Animal studies

Tenofovir was the first drug to be studied as possible PrEP, partly because it is relatively non-toxic, is taken once a day, has quite a long half-life and is relatively resistance-proof.

But it is also because in 1995, while the drug was still called PMPA, a research team led by Che-Chung Tsai had the foresight to see if this antiretroviral could prevent, as well as treat, HIV.¹ Tsai gave 25 rhesus macaques daily doses of tenofovir for a month. He gave the drug at four different times relative to injecting them with Simian Immunodeficiency Virus (SIV). He gave ten of them PEP five or 24 hours after infection. But he also gave 15 of them PrEP, 24 or 48 hours before infection.

None of the macaques were infected, compared with ten in the control group, who all became infected. The investigators looked for laboratory and clinical evidence of SIV infection for more than a year but found none, even in lymph nodes. The study suggested that PrEP might be a very effective prevention measure. 

Subsequent animal studies produced much more mixed results. Ten years later, at a study presented to the 12^th Conference on Retroviruses and Opportunistic Infections (CROI), Subbarao and colleagues presented a study in which tenofovir delayed, but did not prevent, infection.²

The researchers gave twelve rhesus macaques a daily dose of tenofovir, a weekly dose or a placebo. They mimicked human anal sex more accurately than Tsai had done. He had injected his macaques with a single massive dose of SIV, but Subbarao introduced SIV repeatedly as a weekly rectal inoculation. Subbarao’s rectal inoculation contained three to five times more viral particles than the maximum normally recorded in people who have acute HIV infection, and 25 to 60 times more than the usual viral load in chronic infection.

In this study, tenofovir delayed, but did not stop, infection in any monkey. Half the non-treated monkeys were infected after the first inoculation of SIV, whereas it took seven inoculations to infect half the treated monkeys. However, all the monkeys were infected after 15 inoculations, and all but one after 12. The researchers said that the results suggested that the drug “delayed infection by 85%” – but it did not prevent it.