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Current HIV Research


ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Review Article

The Importance of Tissue Sanctuaries and Cellular Reservoirs of HIV-1

Author(s): William Kalada and Theodore James Cory*

Volume 20, Issue 2, 2022

Published on: 21 February, 2022

Page: [102 - 110] Pages: 9

DOI: 10.2174/1570162X20666211227161237

Price: $65


Purpose of Review: There have been significant developments in the treatment of people living with HIV-1/AIDS with current antiretroviral therapies; however, these developments have not been able to achieve a functional or sterilizing cure for HIV-1. While there are multiple barriers, one such barrier is the existence of pharmacological sanctuaries and viral reservoirs where the concentration of antiretrovirals is suboptimal, which includes the gut-associated lymphoid tissue, central nervous system, lymph nodes, and myeloid cells. This review will focus on illustrating the significance of these sanctuaries, specific barriers to optimal antiretroviral concentrations in each of these sites, and potential strategies to overcome these barriers.

Recent Findings: Research and studies have shown that a uniform antiretroviral distribution is not achieved with current therapies. This may allow low-level replication associated with low antiretroviral concentrations in these sanctuaries/reservoirs. Many methods are being investigated to increase antiretroviral concentrations in these sites, such as blocking transporting enzymes functions, modulating transporter expression and nanoformulations of current antiretrovirals. While these methods have been shown to increase antiretroviral concentrations in the sanctuaries/reservoirs, no functional or sterilizing cure has been achieved due to these approaches.

Summary: New methods of increasing antiretroviral concentrations at the specific sites of HIV-1 replication has the potential to target cellular reservoirs. In order to optimize antiretroviral distribution into viral sanctuaries/reservoirs, additional research is needed.

Keywords: HIV-1, sanctuary, reservoir, transporter, nanoformulations, antiretroviral, GALT, RALT, CNS, monocytes.

