HIV-1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy

Ortiz, Gabriel M.; Nixon, Douglas F.; Trkola, Alexandra; Binley, James Μ.; Jin, Xia; Bonhoeffer, Sebastian; Kuebler, Peter; Donahoe, Sean M.; Demoitié, Marie-Ange; Kakimoto, William M.; Ketas, Tom; Clas, Brian; Heymann, Jonas J.; Zhang, Linqi; Cao, Yunzhen; Hurley, Arlene; Moore, John P.; Ho, David D.; Markowitz, Martin

doi:10.1172/jci7371

Cited by 218 publications

(128 citation statements)

References 31 publications

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“…This response could perhaps be strengthened to control the virus more effectively. Serial interruptions of antiviral therapy have been shown to achieve this goal (47,48). However, controlled immunotherapeutic protocols associated with HAART may be a safer option.…”

Section: Discussionmentioning

confidence: 99%

Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

Dalod

Dupuis²,

Deschemin³

et al. 1999

J. Clin. Invest.

131

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HIV-specific CD8 + T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8 + T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0-6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1-13). The frequency of HIV-specific CD8 + T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8 + CD28 -terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination.

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Section: Discussionmentioning

confidence: 99%

Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

Dalod

Dupuis²,

Deschemin³

et al. 1999

J. Clin. Invest.

131

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“…Indeed, it was recently suggested that strong virusspecific immune responses could be associated with the rare patient in whom HIV replication remains contained after the discontinuation of HAART. 39 It was also proposed that a broad T-cell response would be more efficient at containing HIV spread than a response focused on few HIV epitopes. 40 We, therefore, suggest that in future studies, Immunoscope analysis should be coupled to functional tests to further characterize the amplitude and the qualitative nature of the T-cell responses elicited by immunization.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of CD8+ T-cell expansions in patients with human immunodeficiency virus infection receiving highly active combination therapy

Gorochov

Neumann

Parizot

et al. 2001

Blood

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“…This qualitative feature enables us to more accurately model patients such as the "Berlin Patient" [18], who interrupted treatment twice and then controlled viral infection without further need for drugs, or some of those referenced by the extensive STI literature summary offered by Bajaria, et al [3], which points to examples in which some patients have developed immune responses sufficient to control infection whereas in others the virus rebounded and again decimated the immune system. For example, in a study of HAART discontinuation [22], three of six patients successfully suppressed plasma virus for four to more than twenty-four months after stopping treatment. These patients exhibited comprehensive and strong HIV-specific immune responses, which are believed responsible for containment of the infection.…”

Section: Optimal Multidrug Therapies: Model Formulationmentioning

confidence: 99%

Dynamic Multidrug Therapies for HIV: Optimal and STI Control Approaches

Adams

Banks²,

Kwon³

et al. 2004

Mathematical Biosciences and Engineering

173

123

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We formulate a dynamic mathematical model that describes the interaction of the immune system with the human immunodeficiency virus (HIV) and that permits drug "cocktail" therapies. We derive HIV therapeutic strategies by formulating and analyzing an optimal control problem using two types of dynamic treatments representing reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Continuous optimal therapies are found by solving the corresponding optimality systems. In addition, using ideas from dynamic programming, we formulate and derive suboptimal structured treatment interruptions (STI) in antiviral therapy that include drug-free periods of immune-mediated control of HIV. Our numerical results support a scenario in which STI therapies can lead to long term control of HIV by the immune response system after discontinuation of therapy.

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HIV-1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy

Cited by 218 publications

References 31 publications

Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

Down-regulation of CD8+ T-cell expansions in patients with human immunodeficiency virus infection receiving highly active combination therapy

Dynamic Multidrug Therapies for HIV: Optimal and STI Control Approaches

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