Skip to main content
SpringerLink
Log in

HIV Compartments and Viral Rebound During Treatment Interruption

  • Living reference work entry
  • First Online:
Encyclopedia of AIDS

  • 183 Accesses

Definition

One of the main challenging characteristics of HIV is its extensive genetic diversity. This diversity is apparent across geography as represented by differing clades, but on a smaller scale exists within an individual. Viral phylogenetic studies within the same individual have shown diversity and divergence of the HIV virus in the multiple cell types and tissues analyzed. These subpopulations are known as viral quasispecies (Blackard 2012). The local environment present in the tissues influences the evolution of the quasispecies and subsequently impacts cellular tropism (i.e., higher affinity to macrophages from brain-derived virus), affects the response to antiretroviral therapy (ART), and ultimately, could affect eradication strategies.

A compartment has been defined as an anatomical site in which the virus is present, and there is limited exchange of viral genetic information with other sites and may contain compartment-specific viral sequences (Eisele and Siliciano 2012)...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Ait-Khaled M, McLaughlin JE, Johnson MA, Emery VC. Distinct HIV-1 long terminal repeat quasispecies present in nervous tissues compared to that in lung, blood and lymphoid tissues of an AIDS patient. AIDS (London, England). 1995;9:675–83.

    Article  CAS  Google Scholar 

  • Barnabas R, Celum C. Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: new insights and interventions. Curr HIV Res. 2012;10(3):228–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blackard J. HIV compartmentalization: a review on a clinically important phenomenon. Curr HIV Res. 2012;10(1):133–42.

    Article  CAS  PubMed  Google Scholar 

  • Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557–93.

    Article  CAS  PubMed  Google Scholar 

  • Buzón MJ, Massanella M, Llibre JM, Esteve A, Dahl V, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010;16(4):460–5.

    Article  PubMed  Google Scholar 

  • Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010;50:773–8.

    Article  PubMed  Google Scholar 

  • Caniglia EC, Cain LE, Justice A, Tate J, Logan R, et al. Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions. Neurology. 2014;83(2):134–41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15(8):893–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chun TW, Nickle DC, Justement JS, Meyers JH, Roby G, et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis. 2008;197:714–20.

    Article  CAS  PubMed  Google Scholar 

  • Churchill M, Nath A. Where does HIV hide? A focus on the central nervous system. Curr Opin HIV AIDS. 2013;8:165–9.

    Article  CAS  PubMed  Google Scholar 

  • Coffin J, Swanstrom R. HIV pathogenesis: dynamics and genetics of viral populations and infected cells. Cold Spring Harb Perspect Med. 2013;3:a012526.

    Article  PubMed  PubMed Central  Google Scholar 

  • Craigo JK, Gupta P. HIV-1 in genital compartments: vexing viral reservoirs. Curr Opin HIV AIDS. 2006;1:97–102.

    PubMed  Google Scholar 

  • Cribbs SK, Lennox J, Caliendo A, Brown LA, Guidot DM. Healthy HIV-1-infected individuals on HAART harbor HIV-1 in their alveolar macrophages. AIDS Res Hum Retroviruses. 2015;31(1):64–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dahl V, Gisslen M, Hagberg L, Peterson J, Shao W, et al. An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy. J Infect Dis. 2014;209:1618–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Davey RT, Bhat N, Yoder C, Chun TW, Metcalf JA, et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A. 1999;96(26):15109–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, et al. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci U S A. 2006;103(41):15160–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisele E, Siliciano RF. Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity. 2012;37(3):377–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eriksson S, Graf EH, Dahl V, Strain MC, Yukl SA, et al. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 2013;9(2):e1003174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999;5(5):512–7.

    Article  CAS  PubMed  Google Scholar 

  • Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A. 2014;111(6):2307–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, et al. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med. 2010;7(8):e1000321.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gianella S, Smith DM, Vargas MV, Little SJ, Richman DD, et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1-infected men who have sex with men. Clin Infect Dis. 2013;57(3):441–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Golden MP, Kim S, Hammer SM, Ladd EA, Schaffer PA, et al. Activation of human immunodeficiency virus by herpes simplex virus. J Infect Dis. 1992;166(3):494–9.

