scholarly journals Short Communication: Comparative Evaluation of Coformulated Injectable Combination Antiretroviral Therapy Regimens in Simian Immunodeficiency Virus-Infected Rhesus Macaques

2016 ◽  
Vol 32 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Gregory Q. Del Prete ◽  
Jeremy Smedley ◽  
Rhonda Macallister ◽  
Gregg S. Jones ◽  
Bei Li ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Comparative Evaluation ◽  
Short Communication ◽  
Rhesus Macaques ◽  
Combination Antiretroviral Therapy ◽  
Immunodeficiency Virus

scholarly journals Evaluating the Intactness of Persistent Viral Genomes in Simian Immunodeficiency Virus-Infected Rhesus Macaques after Initiating Antiretroviral Therapy within One Year of Infection

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Samuel Long ◽  
Christine M. Fennessey ◽  
Laura Newman ◽  
Carolyn Reid ◽  
Sean P. O’Brien ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Genome Sequencing ◽  
Real Time Pcr ◽  
Rhesus Macaques ◽  
Viral Reservoir ◽  
Combination Antiretroviral Therapy ◽  
Viral Dna ◽  
Immunodeficiency Virus

ABSTRACT The major obstacle to more-definitive treatment for HIV infection is the early establishment of virus that persists despite long-term combination antiretroviral therapy (cART) and can cause recrudescent viremia if cART is interrupted. Previous studies of HIV DNA that persists despite cART indicated that only a small fraction of persistent viral sequences was intact. Experimental simian immunodeficiency virus (SIV) infections of nonhuman primates (NHPs) are essential models for testing interventions designed to reduce the viral reservoir. We studied the viral genomic integrity of virus that persists during cART under conditions typical of many NHP reservoir studies, specifically with cART started within 1 year postinfection and continued for at least 9 months. The fraction of persistent DNA in SIV-infected NHPs starting cART during acute or chronic infection was assessed with a multiamplicon, real-time PCR assay designed to analyze locations that are regularly spaced across the viral genome to maximize coverage (collectively referred to as “tile assay”) combined with near-full-length (nFL) single-genome sequencing. The tile assay is used to rapidly screen for major deletions, with nFL sequence analysis used to identify additional potentially inactivating mutations. Peripheral blood mononuclear cells (PBMC) from animals started on cART within 1 month of infection, sampled at least 9 months after cART initiation, contained at least 80% intact genomes, whereas those from animals started on cART 1 year postinfection and treated for 1 year contained intact genomes only 47% of the time. The most common defect identified was large deletions, with the remaining defects caused by APOBEC-mediated mutations, frameshift mutations, and inactivating point mutations. Overall, this approach can be used to assess the intactness of persistent viral DNA in NHPs. IMPORTANCE Molecularly defining the viral reservoir that persists despite antiretroviral therapy and that can lead to rebound viremia if antiviral therapy is removed is critical for testing interventions aimed at reducing this reservoir. In HIV infection in humans with delayed treatment initiation and extended treatment duration, persistent viral DNA has been shown to be dominated by nonfunctional genomes. Using multiple real-time PCR assays across the genome combined with near-full-genome sequencing, we defined SIV genetic integrity after 9 to 18 months of combination antiretroviral therapy in rhesus macaques starting therapy within 1 year of infection. In the animals starting therapy within a month of infection, the vast majority of persistent DNA was intact and presumptively functional. Starting therapy within 1 year increased the nonintact fraction of persistent viral DNA. The approach described here allows rapid screening of viral intactness and is a valuable tool for assessing the efficacy of novel reservoir-reducing interventions.

scholarly journals Emergence of resistance mutations in simian immunodeficiency virus (SIV)-infected rhesus macaques receiving non-suppressive antiretroviral therapy (ART)

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0190908 ◽  
Author(s):  
Benjamin Bruno Policicchio ◽  
Paola Sette ◽  
Cuiling Xu ◽  
George Haret-Richter ◽  
Tammy Dunsmore ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Emergence Of Resistance

scholarly journals Simian Immunodeficiency Virus (SIV) Persistence in Antiretroviral Therapy (ART)-Treated Infant Rhesus Macaques

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Maud Mavigner ◽  
Claire Deleage ◽  
Jakob Habib ◽  
Elias Rosen ◽  
Angela Kashuba ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Immunodeficiency Virus ◽  
Infant Rhesus
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