Intermittent tenofovir/FTC PrEP offers monkeys some protection
30 October 2008. Related: Conference reports, HIV prevention and transmission, Intl Transmission Workshop 3rd Mexico 2008.
Mark Mascolini for NATAP.org
Two-dose intermittent pre-exposure prophylaxis (PrEP) with Truvada (tenofovir plus emtricitabine) protected male macaques from rectal exposure to a simian-HIV hybrid virus (SHIV) as well as daily Truvada did in an earlier study by scientists from the US Centers for Disease Control (CDC). [1]
But two-dose PReP did not protect all animals in any of the four 6-monkey groups who got the drugs at different times relative to SHIV exposure.
Trials of daily Truvada PrEP are now under way in different human populations at high risk of HIV infection. An earlier monkey trial of emtricitabine alone and tenofovir/emtricitabine found better protection from SHIV with the two drugs. [2]
In the new study Gerardo Garcia-Lerma and CDC colleagues rectally exposed 24 male Rhesus macaques to SHIV, a simian immunodeficiency virus with an HIV coat, once weekly over 14 weeks. They split the monkeys into four groups of 6, giving human-equivalent doses of Truvada to each group through a mouth-to-stomach tube at different times:
- Group 1: 2 hours before and 22 hours after SHIV exposure
- Group 2: 22 hours before and 2 hours after SHIV exposure
- Group 3: 3 days before and 2 hours after SHIV exposure
- Group 4: 2 hours after and 26 hours after (postexposure prophylaxis, or PEP)
In a comparison group of 24 untreated monkeys, 23 became infected with SHIV (detected in plasma and blood cells) after a median of 2 rectal exposures (range 1 to 12). In contrast 3 of 6 group-1 animals did not pick up SHIV after 14 exposures, 5 of 6 group-2 animals remained free of SHIV after 14 exposures, 5 of 6 group-3 animals remained uninfected after 14 exposures, and (in an ongoing study) 3 of 6 group-4 animals are free of virus after 12 exposures.
Compared with the untreated macaques, group 1 had a 3.7-fold lower risk of SHIV infection (P = 0.04), group 2 had a 15.5-fold lower risk (P = 0.008), and group 3 had a 14.0-fold lower risk (P = 0.01). Risk of SHIV infection in these three groups did not differ significantly from infection risk in monkeys who received daily Truvada PrEP in the earlier trial. In animals that did become infected, viremia was about 10-fold lower than in control animals. Resistant virus did not emerge in animals whose PrEP failed.
Garcia-Lerma and coworkers speculated “the long intracellular drug half-life of tenofovir and emtricitabine may explain the extended window for protection by the pre-exposure dosing and provides opportunities for different intermittent PrEP regimens.”
In a separate study also reported by NATAP, tenofovir/FTC formulated in a stable vaginally applied gel protected 6 of 6 female pigtail macaques from 20 SHIV exposures. [3]
Source: http://www.natap.org
References:
- Garcia-Lerma J, Cong M, Masciotra S, et al. Intermittent pre-exposure prophylaxis (PrEP) with oral Truvada protects macaques against repeated rectal SHIV exposures. 3rd International Workshop on HIV Transmission: Principles of Intervention. 31 July -2 August 2008, Mexico City. Abstract 40.
- Garcia-Lerma JG, Otten RA, Qari SH, et al. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med. 2008;5(2):e28 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225435
- Parikh UM, Sharma S, Cong M, et al. Complete protection against repeated vaginal SHIV exposures in macaques by a combination emtricitabine and tenofovir topical gel. 3rd International Workshop on HIV Transmission: Principles of Intervention. 31 July -2 August 2008, Mexico City. Abstract 41.