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Perez MP, O’Connell O, Lin R, Sullivan WM, Bell J, et al. Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue. Retrovirology. 2012;9:20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haase AT. Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annu Rev Immunol. 1999;17:625–56.

    Article  CAS  PubMed  Google Scholar 

  • Hamlyn E, Ewings FM, Porter K, Cooper DA, Tambussi G, et al. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One. 2012;7(8):e43754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hatano H, Strain MC, Scherzer R, Bacchetti R, Wentworth D, et al. Increase in 2 – Long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized. Placebo Controlled Trial J Infect Dis. 2013;208:1436–42.

    CAS  PubMed  Google Scholar 

  • Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell. 2013;155(3):540–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hocqueloux L, Prazuck T, Avettand-Fenoel V, Lafeuillade A, Cardon B, et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS (London, England). 2010;24(10):1598–601.

    Article  Google Scholar 

  • Horiike M, Iwami S, Kodama M, Sato A, Watanabe Y, 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.

    Article  CAS  PubMed  Google Scholar 

  • Joos B, Fischer M, Kuster H, Pillai S, Wong JK, et al. HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci USA. 2008;105(43):16725–16730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kearney MF, Spindler J, Shao W, Yu S, Anderson EM, et al. Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy. PLoS Pathog. 2014;10(3):e1004010.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kearney MF, Wiegand A, Shao W, Coffin JM, Mellors JW, et al. Origin of rebound plasma HIV includes cells with identical proviruses that are transcriptionally active before stopping antiretroviral therapy. J Virol. 2015;90(3):1369–76.

    Google Scholar 

  • Kemal KS, Foley B, Burger H, Anastos K, Minkoff H, et al. HIV-1 in genital tract and plasma of women: compartmentalization of viral sequences, coreceptor usage, and glycosylation. Proc Natl Acad Sci U S A. 2003;100:12972–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008;65(1):65–70.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the laboratory to effective clinical trials? AIDS (London, England). 2011;25:885–97.

    Article  Google Scholar 

  • Li JZ, Etemad B, Ahmed H, Aga E, Bosch RJ, et al. The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. AIDS (London, England). 2016;30(3):343–53.

    Google Scholar 

  • Maggiolo F, Callegaro A, Cologni G, Bernardini C, Velenti D, et al. Ultrasensitive assessment of residual low-level HIV viremia in HAART-treated patients and risk of virological failure. J Acquir Immune Defic Syndr. 2012;60(5):474–82.

    Article  Google Scholar 

  • Maldarelli F, Wu X, Su L, Simonetti FR, Shao W, et al. HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science. 2014;345(6193):179–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marconi V, Bonhoeffer S, Paredes R, Lu J, Hoh R, et al. Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. J Acquir Immune Defic Syndr. 2008;48(5):572–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masson L, Mlisana K, Little F, Werner L, Mkhize NN, et al. Defining genital tract cytokine signatures of sexually transmitted infection and bacterial vaginosis in women at high risk of HIV infection: a cross-sectional study. Sex Transm Infect. 2014;90:580–7.

    Article  PubMed  Google Scholar 

  • Masson L, Passmore JS, Liebenberg LJ, Werner L, Baxter C, et al. Genital inflammation and the risk of HIV acquisition in women. Clin Infect Dis. 2015;61(2):260–9.

    Article  PubMed  Google Scholar 

  • Nickle DC, Shriner D, Mittler JE, Frenkel LM, Mullins JI. Importance and detection of virus reservoirs and compartments of HIV infection. Curr Opin Microbiol. 2003;6(4):410–6.

    Article  PubMed  Google Scholar 

  • Olivieri KC, Agopian KA, Mukerji J, Gabuzda D. Evidence of adaptive evolution at the divergence between lymphoid and brain HIV-1 nef genes. AIDS Res Hum Retroviruses. 2010;26(4):495–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pantaleo G, Graziosi C, Butini L, Pizzo PA, Schnittman SM, et al. Lymphoid organs function as major reservoirs for human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991;88(21):9838–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasternak AO, Lukashov VV, Berkhout B. Cell-associated HIV RNA: a dynamic biomarker of viral persistence. Retrovirology. 2013;10:41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997;387:188–91.

