HIV-1 Reservoirs During Suppressive Therapy

Barton, Kirston; Winckelmann, Anni; Palmer, Sarah

doi:10.1016/j.tim.2016.01.006

Cited by 109 publications

(119 citation statements)

References 97 publications

(104 reference statements)

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“…The reservoir is established early in infection (31) and has an estimated t 1/2 of 44 mo (2, 3). Several mechanisms have been proposed to account for the persistence of this reservoir, including low-level viral replication, the long t 1/2 of latently infected cells, and the proliferative expansion of these latently infected cells (5,32,33). Arguments against persistent low-level viral replication include the observation that further intensification of ART has no measurable effect (34,35).…”

Section: Discussionmentioning

confidence: 99%

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

Lorenzi

Cohen

Cohn

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

164

219

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HIV-1–infected individuals harbor a latent reservoir of infected CD4+ T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four fully ART-suppressed, chronically infected individuals were assayed at two time points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging from the latent reservoir showed gp160 env sequences that were identical to at least one other virus. Moreover, 43% of the env sequences from viruses emerging from the reservoir were part of identical groups at the two time points. Groups of identical expanded sequences made up 54% of proviral DNA, and, as might be expected, the sequences of replication-competent viruses in the active reservoir showed limited overlap with integrated proviral DNA, most of which is known to represent defective viruses. Finally, there was an inverse correlation between proviral DNA clone size and the probability of reactivation, suggesting that replication-competent viruses are less likely to be found among highly expanded provirus-containing cell clones.

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Section: Discussionmentioning

confidence: 99%

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

Lorenzi

Cohen

Cohn

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

164

219

View full text Add to dashboard Cite

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“…The complete elimination of virus-infected cells from the host is a laudable goal. However, practical and effective viral eradication strategies do not yet exist for animals or humans infected with lentiviruses in spite of highly effective viral suppression therapies and several decades of research focused on the pathogenesis of lentiviral agents [13]. The identification of permissive cell types and anatomical compartments harbouring virus have been important goals in research related to immunodeficiency-inducing lentiviruses.…”

Section: Feline Immunodeficiency Virus (Fiv) Is a Lentivirus That Shamentioning

confidence: 99%

“…Such information is critical to the development of effective eradication therapies which depend upon the tissue penetration of various pharmaceutical agents. The relative importance of the specific cell types and anatomical compartments that constitute the lentiviral reservoir in an infected host remain controversial [13,14].…”

Section: Feline Immunodeficiency Virus (Fiv) Is a Lentivirus That Shamentioning

confidence: 99%

“…Multiple factors play roles in defining a cell's permissiveness to lentiviral infection and productive replication and include the appropriate membrane receptors for virus attachment, fusion and entry, a temporally appropriate milieu of nuclear transcription factors, activation state, target cell subset, tissue micro-environment, and presence of specific host cellular restriction factors like tetherin, APOBEC3 family and others [11,13,15,16]. These same factors also determine the identity of cells that serve as reservoirs for persistent latent virus [13].…”

Section: Feline Immunodeficiency Virus (Fiv) Is a Lentivirus That Shamentioning

confidence: 99%

“…These same factors also determine the identity of cells that serve as reservoirs for persistent latent virus [13].…”

Section: Feline Immunodeficiency Virus (Fiv) Is a Lentivirus That Shamentioning

confidence: 99%

See 2 more Smart Citations

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Eckstrand

Sparger

Murphy

2017

Journal of General Virology

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Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human immunodeficiency virus (HIV), results in lifelong viral persistence and progressive immunopathology in the cat. FIV has the ability to infect and produce infectious virus in a number of different cell types. FIV provirus can also be maintained in a replication-competent but transcriptionally quiescent state, facilitating viral persistence over time. Immediately after the initial infection, FIV infection quickly disseminates to many anatomical compartments within the host including lymphoid organs, gastrointestinal tract and brain. Collectively, the anatomic and cellular compartments that harbour FIV provirus constitute the viral reservoir and contain foci of both ongoing viral replication and transcriptionally restricted virus that may persist over time. The relative importance of the different phenotypes observed for infected cells, anatomic compartment, replication status and size of the reservoir represent crucial areas of investigation for developing effective viral suppression and eradication therapies. In this review, we discuss what is currently known about FIV reservoirs, and emphasize the utility of the FIV-infected cat as a model for the HIV-infected human.

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Pharmaceutical Approaches to HIV Treatment and Prevention

Yavuz

Morgan

Showalter

et al. 2018

Advanced Therapeutics

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Human immunodeficiency virus (HIV) infection continues to pose a major infectious disease threat worldwide. It is characterized by the depletion of CD4 + T cells, persistent immune activation, and increased susceptibility to secondary infections. Advances in the development of antiretroviral drugs and combination antiretroviral therapy have resulted in a remarkable reduction in HIV-associated morbidity and mortality. Antiretroviral therapy (ART) leads to effective suppression of HIV replication with partial recovery of host immune system and has successfully transformed HIV infection from a fatal disease to a chronic condition. Additionally, antiretroviral drugs have shown promise for prevention in HIV pre-exposure prophylaxis and treatment as prevention. However, ART is unable to cure HIV. Other limitations include drug-drug interactions, drug resistance, cytotoxic side effects, cost, and adherence. Alternative treatment options are being investigated to overcome these challenges including discovery of new molecules with increased anti-viral activity and development of easily administrable drug formulations. In light of the difficulties associated with current HIV treatment measures, and in the continuing absence of a cure, the prevention of new infections has also arisen as a prominent goal among efforts to curtail the worldwide HIV pandemic. In this review, the authors summarize currently available anti-HIV drugs and their combinations for treatment, new molecules under clinical development and prevention methods, and discuss drug delivery formats as well as associated challenges and alternative approaches for the future.

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HIV-1 Reservoirs During Suppressive Therapy

Cited by 109 publications

References 97 publications

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Pharmaceutical Approaches to HIV Treatment and Prevention

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