Graphical Abstract
Eisele E, Siliciano RF. Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity 2012; 37(3): 377-88.
[] [PMID: 22999944]
Sengupta S, Siliciano RF. Targeting the latent reservoir for HIV-1. Immunity 2018; 48(5): 872-95.
[] [PMID: 29768175]
Lorenzo-Redondo R, Fryer HR, Bedford T, et al. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 2016; 530(7588): 51-6.
[] [PMID: 26814962]
Fletcher CV, Staskus K, Wietgrefe SW, et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci USA 2014; 111(6): 2307-12.
[] [PMID: 24469825]
Whyte-Allman SK, Bendayan R. HIV-1 sanctuary sites-the role of membrane-associated drug transporters and drug metabolic enzymes. AAPS J 2020; 22(5): 118.
[] [PMID: 32875457]
Huot N, Bosinger SE, Paiardini M, Reeves RK, Müller-Trutwin M. Lymph node cellular and viral dynamics in natural hosts and impact for HIV cure strategies. front immunol 2018; 9: 780.
[] [PMID: 29725327]
Horiike M, Iwami S, Kodama M, et al. Lymph nodes harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy. Virology 2012; 423(2): 107-18.
[] [PMID: 22196013]
Hong JJ, Chang K-T, Villinger F. The dynamics of T and B cells in lymph node during chronic HIV infection: TFH and HIV, unhappy dance partners? Front Immunol 2016; 7: 522.
[] [PMID: 27920778]
Scholz EMB, Kashuba ADM. The lymph node reservoir: physiology, HIV infection, and antiretroviral therapy. Clin Pharmacol Ther 2021; 109(4): 918-27.
[] [PMID: 33529355]
Whyte-Allman S-K, Hoque MT, Gilmore JC, Kaul R, Routy J-P, Bendayan R. Orchid Study Group. Drug efflux transporters and metabolic enzymes in human circulating and testicular T-cell subsets: relevance to HIV pharmacotherapy. AIDS 2020; 34(10): 1439-49.
[] [PMID: 32310902]
Thompson CG, Gay CL, Kashuba ADM. HIV persistence in gut-associated lymphoid tissues: Pharmacological challenges and opportunities. AIDS Res Hum Retroviruses 2017; 33(6): 513-23.
[] [PMID: 28398774]
Veazey RS, DeMaria M, Chalifoux LV, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 1998; 280(5362): 427-31.
[] [PMID: 9545219]
Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol 2003; 77(21): 11708-17.
[] [PMID: 14557656]
Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev 2013; 26(1): 2-18.
[] [PMID: 23297256]
Berg RD. Bacterial translocation from the gastrointestinal tract. J Med 1992; 23(3-4): 217-44.
[PMID: 1479301]
Misaka S, Müller F, Fromm MF. Clinical relevance of drug efflux pumps in the gut. Curr Opin Pharmacol 2013; 13(6): 847-52.
[] [PMID: 24028838]
Kis O, Robillard K, Chan GN, Bendayan R. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci 2010; 31(1): 22-35.
[] [PMID: 20004485]
Cory TJ, Schacker TW, Stevenson M, Fletcher CV. Overcoming pharmacologic sanctuaries. Curr Opin HIV AIDS 2013; 8(3): 190-5.
[] [PMID: 23454865]
Englund G, Rorsman F, Rönnblom A, et al. Regional levels of drug transporters along the human intestinal tract: co-expression of ABC and SLC transporters and comparison with Caco-2 cells. Eur J Pharm Sci 2006; 29(3-4): 269-77.
[] [PMID: 16822659]
Thompson CG, Rosen EP, Prince HMA, et al. Heterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three species. Sci Transl Med 2019; 11(499): eaap8758.
[] [PMID: 31270274]
De Rosa MF, Robillard KR, Kim CJ, et al. Expression of membrane drug efflux transporters in the sigmoid colon of HIV-infected and uninfected men. J Clin Pharmacol 2013; 53(9): 934-45.
[] [PMID: 23856938]
Rothenberger MK, Keele BF, Wietgrefe SW, et al. Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc Natl Acad Sci USA 2015; 112(10): E1126-34.
[] [PMID: 25713386]
Balcom EF, Roda WC, Cohen EA, Li MY, Power C. HIV-1 persistence in the central nervous system: Viral and host determinants during antiretroviral therapy. Curr Opin Virol 2019; 38: 54-62.
