Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.
BACKGROUND
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. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.


RESULTS
We used a repeat-exposure macaque model with 14 weekly rectal virus 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.


CONCLUSIONS
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 SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.
García-Lerma
J Gerardo
JG
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. GGarcia-Lerma@cdc.gov
Otten
Ron A
RA
Qari
Shoukat H
SH
Jackson
Eddie
E
Cong
Mian-Er
ME
Masciotra
Silvina
S
Luo
Wei
W
Kim
Caryn
C
Adams
Debra R
DR
Monsour
Michael
M
Lipscomb
Jonathan
J
Johnson
Jeffrey A
JA
Delinsky
David
D
Schinazi
Raymond F
RF
Janssen
Robert
R
Folks
Thomas M
TM
Heneine
Walid
W
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D000818:Animals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D004334:Drug Administration Schedule; D000068679:Emtricitabine; D008251:Macaca; D008253:Macaca mulatta; D063065:Organophosphonates / Q000008:administration & dosage* / Q000097:blood; D012007:Rectum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000517:prevention & control* / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000378:metabolism; D000068698:Tenofovir
D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine