Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-02-01
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| Series: | PLoS Medicine |
| Online Access: | http://europepmc.org/articles/PMC2225435?pdf=render |
| _version_ | 1830382136498061312 |
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| author | J Gerardo García-Lerma Ron A Otten Shoukat H Qari Eddie Jackson Mian-Er Cong Silvina Masciotra Wei Luo Caryn Kim Debra R Adams Michael Monsour Jonathan Lipscomb Jeffrey A Johnson David Delinsky Raymond F Schinazi Robert Janssen Thomas M Folks Walid Heneine |
| author_facet | J Gerardo García-Lerma Ron A Otten Shoukat H Qari Eddie Jackson Mian-Er Cong Silvina Masciotra Wei Luo Caryn Kim Debra R Adams Michael Monsour Jonathan Lipscomb Jeffrey A Johnson David Delinsky Raymond F Schinazi Robert Janssen Thomas M Folks Walid Heneine |
| author_sort | J Gerardo García-Lerma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T10:01:04Z |
| format | Article |
| id | doaj.art-200116450461413e9f478877b491dbf5 |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-20T10:01:04Z |
| publishDate | 2008-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-200116450461413e9f478877b491dbf52022-12-21T19:44:20ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762008-02-0152e2810.1371/journal.pmed.0050028Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.J Gerardo García-LermaRon A OttenShoukat H QariEddie JacksonMian-Er CongSilvina MasciotraWei LuoCaryn KimDebra R AdamsMichael MonsourJonathan LipscombJeffrey A JohnsonDavid DelinskyRaymond F SchinaziRobert JanssenThomas M FolksWalid HeneineIn 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.http://europepmc.org/articles/PMC2225435?pdf=render |
| spellingShingle | J Gerardo García-Lerma Ron A Otten Shoukat H Qari Eddie Jackson Mian-Er Cong Silvina Masciotra Wei Luo Caryn Kim Debra R Adams Michael Monsour Jonathan Lipscomb Jeffrey A Johnson David Delinsky Raymond F Schinazi Robert Janssen Thomas M Folks Walid Heneine Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Medicine |
| title | Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. |
| title_full | Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. |
| title_fullStr | Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. |
| title_full_unstemmed | Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. |
| title_short | Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. |
| title_sort | prevention of rectal shiv transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir |
| url | http://europepmc.org/articles/PMC2225435?pdf=render |
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