[] [PMID: 31390580]
Osborne O, Peyravian N, Nair M, Daunert S, Toborek M. The paradox of HIV blood-brain barrier penetrance and antiretroviral drug delivery deficiencies. Trends Neurosci 2020; 43(9): 695-708.
[] [PMID: 32682564]
Veenhuis RT, Clements JE, Gama L. HIV eradication strategies: Implications for the central nervous system. Curr HIV/AIDS Rep 2019; 16(1): 96-104.
[] [PMID: 30734905]
Scutari R, Alteri C, Perno CF, Svicher V, Aquaro S. The role of HIV infection in neurologic injury. Brain Sci 2017; 7(4): 38.
[] [PMID: 28383502]
Kramer-Hämmerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R. Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 2005; 111(2): 194-213.
[] [PMID: 15885841]
del Palacio M, Álvarez S, Muñoz-Fernández MÁ. HIV-1 infection and neurocognitive impairment in the current era. Rev Med Virol 2012; 22(1): 33-45.
[] [PMID: 21990255]
Verani A, Gras G, Pancino G. Macrophages and HIV-1: Dangerous liaisons. Mol Immunol 2005; 42(2): 195-212.
[] [PMID: 15488608]
Gatanaga H, Oka S, Ida S, Wakabayashi T, Shioda T, Iwamoto A. Active HIV-1 redistribution and replication in the brain with HIV encephalitis. Arch Virol 1999; 144(1): 29-43.
[] [PMID: 10076507]
Marban C, Forouzanfar F, Ait-Ammar A, et al. Targeting the brain reservoirs: Toward an HIV cure. Front Immunol 2016; 7: 397.
[] [PMID: 27746784]
Ko A, Kang G, Hattler JB, et al. Macrophages but not astrocytes harbor HIV DNA in the brains of HIV-1-infected aviremic individuals on suppressive antiretroviral therapy. J Neuroimmune Pharmacol 2019; 14(1): 110-9.
[] [PMID: 30194646]
Wallet C, De Rovere M, Van Assche J, et al. Microglial cells: The main HIV-1 reservoir in the brain. Front Cell Infect Microbiol 2019; 9: 362.
[] [PMID: 31709195]
Campbell JH, Hearps AC, Martin GE, Williams KC, Crowe SM. The importance of monocytes and macrophages in HIV pathogenesis, treatment, and cure. AIDS 2014; 28(15): 2175-87.
[] [PMID: 25144219]
Smail RC, Brew BJ. HIV-associated neurocognitive disorder. Handb Clin Neurol 2018; 152: 75-97.
[] [PMID: 29604986]
Tan IL, McArthur JC. HIV-associated neurological disorders: A guide to pharmacotherapy. CNS Drugs 2012; 26(2): 123-34.
[] [PMID: 22201342]
Eggers C, Arendt G, Hahn K, et al. German Association of Neuro-AIDS und Neuro-Infectiology (DGNANI). HIV-1-associated neurocognitive disorder: Epidemiology, pathogenesis, diagnosis, and treatment. J Neurol 2017; 264(8): 1715-27.
[] [PMID: 28567537]
Urquhart BL, Kim RB. Blood-brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol 2009; 65(11): 1063-70.
[] [PMID: 19727692]
Letendre S, Marquie-Beck J, Capparelli E, et al. CHARTER Group. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008; 65(1): 65-70.
[] [PMID: 18195140]
Jenabian M-A, Costiniuk CT, Mehraj V, et al. Orchid study group. Immune tolerance properties of the testicular tissue as a viral sanctuary site in ART-treated HIV-infected adults. AIDS 2016; 30(18): 2777-86.
[] [PMID: 27677162]
Shehu-Xhilaga M, Kent S, Batten J, et al. The testis and epididymis are productively infected by SIV and SHIV in juvenile macaques during the post-acute stage of infection. Retrovirology 2007; 4(1): 7.
[] [PMID: 17266752]
Miller RL, Ponte R, Jones BR, et al. ORCHID Study Group. HIV diversity and genetic compartmentalization in blood and testes during suppressive antiretroviral therapy. J Virol 2019; 93(17): e00755-19.
[] [PMID: 31189714]
Mruk DD, Cheng CY. The mammalian blood-testis barrier: Its biology and regulation. Endocr Rev 2015; 36(5): 564-91.
[] [PMID: 26357922]
Miller SR, Cherrington NJ. Transepithelial transport across the blood-testis barrier. Reproduction 2018; 156(6): R187-94.
[] [PMID: 30328342]
