title: A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy.
abstract: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) and rilpivirine (RVP) (2ART), a second received LA CAB, lamivudine, abacavir and RVP (4ART), a third were left untreated and a fourth served as an uninfected control. After 4 weeks of LA ART treatment, blood, spleen and bone marrow (BM) cells were collected then phenotypically characterized. CD4+ T cell subsets, macrophages and hematopoietic progenitor cells were analyzed for HIV-1 nucleic acids by droplet digital PCR.
  
  
  
  Plasma viral loads were reduced by two log10or to undetectable levels in the 2 and 4ART regimens, respectively. Numbers and distributions of CD4+ memory and regulatory T cells, macrophages and hematopoietic progenitor cells were significantly altered by HIV-1 infection and by both ART regimens. ART reduced viral DNA and RNA in all cell and tissue compartments. While memory cells were the dominant T cell reservoir, integrated HIV-1 DNA was also detected in the BM and spleen macrophages in both regimen-treated mice.
  
  
  
  Despite vigorous ART regimens, HIV-1 DNA and RNA were easily detected in mature macrophages supporting their potential role as an infectious viral reservoir.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Mariluz
authors.initials: M
authors.lastname: Araínga
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Benson
authors.initials: B
authors.lastname: Edagwa
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Larisa Y
authors.initials: LY
authors.lastname: Poluektova
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA. hegendel@unmc.edu.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004197:Disease Reservoirs; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000821:virology*; D016513:Mice, SCID; D010949:Plasma / Q000821:virology; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D016896:Treatment Outcome; D019562:Viral Load; D017735:Virus Latency
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral
keywords: Antiretroviral therapy; HIV-1; Humanized mice; Monocyte–macrophage; T effector cells; Viral reservoirs