HIV and Hepatitis.com Coverage of the
14th Annual Conference on Retroviruses
and Opportunistic Infections (14th CROI)
February 25 - 28, 2007, Los Angeles, CA
Pre-exposure Prophylaxis with Emtricitabine Plus Tenofovir Protects Monkeys against SHIV Infection

By Liz Highleyman

In recent years, pre-exposure prophylaxis (PrEP) using antiretroviral therapy has been studied as a method of preventing HIV infection. PrEP refers to taking antiretroviral drugs before exposure, and should not be confused with post-exposure prophylaxis (PEP), which refers to therapy taken after exposure in an attempt to prevent HIV from taking hold in the body.

Past animal studies have shown that oral or injected tenofovir (Viread), especially when used with emtricitabine (Emtriva) -- the 2 drugs that make up the Truvada combination pill -- reduced the risk of infection in macaque monkeys exposed to a virus related to HIV.

In the latest study, presented in a poster at the 14th Conference on Retroviruses and Opportunistic Infections last month in Los Angeles, researchers with the Centers for Disease Control and Prevention (CDC) treated 18 macaques with one of 3 regimens:

• Subcutaneously injected emtricitabine (20 mg/kg);

• Injected emtricitabine plus tenofovir (20 and 22 mg/kg);

• Oral emtricitabine plus tenofovir (20 and 22 mg/kg).

The investigators noted that although the tenofovir doses were the same, injection of tenofovir provides higher plasma concentrations compared with oral administration. The monkeys were then rectally exposed to a chimeric simian/human immunodeficiency virus (SHIV) once weekly for 14 weeks.

Results

• 17 of 18 monkeys that did not receive any PrEP became infected, after a median of 2 SHIV challenges.

• 4 of 6 animals that received injected emtricitabine alone became infected.

• 2 of 6 six monkeys that received oral tenofovir plus emtricitabine were infected, after 9 and 12 SHIV exposures.

• None of the 6 monkeys that received injected tenofovir plus emtricitabine were infected after 14 weekly challenges.

Conclusion

"Data demonstrate that full protection is possible and show a correlation between the level of protection and antiretroviral potency," the researchers concluded. "The model suggests that chemoprophylaxis with potent drug combinations may be more effective than single drugs in preventing sexual HIV transmission in humans."

In a related poster presentation, the same research team reported that the 6 monkeys that became infected despite PrEP had lower SHIV viral load levels than untreated animals. In untreated monkeys, the median peak viral load was 8,000,000 copies/mL, declining to 80,000 within 8 weeks after infection. In the treated animals, viral load peaked at 80,000 copies/mL and declined to 300 by week 8. Breakthrough infections were with wild-type virus. Two infected monkeys subsequently developed the M184V mutation, associated with emtricitabine resistance; none developed the K65R tenofovir-resistance mutation.

These results suggest that even if PrEP does not prevent HIV infection, it may delay disease progression, working like a therapeutic vaccine. However, the potential for emergence of drug resistance remains a concern.

03/13/07

References

J Garcia-Lerma, R Otten, S Qari, and others. Higher Antiretroviral Drug Potency Correlates with Increased Protection against Rectal SHIV Transmission. 14th Conference on Retroviruses and Opportunistic Infections (CROI). Los Angeles, February 25-28, 2007. Abstract 986 (poster).

J G Garcia-Lerma, R Otten, S Masciotra, and others. Blunted Viremia in Macaques Failing Chemoprophylaxis with FTC or FTC/TDF Combination. 14th CROI. Abstract 985 (poster).













































14th croi