Mital P, Hinton BT, Dufour JM. The blood-testis and blood-epididymis barriers are more than just their tight junctions. Biol Reprod 2011; 84(5): 851-8.
[] [PMID: 21209417]
Roulet V, Satie AP, Ruffault A, et al. Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro. Am J Pathol 2006; 169(6): 2094-103.
[] [PMID: 17148672]
Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med 1998; 339(25): 1803-9.
[] [PMID: 9854115]
Le Tortorec A, Dejucq-Rainsford N. HIV infection of the male genital tract--consequences for sexual transmission and reproduction. Int J Androl 2010; 33(1): e98-e108.
[] [PMID: 19531082]
Su L, Mruk DD, Cheng CY. Drug transporters, the blood-testis barrier, and spermatogenesis. J Endocrinol 2011; 208(3): 207-23.
[PMID: 21134990]
Su L, Cheng CY, Mruk DD. Drug transporter, P-glycoprotein (MDR1), is an integrated component of the mammalian blood-testis barrier. Int J Biochem Cell Biol 2009; 41(12): 2578-87.
[] [PMID: 19720156]
Bart J, Hollema H, Groen HJ, et al. The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours. Eur J Cancer 2004; 40(14): 2064-70.
[] [PMID: 15341980]
Ponte R, Dupuy FP, Brimo F, et al. ORCHID study group. Characterization of myeloid cell populations in human testes collected after sex reassignment surgery. J Reprod Immunol 2018; 125: 16-24.
[] [PMID: 29136520]
Pérez CV, Theas MS, Jacobo PV, Jarazo-Dietrich S, Guazzone VA, Lustig L. Dual role of immune cells in the testis: Protective or pathogenic for germ cells? Spermatogenesis 2013; 3(1): e23870.
[] [PMID: 23687616]
Janneh O, Anwar T, Jungbauer C, et al. P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther 2009; 14(7): 965-74.
[] [PMID: 19918100]
Mu Y, Kodidela S, Wang Y, Kumar S, Cory TJ. The dawn of precision medicine in HIV: State of the art of pharmacotherapy. Expert Opin Pharmacother 2018; 19(14): 1581-95.
[] [PMID: 30234392]
Cory TJ, He H, Winchester LC, Kumar S, Fletcher CV. Alterations in P-glycoprotein expression and function between macrophage subsets. Pharm Res 2016; 33(11): 2713-21.
[] [PMID: 27431863]
Murray JM, Zaunders J, Emery S, et al. HIV dynamics linked to memory CD4+ T cell homeostasis. PLoS One 2017; 12(10): e0186101.
[] [PMID: 29049331]
Kwon KJ, Timmons AE, Sengupta S, et al. Different human resting memory CD4+ T cell subsets show similar low inducibility of latent HIV-1 proviruses. Sci Transl Med 2020; 12(528): eaax6795.
[] [PMID: 31996465]
Douek DC, Brenchley JM, Betts MR, et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 2002; 417(6884): 95-8.
[] [PMID: 11986671]
Hsiao F, Frouard J, Gramatica A, et al. Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection. PLoS Pathog 2020; 16(4): e1008450.
[] [PMID: 32353080]
Shan L, Deng K, Gao H, et al. Transcriptional reprogramming during effector-to-memory transition renders CD4+ T cells permissive for latent HIV-1 infection. Infect Immun 2017; 47(4): 766-775.e3.
[] [PMID: 29045905]
Siliciano JD, Kajdas J, Finzi D, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 2003; 9(6): 727-8.
[] [PMID: 12754504]
Pušnik J, Eller MA, Tassaneetrithep B, et al. Expansion of stem cell-like CD4+ memory T cells during acute HIV-1 infection is linked to rapid disease progression. J Virol 2019; 93(14): e00377-19.
[] [PMID: 31043532]
Buzon MJ, Sun H, Li C, et al. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med 2014; 20(2): 139-42.
[] [PMID: 24412925]
Crooks AM, Bateson R, Cope AB, et al. Precise quantitation of the latent HIV-1 reservoir: Implications for eradication strategies. J Infect Dis 2015; 212(9): 1361-5.
[] [PMID: 25877550]
Whitney JB, Hill AL, Sanisetty S, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature 2014; 512(7512): 74-7.
[] [PMID: 25042999]
