Viral and Latent Reservoir Persistence in HIV-1--Infected Patients on Therapy

Hwijin Kim; Perelson, Alan S.
October 2006
PLoS Computational Biology;Oct2006, Vol. 2 Issue 10, p1232
Academic Journal
Despite many years of potent antiretroviral therapy, latently infected cells and low levels of plasma virus have been found to persist in HIV-infected patients. The factors influencing this persistence and their relative contributions have not been fully elucidated and remain controversial. Here, we address these issues by developing and employing a simple, but mechanistic viral dynamics model. The model has two novel features. First, it assumes that latently infected T cells can undergo bystander proliferation without transitioning into active viral production. Second, it assumes that the rate of latent cell activation decreases with time on antiretroviral therapy due to the activation and subsequent loss of latently infected cells specific for common antigens, leaving behind cells that are successively less frequently activated. Using the model, we examined the quantitative contributions of T cell bystander proliferation, latent cell activation, and ongoing viral replication to the stability of the latent reservoir and persisting low-level viremia. Not surprisingly, proliferation of latently infected cells helped maintain the latent reservoir in spite of loss of latent infected cells through activation and death, and affected viral dynamics to an extent that depended on the magnitude of latent cell activation. In the limit of zero latent cell activation, the latent cell pool and viral load became uncoupled. However, as the activation rate increased, the plasma viral load could be maintained without depleting the latent reservoir, even in the absence of viral replication. The influence of ongoing viral replication on the latent reservoir remained insignificant for drug efficacies above the ‘critical efficacy’ irrespective of the activation rate. However, for lower drug efficacies viral replication enabled the stable maintenance of both the latent reservoir and the virus. Our model and analysis methods provide a quantitative and qualitative framework for probing how different viral and host factors contribute to the dynamics of the latent reservoir and the virus, offering new insights into the principal determinants of their persistence. INSET: Synopsis.


Related Articles

  • Sharp fall in rates of second treatment failure and death after second failure.  // HIV Treatment ALERTS!;Apr2010, p32 

    The article discusses the study conducted in 1996 through 2005 regarding the rates of second treatment failure in people with HIV in the U.S. and Canada. It says that the study covers the assessment of HIV-infected people ages 18 above who underwent antiretroviral therapy wherein their first...

  • Etravirine. Haubrich, Richard; Gubernick, Steven; Yasothan, Uma; Kirkpatrick, Peter // Nature Reviews Drug Discovery;Apr2008, Vol. 7 Issue 4, p287 

    Etravirine (Intelence; Tibotec) is a non-nucleoside inhibitor of HIV-1 reverse transcriptase. In January 2008, it was approved by the US FDA for the treatment of HIV-1 infection in combination with other antiretroviral agents for treatment-experienced patients who have HIV-1 strains that are...

  • A new dawn for antiretrovirals. Sutherland, Rebecca Kay // BMJ: British Medical Journal (International Edition);2/12/2005, Vol. 330 Issue 7487, p371 

    Documents the introduction of antiretroviral drugs to HIV patients in Africa in 2004. Challenges faced by the author in obtaining antiretrovirals for the community he served in South Africa; Clinical progress of those receiving the drugs; Positive effects of antiretroviral treatment, including...

  • US HIV group spends 25% of time with viral load above 1500 copies.  // HIV Treatment ALERTS!;Sep2015, p23 

    The article discusses the time spent by U.S. patients with human immunodeficiency virus (HIV) with viral load in receiving care. Topics covered include the importance of viral load to the transmission of the virus to other people. Also mentioned is the percentage of people who are receiving...

  • Late onset hepatitis and prolonged deterioration in hepatic function associated with nevirapine therapy. Clarke, S.; Harrington, P.; Condon, C.; Kelleher, D.; Smith, O. P.; Mulcahy, F. // International Journal of STD & AIDS;May2000, Vol. 11 Issue 5, p336 

    The aetiology of hepatic dysfunction in patients with HIV infection is multifactorial. Re-activation of hepatitis C infection, drug toxicity, and opportunistic infections are all potential causes. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used as part of combination...

  • The Virologic and Immunologic Effects of Cyclosporine as an Adjunct to Antiretroviral Therapy in Patients Treated during Acute and Early HIV-1 Infection. Markowitz, Martin; Vaida, Florin; Hare, C. Bradley; Boden, Daniel; Mohri, Hiroshi; Hecht, Frederick M.; Kalayjian, Robert C.; Conrad, Ann; Mildvan, Donna; Aberg, Judith; Hogan, Christine; Kilby, J. Michael; Balfour Jr., Henry H.; Schafer, Kim; Richman, Douglas; Little, Susan // Journal of Infectious Diseases;5/1/2010, Vol. 201 Issue 9, p1298 

    Acute human immunodeficiency virus type 1 (HIV-1) infection is characterized by high levels of immune activation. Immunomodulation with cyclosporine combined with antiretroviral therapy (ART) in the setting of acute and early HIV-1 infection has been reported to result in enhanced immune...

  • Immune Status at Presentation to Care Did Not Improve among Antiretroviral-Naive Persons from 1990 to 2006. Keruly, Jeanne C.; Moore, Richard D. // Clinical Infectious Diseases;11/15/2007, Vol. 45 Issue 10, p1369 

    Background. Human immunodeficiency virus (HIV) prevention initiatives to improve access to HIV services have increased over time. Despite this, >250,000 cases of HIV infection in the United States are undiagnosed, and many infected persons do not present for care until their HIV infection is...

  • Use of complementary therapies to treat patients with HIV/AIDS. Palmer, Richard // Nursing Standard;8/20/2008, Vol. 22 Issue 50, p35 

    This article investigates the use of complementary and alternative medicine (CAM) in people living with human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS). Since the beginning of the HIV/AIDS pandemic people living with HIV/AIDS have turned to CAM, either to...

  • The prognostic significance of the results of genotyping human immunodeficiency virus isolated from the patients with primary HIV-infection in 2009 and 2011 in St. Petersburg. Musatov, Vladimir B.; Yakovlev, Alexey A.; Tirgina, Tatiana V.; Ladnaya, Natalia N. // Vestnik Sankt-Peterburgskogo universiteta, Seriia 7: Geologia, G;2013, Issue 1, p251 

    The data on the subtype human immunodeficiency virus, detection rate of primary and secondary mutations in human immunodeficiency virus isolated from patients with primary HIV infection in 2009 and 2011 are presented. 78 samples were investigated. The subtype A virus prevails, which was...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics