Prevention of rectal transmission of SIV in macaques using FTC with tenofovir: FTC has independent protective effect even as monotherapy

Walid Heneine from CDC Atlanta, presented results showing that adding FTC to tenofovir provided greater protection against SIV infection that standard dose tenofovir. A separate study with FTC monotherapy found an independent protective effect.

Six rhesus macaques were injected subcutaneously with 22 mg TDF and 20 mg FTC per kg once daily, started nine days prior to HIV exposure, and untreated six animals were used as a control group. The FTC dose is comparable to standard human dose, and tenfovir exposure was slightly higher. All animals were exposed rectally with SHIV comparable to viral load levels found in semen during acute HIV infection. Historic data on control macaques using this repeat exposure model shows that 4 virus challenges infect ~ 75% of the animals.

Of 6 controls, 4 (67%) became infected after 4 challenges (median = 2.5; range = 2 to 4). In contrast, all 6 animals treated with TDF/FTC were fully protected. After 10 additional virus challenges, 1 of 2 remaining controls became infected while all 6 TDF/FTC-treated animals remained uninfected.

The experiment was repeated using FTC monotherapy, with up to 10 HIV exposures, with one animal becoming infected at week 5 and another at week 10. Surprisingly, resistance data on the first animal remained wild-type with no M184V after a further 5 weeks monotherapy.

Comment

Studies are clearly required to understand whether a similar level of protection would be provided for adults. In this study the theoretical advantage of dual therapy appeared to result in reduced transmission.