Bashiri K, Rezaei N, Nasi M, Cossarizza A. The role of latency reversal agents in the cure of HIV: A review of current data. Immunol Lett 2018; 196: 135-9.
[] [PMID: 29427743]
DiNapoli SR, Ortiz AM, Wu F, et al. Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques. JCI Insight 2017; 2(4): e91214.
[] [PMID: 28239657]
Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 1986; 233(4760): 215-9.
[] [PMID: 3014648]
Zalar A, Figueroa MI, Ruibal-Ares B, et al. Macrophage HIV-1 infection in duodenal tissue of patients on long term HAART. Antiviral Res 2010; 87(2): 269-71.
[] [PMID: 20471997]
Cribbs SK, Lennox J, Caliendo AM, Brown LA, Guidot DM. Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AIDS Res Hum Retroviruses 2015; 31(1): 64-70.
[] [PMID: 25134819]
Churchill MJ, Gorry PR, Cowley D, et al. Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J Neurovirol 2006; 12(2): 146-52.
[] [PMID: 16798676]
Yukl SA, Shergill AK, Ho T, et al. The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: Implications for viral persistence. J Infect Dis 2013; 208(8): 1212-20.
[] [PMID: 23852128]
Yukl SA, Sinclair E, Somsouk M, et al. A comparison of methods for measuring rectal HIV levels suggests that HIV DNA resides in cells other than CD4+ T cells, including myeloid cells. AIDS 2014; 28(3): 439-42.
[] [PMID: 24322272]
Honeycutt JB, Wahl A, Baker C, et al. Macrophages sustain HIV replication in vivo independently of T cells. J Clin Invest 2016; 126(4): 1353-66.
[] [PMID: 26950420]
Honeycutt JB, Thayer WO, Baker CE, et al. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat Med 2017; 23(5): 638-43.
[] [PMID: 28414330]
Koppensteiner H, Brack-Werner R, Schindler M. Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology 2012; 9(1): 82.
[] [PMID: 23035819]
Soulet D, Rivest S. Bone-marrow-derived microglia: Myth or reality? Curr Opin Pharmacol 2008; 8(4): 508-18.
[] [PMID: 18487084]
Pulliam L, Gascon R, Stubblebine M, McGuire D, McGrath MS. Unique monocyte subset in patients with AIDS dementia. Lancet 1997; 349(9053): 692-5.
[] [PMID: 9078201]
Gavegnano C, Detorio MA, Bassit L, Hurwitz SJ, North TW, Schinazi RF. Cellular pharmacology and potency of HIV-1 nucleoside analogs in primary human macrophages. Antimicrob Agents Chemother 2013; 57(3): 1262-9.
[] [PMID: 23263005]
Gavegnano C, Kennedy EM, Kim B, Schinazi RF. The impact of macrophage nucleotide pools on HIV-1 reverse transcription, viral replication, and the development of novel antiviral agents. Mol Biol Int 2012; 2012: 625983.
[] [PMID: 22811909]
Mu Y, Patters BJ, Midde NM, He H, Kumar S, Cory TJ. Tobacco and antiretrovirals modulate transporter, metabolic enzyme, and antioxidant enzyme expression and function in polarized macrophages. Curr HIV Res 2018; 16(5): 354-63.
[] [PMID: 30706821]
He H, Buckley M, Britton B, et al. Polarized macrophage subsets differentially express the drug efflux transporters MRP1 and BCRP, resulting in altered HIV production. Antivir Chem Chemother 2018; 26: 2040206617745168.
[] [PMID: 29343083]
Jorajuria S, Dereuddre-Bosquet N, Becher F, et al. ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages. Antivir Ther 2004; 9(4): 519-28.
[PMID: 15456083]
Seral C, Carryn S, Tulkens PM, Van Bambeke F. Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus. J Antimicrob Chemother 2003; 51(5): 1167-73.
[] [PMID: 12697643]
Mantovani A, Locati M. Orchestration of macrophage polarization. Blood 2009; 114(15): 3135-6.
[] [PMID: 19815678]
Alfano M, Graziano F, Genovese L, Poli G. Macrophage polarization at the crossroad between HIV-1 infection and cancer development. Arterioscler Thromb Vasc Biol 2013; 33(6): 1145-52.
[] [PMID: 23677880]
Chihara T, Hashimoto M, Osman A, et al. HIV-1 proteins preferentially activate anti-inflammatory M2-type macrophages. J Immunol 2012; 188(8): 3620-7.
