HIV This Week

Jump to Comments

García-Lerma JG, Otten RA, Qari SH, Jackson E, Cong ME, Masciotra S, Luo W, Kim C, Adams DR, Monsour M, Lipscomb J, Johnson JA, Delinsky D, Schinazi RF, Janssen R, Folks TM, Heneine W. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med. 2008; 5(2):e28.

In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. García-Lerma and colleagues evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. The authors used a repeat-exposure macaque model with 14 weekly rectal simian HIV challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this simian HIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

Editors’ note: None of the macaques receiving a combination of emtricitabine (FTC) and high dose tenofovir (TDF) either daily or only around the time of exposure to a weekly rectal challenge with SIV became infected. The six macaques that did become infected in the other two active (drug-exposed) arms had a lower viral set point suggesting that the risk of onward transmission during primary infection could be less. These are promising findings in an animal model, however drug resistance in two animals suggest that transmission of resistant virus would be a concern. Furthermore, whether people would be willing to inject themselves subcutaneously either on a daily basis or before a likely exposure remains to be seen. There are six trials in the field now using oral TDF or TDF/FTC with results of the first trial expected in 2008.