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HIV persistence in the setting of antiretroviral therapy: when, where and how does HIV hide?

Kulpa DA, Chomont N - J Virus Erad (2015)

Bottom Line: In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person.The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV.In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist?

View Article: PubMed Central - PubMed

Affiliation: Vaccine and Gene Therapy Institute Florida, Port St Lucie, Florida, USA.

ABSTRACT

Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals. However, the possible long-term toxicity associated with antiretroviral therapy (ART), stigma and cost, all contribute to the necessity of finding a cure for HIV infection. In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person. These persistently infected cells, usually referred as the 'reservoirs for HIV infection', are the main barriers to a cure. The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV. In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist?

No MeSH data available.


Related in: MedlinePlus

Clinical definition of the HIV reservoir. Untreated HIV infection is characterised by high levels of viral replication that can be measured in the plasma of HIV-infected individuals. ART reduces viral replication to undetectable levels by standard viral load measurements. When ART is interrupted, HIV replication resumes, revealing that HIV persisted in cellular and anatomical ‘reservoirs’ during ART and that these reservoirs can re-ignite infection.
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Figure 1: Clinical definition of the HIV reservoir. Untreated HIV infection is characterised by high levels of viral replication that can be measured in the plasma of HIV-infected individuals. ART reduces viral replication to undetectable levels by standard viral load measurements. When ART is interrupted, HIV replication resumes, revealing that HIV persisted in cellular and anatomical ‘reservoirs’ during ART and that these reservoirs can re-ignite infection.

Mentions: Soon after the implementation of ART in 1996, the possibility that ART initiated very early in infection could prevent the establishment of the long-lived HIV reservoir and shorten the duration of HIV persistence after prolonged therapy was proposed [8]. The rationale for this intervention originates from the fact that the latent reservoir is not created but rather revealed by ART, as latently infected CD4+ T cells are generated during untreated HIV infection (Figure 1). Therefore, a reasonable hypothesis is that by reducing the duration of exposure to the virus through early ART initiation, one would limit the overall number of infected cells, thereby reducing the possibility for some of them to revert to a resting state or to directly establish latency.


HIV persistence in the setting of antiretroviral therapy: when, where and how does HIV hide?

Kulpa DA, Chomont N - J Virus Erad (2015)

Clinical definition of the HIV reservoir. Untreated HIV infection is characterised by high levels of viral replication that can be measured in the plasma of HIV-infected individuals. ART reduces viral replication to undetectable levels by standard viral load measurements. When ART is interrupted, HIV replication resumes, revealing that HIV persisted in cellular and anatomical ‘reservoirs’ during ART and that these reservoirs can re-ignite infection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593515&req=5

Figure 1: Clinical definition of the HIV reservoir. Untreated HIV infection is characterised by high levels of viral replication that can be measured in the plasma of HIV-infected individuals. ART reduces viral replication to undetectable levels by standard viral load measurements. When ART is interrupted, HIV replication resumes, revealing that HIV persisted in cellular and anatomical ‘reservoirs’ during ART and that these reservoirs can re-ignite infection.
Mentions: Soon after the implementation of ART in 1996, the possibility that ART initiated very early in infection could prevent the establishment of the long-lived HIV reservoir and shorten the duration of HIV persistence after prolonged therapy was proposed [8]. The rationale for this intervention originates from the fact that the latent reservoir is not created but rather revealed by ART, as latently infected CD4+ T cells are generated during untreated HIV infection (Figure 1). Therefore, a reasonable hypothesis is that by reducing the duration of exposure to the virus through early ART initiation, one would limit the overall number of infected cells, thereby reducing the possibility for some of them to revert to a resting state or to directly establish latency.

Bottom Line: In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person.The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV.In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist?

View Article: PubMed Central - PubMed

Affiliation: Vaccine and Gene Therapy Institute Florida, Port St Lucie, Florida, USA.

ABSTRACT

Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals. However, the possible long-term toxicity associated with antiretroviral therapy (ART), stigma and cost, all contribute to the necessity of finding a cure for HIV infection. In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person. These persistently infected cells, usually referred as the 'reservoirs for HIV infection', are the main barriers to a cure. The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV. In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist?

No MeSH data available.


Related in: MedlinePlus