[] [PMID: 22407921]
Herbein G, Gras G, Khan KA, Abbas W. Macrophage signaling in HIV-1 infection. Retrovirology 2010; 7(1): 34.
[] [PMID: 20380698]
Cassol E, Cassetta L, Alfano M, Poli G. Macrophage polarization and HIV-1 infection. J Leukoc Biol 2010; 87(4): 599-608.
[] [PMID: 20042468]
Gong Y, Rao PSS, Sinha N, Ranjit S, Cory TJ, Kumar S. The role of cytochrome P450 2E1 on ethanol-mediated oxidative stress and HIV replication in human monocyte-derived macrophages. Biochem Biophys Rep 2018; 17: 65-70.
[] [PMID: 30582009]
Hutson JL, Wickramasinghe SN. Expression of CYP2E1 by human monocyte-derived macrophages. J Pathol 1999; 188(2): 197-200.
[<197::AID-PATH295>3.0.CO;2-M] [PMID: 10398164]
Kumar S. Role of cytochrome P450 systems in substance of abuse mediated HIV-1 pathogenesis and neuro AIDS. J Drug Metab Toxicol 2012; 03: 01.
Alam C, Whyte-Allman S-K, Omeragic A, Bendayan R. Role and modulation of drug transporters in HIV-1 therapy. Adv Drug Deliv Rev 2016; 103: 121-43.
[] [PMID: 27181050]
Huls M, Russel FG, Masereeuw R. The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther 2009; 328(1): 3-9.
[] [PMID: 18791064]
Marquez B, Van Bambeke F. ABC multidrug transporters: Target for modulation of drug pharmacokinetics and drug-drug interactions. Curr Drug Targets 2011; 12(5): 600-20.
[] [PMID: 21039335]
Robillard KR, Chan GNY, Zhang G, la Porte C, Cameron W, Bendayan R. Role of P-glycoprotein in the distribution of the HIV protease inhibitor atazanavir in the brain and male genital tract. Antimicrob Agents Chemother 2014; 58(3): 1713-22.
[] [PMID: 24379203]
Robillard KR, Hoque T, Bendayan R. Expression of ATP-binding cassette membrane transporters in rodent and human sertoli cells: Relevance to the permeability of antiretroviral therapy at the blood-testis barrier. J Pharmacol Exp Ther 2012; 340(1): 96-108.
[] [PMID: 21990609]
Kis O, Zastre JA, Hoque MT, Walmsley SL, Bendayan R. Role of drug efflux and uptake transporters in atazanavir intestinal permeability and drug-drug interactions. Pharm Res 2013; 30(4): 1050-64.
[] [PMID: 23224979]
Mukhopadhya I, Murray GI, Berry S, et al. Drug transporter gene expression in human colorectal tissue and cell lines: Modulation with antiretrovirals for microbicide optimization. J Antimicrob Chemother 2016; 71(2): 372-86.
[] [PMID: 26514157]
Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet 2017; 390(10101): 1499-510.
[] [PMID: 28750935]
Zhou T, Su H, Dash P, et al. Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials 2018; 151: 53-65.
[] [PMID: 29059541]
Sillman B, Bade AN, Dash PK, et al. Creation of a long-acting nanoformulated dolutegravir. Nat Commun 2018; 9(1): 443.
[] [PMID: 29402886]
Gong Y, Chowdhury P, Nagesh PKB, et al. Nanotechnology approaches for delivery of cytochrome P450 substrates in HIV treatment. Expert Opin Drug Deliv 2019; 16(8): 869-82.
[] [PMID: 31328582]
Gong Y, Zhi K, Nagesh PKB, et al. An elvitegravir nanoformulation crosses the blood-brain barrier and suppresses HIV-1 replication in microglia. Viruses 2020; 12(5): 564.
[] [PMID: 32443728]
Gong Y, Chowdhury P, Nagesh PKB, et al. Novel elvitegravir nanoformulation for drug delivery across the blood-brain barrier to achieve HIV-1 suppression in the CNS macrophages. Sci Rep 2020; 10(1): 3835.
[] [PMID: 32123217]
Dash PK, Kaminski R, Bella R, et al. Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice. Nat Commun 2019; 10(1): 2753.
[] [PMID: 31266936]
Dash PK, Kevadiya BD, Su H, Banoub MG, Gendelman HE. Pathways towards human immunodeficiency virus elimination. EBioMedicine 2020; 53: 102667.
[] [PMID: 32114397]

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