Characterizing Drug Resistant Virus in SIV-Infected Rhesus Macaques Treated with ART
Publication Date
July 2019
Location
LSU Health Medical Education Building
Document Type
Abstract
Start Date
26-7-2019 9:00 AM
End Date
26-7-2019 12:00 PM
Description
The Simian Immunodeficiency Virus (SIV) infected rhesus macaque exposed to chronic binge alcohol (CBA) has proven to be a highly useful model for elucidating the effects of alcohol misuse on Human Immunodeficiency Virus (HIV) disease. The use of antiretroviral therapy (ART) has significantly reduced the morbidity and mortality from HIV infections and now triple drug therapy is commonly used for treatment of people chronically infected with HIV. Characterizing and understanding drug resistance (DR) to ART in the SIV-infected CBA macaque is important for the refinement of our model. The objective of this study was to characterize the efficacy and development of DR in ART-treated macaques. In our studies, rhesus macaques were given daily infusions via gastric catheter of ethanol or saline for three months prior to SIV-infection. Ten weeks post SIV infection, animals were treated with ART for the duration of the study. Viral loads were measured in plasma weekly. In our well-studied model design, 21 female and 22 male animals received a two ART regimen consisting of reverse transcriptase inhibitors and also received a typical macaque diet which is fairly lean. In a pilot study, 5 female animals received a three drug regimen that consists of two reverse transcriptase inhibitors and an integrase inhibitor, to better represent the clinical treatment currently prescribed for HIV. In this pilot study, animals also received a high fat diet, or a “western” diet, again to better represent our clinical HIV population. To evaluate DR, virus was purified from plasma, pol gene regions were then amplified by RT-PCR, cloned, sequenced and compared to DR database. In the classical model study, viral loads decreased with the initiation of ART. However, this decrease did not reach undetectable levels in all of the animals, which is the ultimate goal of using ART. DR mutations were found in animals with detectable plasma virus. These mutations mapped to those observed in HIV. In the pilot study model, initial viral loads were higher than in the previous study animals, which may be due to their high fat diet. With initiation of the new ART regimen, viral loads have dropped lower in some animals, but the alcohol animals had a poorer response to ART. Viral isolates from these five animals are being analyzed to determine if DR is a factor contributing to persistent viremia. As the DR is thoroughly evaluated in this pilot study, it will provide valuable insight for developing a clinically-relevant model of HIV disease and alcohol misuse.
Recommended Citation
Freeman, Emma R., "Characterizing Drug Resistant Virus in SIV-Infected Rhesus Macaques Treated with ART" (2019). Summer Research Internship Program. 10.
https://digitalscholar.lsuhsc.edu/srip/2019/undergrad/10
Characterizing Drug Resistant Virus in SIV-Infected Rhesus Macaques Treated with ART
LSU Health Medical Education Building
The Simian Immunodeficiency Virus (SIV) infected rhesus macaque exposed to chronic binge alcohol (CBA) has proven to be a highly useful model for elucidating the effects of alcohol misuse on Human Immunodeficiency Virus (HIV) disease. The use of antiretroviral therapy (ART) has significantly reduced the morbidity and mortality from HIV infections and now triple drug therapy is commonly used for treatment of people chronically infected with HIV. Characterizing and understanding drug resistance (DR) to ART in the SIV-infected CBA macaque is important for the refinement of our model. The objective of this study was to characterize the efficacy and development of DR in ART-treated macaques. In our studies, rhesus macaques were given daily infusions via gastric catheter of ethanol or saline for three months prior to SIV-infection. Ten weeks post SIV infection, animals were treated with ART for the duration of the study. Viral loads were measured in plasma weekly. In our well-studied model design, 21 female and 22 male animals received a two ART regimen consisting of reverse transcriptase inhibitors and also received a typical macaque diet which is fairly lean. In a pilot study, 5 female animals received a three drug regimen that consists of two reverse transcriptase inhibitors and an integrase inhibitor, to better represent the clinical treatment currently prescribed for HIV. In this pilot study, animals also received a high fat diet, or a “western” diet, again to better represent our clinical HIV population. To evaluate DR, virus was purified from plasma, pol gene regions were then amplified by RT-PCR, cloned, sequenced and compared to DR database. In the classical model study, viral loads decreased with the initiation of ART. However, this decrease did not reach undetectable levels in all of the animals, which is the ultimate goal of using ART. DR mutations were found in animals with detectable plasma virus. These mutations mapped to those observed in HIV. In the pilot study model, initial viral loads were higher than in the previous study animals, which may be due to their high fat diet. With initiation of the new ART regimen, viral loads have dropped lower in some animals, but the alcohol animals had a poorer response to ART. Viral isolates from these five animals are being analyzed to determine if DR is a factor contributing to persistent viremia. As the DR is thoroughly evaluated in this pilot study, it will provide valuable insight for developing a clinically-relevant model of HIV disease and alcohol misuse.
Comments
Mentor: Angela Amedee, Phd