Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy
Objectives: The interaction between HIV and the immune system gives rise to a complex dynamical system. We therefore investigate whether delayed viral rebound after antiretroviral therapy (ART) interruption (ATI) may be due to an individual's viral-immune state being in a region of relative sta...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-04-01
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| Series: | Journal of Virus Eradication |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2055664020302508 |
| _version_ | 1818719800933744640 |
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| author | John M. Murray |
| author_facet | John M. Murray |
| author_sort | John M. Murray |
| collection | DOAJ |
| description | Objectives: The interaction between HIV and the immune system gives rise to a complex dynamical system. We therefore investigate whether delayed viral rebound after antiretroviral therapy (ART) interruption (ATI) may be due to an individual's viral-immune state being in a region of relative stability, and if so, how this can be extended. Methods: Using a mathematical model duplicating plasma viral levels, HIV DNA and immune homeostatic dynamics for individuals on ART commenced at either primary (PHI) or chronic (CHI) HIV infection, we investigate whether latent reservoir reductions and perturbations in other infected and uninfected memory CD4+ T cell subsets can delay viral rebound. Results: Solely decreasing the latent reservoir did not delay rebound unless ART was commenced at PHI. If ART was commenced at CHI, latent reservoir reductions paired with depletions of each of uninfected resting and activated cells could delay rebound indefinitely. Starting ART at PHI resulted in easier suppression if the reservoir was reduced in combination with each of six infected and uninfected subsets. Although these paired reductions maintained viral suppression, an opportunistic infection that increased activation to suitably high levels can lead to viral rebound. Conclusions: If viral rebound is purely a stochastic process, suppression after an ATI requires reduction of the latent reservoir to extremely low levels. On the other hand, if suppression of the viral-immune system is due to stability properties of this complex system, then achievable latent reservoir reductions can lead to long-term suppression if combined with other cell subset modifications. |
| first_indexed | 2024-12-17T20:12:42Z |
| format | Article |
| id | doaj.art-e02b7928b4284aea890e3ba4a7e7bfd4 |
| institution | Directory Open Access Journal |
| issn | 2055-6640 |
| language | English |
| last_indexed | 2024-12-17T20:12:42Z |
| publishDate | 2018-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Virus Eradication |
| spelling | doaj.art-e02b7928b4284aea890e3ba4a7e7bfd42022-12-21T21:34:12ZengElsevierJournal of Virus Eradication2055-66402018-04-01429198Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapyJohn M. Murray0School of Mathematics and Statistics, UNSW Australia, Sydney, ustralia; Cancer Research Division, NSW Cancer Council, Australia; Corresponding author:John Murray, School of Mathematics and Statistics, UNSW Australia, Sydney, NSW 2052, AustraliaObjectives: The interaction between HIV and the immune system gives rise to a complex dynamical system. We therefore investigate whether delayed viral rebound after antiretroviral therapy (ART) interruption (ATI) may be due to an individual's viral-immune state being in a region of relative stability, and if so, how this can be extended. Methods: Using a mathematical model duplicating plasma viral levels, HIV DNA and immune homeostatic dynamics for individuals on ART commenced at either primary (PHI) or chronic (CHI) HIV infection, we investigate whether latent reservoir reductions and perturbations in other infected and uninfected memory CD4+ T cell subsets can delay viral rebound. Results: Solely decreasing the latent reservoir did not delay rebound unless ART was commenced at PHI. If ART was commenced at CHI, latent reservoir reductions paired with depletions of each of uninfected resting and activated cells could delay rebound indefinitely. Starting ART at PHI resulted in easier suppression if the reservoir was reduced in combination with each of six infected and uninfected subsets. Although these paired reductions maintained viral suppression, an opportunistic infection that increased activation to suitably high levels can lead to viral rebound. Conclusions: If viral rebound is purely a stochastic process, suppression after an ATI requires reduction of the latent reservoir to extremely low levels. On the other hand, if suppression of the viral-immune system is due to stability properties of this complex system, then achievable latent reservoir reductions can lead to long-term suppression if combined with other cell subset modifications.http://www.sciencedirect.com/science/article/pii/S2055664020302508latent reservoirantiretroviral therapyviral reboundmathematical modelstable suppression |
| spellingShingle | John M. Murray Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy Journal of Virus Eradication latent reservoir antiretroviral therapy viral rebound mathematical model stable suppression |
| title | Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy |
| title_full | Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy |
| title_fullStr | Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy |
| title_full_unstemmed | Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy |
| title_short | Latent HIV dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy |
| title_sort | latent hiv dynamics and implications for sustained viral suppression in the absence of antiretroviral therapy |
| topic | latent reservoir antiretroviral therapy viral rebound mathematical model stable suppression |
| url | http://www.sciencedirect.com/science/article/pii/S2055664020302508 |
| work_keys_str_mv | AT johnmmurray latenthivdynamicsandimplicationsforsustainedviralsuppressionintheabsenceofantiretroviraltherapy |