    Article  CAS  PubMed  Google Scholar 

  • Pinkevych M, Cromer D, Tolstrup M, Grimm AJ, Cooper DA, et al. HIV reactivation from latency after treatment interruption occurs on average every 5–8 days – implications for HIV remission. PLoS Pathog. 2015;11(7):e1005000.

    Article  PubMed  PubMed Central  Google Scholar 

  • Politch JA, Mayer KH, Welles SL, O’Brien WX, Xu C, et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS. 2012;26(12):1535–43.

    Article  PubMed  PubMed Central  Google Scholar 

  • Power C, McArthur JC, Nath A, Wehrly K, Mayne M, et al. Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients. J Virol. 1998;72(11):9045–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rodger AJ, Lodwick R, Schechter M, Deeks S, Amin J, et al. Mortality in well-controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS (London, England). 2013;27:973–9.

    Article  CAS  Google Scholar 

  • Rong L, Perelson AS. Modeling HIV persistence, the latent reservoir, and viral blips. J Theor Biol. 2009;260(2):308–31.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rothenberger MK, Keele BF, Wietgrefe SW, Fletcher CV, Beilman GJ, 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.

    Google Scholar 

  • Rouzioux C, Richman D. How to best measure HIV reservoirs? Curr Opin HIV AIDS. 2013;8(3):170–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sáez-Cirión A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, et al. Post-treatment HIV controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PLoS Pathog. 2013;9(3):e1003211.

    Article  PubMed  PubMed Central  Google Scholar 

  • Santoro MM, Fabeni L, Armenia D, Alteri C, Pinto DD, et al. Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels. Clin Infect Dis. 2014;58(8):1156–64.

    Article  CAS  PubMed  Google Scholar 

  • Shan L, Rabi SA, Laird GM, Eisele EE, Zhang H, et al. A novel PCR assay for quantification of HIV-1 RNA. J Virol. 2013;87(11):6521–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, 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.

    Article  CAS  PubMed  Google Scholar 

  • Sonza S, Mutimer HP, Oelrichs R, Jardine D, Harvey H, et al. Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy. AIDS (London, England). 2001;15:17–22.

    Article  CAS  Google Scholar 

  • Steingrover R, Pogány K, Garcia EF, Jurriaans S, Brinkman K, et al. HIV-1 viral rebound dynamics after a single treatment interruption depends on time of initiation of highly active antiretroviral therapy. AIDS (London, England). 2008;22(13):1583–8.

    Article  CAS  Google Scholar 

  • Sthör W, Fidler S, McClure M, Weber J, Cooper D, et al. Duration of HIV-1 viral suppression on cessation of antiretroviral therapy in primary infection correlates with time on therapy. PLoS One. 2013;8(10):e78287.

    Article  Google Scholar 

  • Svicher V, Ceccherini-Silberstein F, Antinori A, Aquaro S, Perno CF. Understanding HIV compartments and reservoirs. Curr HIV/AIDS Rep. 2014;11:186–94.

    Article  PubMed  Google Scholar 

  • Zayyad Z, Spudich S. Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep. 2015;12(1):16–24.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Emory University School of Medicine, 1364 Clifton Road, Atlanta, GA, 30322, USA

    Sol Aldrete & Vincent C. Marconi

Authors
  1. Sol Aldrete
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent C. Marconi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincent C. Marconi .

Editor information

Editors and Affiliations

  1. Dept. Cell & Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA

    Thomas J. Hope

  2. Office of Graduate and Postdoctoral Studies, University of Miami, Miller School of Medicine, Miami, Florida, USA

    Mario Stevenson

  3. University of California, San Diego Dept. Pathology, La Jolla, California, USA

    Douglas Richman

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this entry

Cite this entry

Aldrete, S., Marconi, V.C. (2016). HIV Compartments and Viral Rebound During Treatment Interruption. In: Hope, T., Stevenson, M., Richman, D. (eds) Encyclopedia of AIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9610-6_433-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-9610-6_433-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-9610-6

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation