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Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir
- Source :
- PLoS Medicine, Vol 5, Iss 2, p e28 (2008), PLoS Medicine
- Publication Year :
- 2008
- Publisher :
- Public Library of Science (PLoS), 2008.
-
Abstract
- 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.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.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.
- Subjects :
- Pediatrics
medicine.medical_specialty
Organophosphonates
Simian Acquired Immunodeficiency Syndrome
lcsh:Medicine
Viremia
medicine.disease_cause
Emtricitabine
Macaque
Deoxycytidine
Drug Administration Schedule
03 medical and health sciences
Pre-exposure prophylaxis
0302 clinical medicine
Pharmacotherapy
biology.animal
Virology
medicine
HIV Infection/AIDS
Animals
030212 general & internal medicine
Tenofovir
030304 developmental biology
Sexually transmitted diseases
0303 health sciences
biology
Transmission (medicine)
business.industry
Adenine
lcsh:R
Rectum
General Medicine
Simian immunodeficiency virus
medicine.disease
Macaca mulatta
3. Good health
Clinical research
Infectious Diseases
Macaca
Women's Health
Simian Immunodeficiency Virus
Sexual Health
business
medicine.drug
Perspectives
Subjects
Details
- Language :
- English
- ISSN :
- 15491676 and 15491277
- Volume :
- 5
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS Medicine
- Accession number :
- edsair.doi.dedup.....444c3f63a9c769f1df92aec638745262