks of daily oral doses of the drug or a placebo; then, they received 800-milligram injections of long-acting cabotegravir or saline every 12 weeks, for a total of three injections.

The participants were treated for 41 weeks and followed for 81 weeks all told.

After the first injection, long-acting cabotegravir’s average half-life was 18 days. This figure rose to 40 days following the third injection. There was great variability between participants in how long the drug lingered. In some of the men, the drug fell below protective levels 24 weeks after the last injection. Others still had detectable drug a year after their last injection.

Individuals could be at risk of developing drug resistance to cabotegravir if following an injection of the long-acting drug as PrEP, they contract HIV at a point after the drug has dropped below a protective level but is still present enough in the body to give rise to a resistant strain of the virus. Researchers hope to look for ways to determine which individuals are more likely to have this long drug tail.

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