Safety, efficacy and indications of prescription of maraviroc in clinical practice: Factors associated with clinical outcomes

Llibre, Josep M; Rivero, Antonio; Rojas, Jhon; Toro, Miguel García del; Herrero, Cristina; Arroyo, David; Pineda, Juan A.; Pasquau, Juan; Masiá, Mar; Crespo, Manel; Blanco, José Ramón; Moreno, Santiago

doi:10.1016/j.antiviral.2015.05.001

Cited by 16 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Individuals carrying the allele show slowed disease progression upon infection with HIV and less cognitive impairment [ 35 – 38 ]. Furthermore, maraviroc, a CCR5 antagonist with relatively high CNS penetrance [ 39 ], reduces microglial activation in the simian immunodeficiency virus-infected model to uninfected control levels and reduces the expression of several pro-inflammatory factors [ 40 ]. cART regimens that are supplemented with maraviroc improve the neurocognitive status of HIV+ patients and reduce CSF levels of TNFα [ 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

A central role for glial CCR5 in directing the neuropathological interactions of HIV-1 Tat and opiates

Kim

Hahn

Podhaizer

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundThe collective cognitive and motor deficits known as HIV-associated neurocognitive disorders (HAND) remain high even among HIV+ individuals whose antiretroviral therapy is optimized. HAND is worsened in the context of opiate abuse. The mechanism of exacerbation remains unclear but likely involves chronic immune activation of glial cells resulting from persistent, low-level exposure to the virus and viral proteins. We tested whether signaling through C-C chemokine receptor type 5 (CCR5) contributes to neurotoxic interactions between HIV-1 transactivator of transcription (Tat) and opiates and explored potential mechanisms.MethodsNeuronal survival was tracked in neuronal and glial co-cultures over 72 h of treatment with HIV-1 Tat ± morphine using cells from CCR5-deficient and wild-type mice exposed to the CCR5 antagonist maraviroc or exogenously-added BDNF (analyzed by repeated measures ANOVA). Intracellular calcium changes in response to Tat ± morphine ± maraviroc were assessed by ratiometric Fura-2 imaging (analyzed by repeated measures ANOVA). Release of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF from CCR5-deficient and wild-type glia was measured by ELISA (analyzed by two-way ANOVA). Levels of CCR5 and μ-opioid receptor (MOR) were measured by immunoblotting (analyzed by Student’s t test).ResultsHIV-1 Tat induces neurotoxicity, which is greatly exacerbated by morphine in wild-type cultures expressing CCR5. Loss of CCR5 from glia (but not neurons) eliminated neurotoxicity due to Tat and morphine interactions. Unexpectedly, when CCR5 was lost from glia, morphine appeared to entirely protect neurons from Tat-induced toxicity. Maraviroc pre-treatment similarly eliminated neurotoxicity and attenuated neuronal increases in [Ca2+]i caused by Tat ± morphine. proBDNF/BDNF ratios were increased in conditioned media from Tat ± morphine-treated wild-type glia compared to CCR5-deficient glia. Exogenous BDNF treatments mimicked the pro-survival effect of glial CCR5 deficiency against Tat ± morphine.ConclusionsOur results suggest a critical role for glial CCR5 in mediating neurotoxic effects of HIV-1 Tat and morphine interactions on neurons. A shift in the proBDNF/BDNF ratio that favors neurotrophic support may occur when glial CCR5 signaling is blocked. Some neuroprotection occurred only in the presence of morphine, suggesting that loss of CCR5 may fundamentally change signaling through the MOR in glia.

show abstract

Section: Introductionmentioning

confidence: 99%

A central role for glial CCR5 in directing the neuropathological interactions of HIV-1 Tat and opiates

Kim

Hahn

Podhaizer

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…MVC has been shown to be of interest in various clinical situations in experienced patients. It has been evaluated in patients with virological failure, and in patients with poor tolerability of NRTI, NNRTI or PI in sparing strategies [3, 7, 8, 15–18]. Studies have also reported a specific interest in patients with poor immune restoration, with greater increase in CD4 T-cells [19, 20].…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, Llibre et al conducted a multicentre retrospective study assessing conditions of MVC prescription between 2012 and 2013. MVC was used in salvage therapy only in half of the cases [15]. Thus, prescription of tropism test should be adapted to the evolution of MVC prescription habits.…”

Section: Discussionmentioning

confidence: 99%

Clinical impact of tropism testing in a real-life cohort of HIV infected patients: a retrospective observational study

et al. 2019

View full text Add to dashboard Cite

Background The circumstances of prescription of tropism tests clinically relevant in treatment-experienced patients are unclear. Methods We performed a monocentric retrospective analysis of all tropism tests performed between 2006 and 2015 in HIV-infected patients on antiretroviral therapy (ART) without MVC. The motivation of tropism determination was collected. Factors associated with MVC prescription were determined using logistic regression analysis. Results Five hundred sixty-three tests were performed in experienced patients not receiving MVC. Reasons for tropism performance were: virological failure (44%), side effects or drug-interactions (37%), simplification or sparing strategies (11%), immunological failure (5%), and improvement of neurological diffusion (3%). MVC was prescribed in 110 cases (20%), though 366 tests (65%) revealed a tropism CCR5. MVC was more often prescribed before 2011 (OR 3.65, 95% CI 2.17–6.13) and in patients with multiple previous ART regimens (less than 4 ART regimens compare to more than 10 ART regimens (OR 0.34, 95% CI 0.15–0.74)). Conclusions In experienced patients not receiving MVC, tropism test prescription should be restricted to patients with virological failure and limited therapeutic options such as patients already treated with a wide range of ART regimens.

show abstract

“…11,12 Additionally, in our study the pretherapy VL was <100 000 copies/mL which has actually been associated with better virologic success in the real-world settings. 13…”

Section: Discussionmentioning

confidence: 99%

High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis—Maraviroc Effectiveness in HIV-1 Subtype C

Pujari¹,

Gaikwad²,

Bele³

et al. 2018

J Int Assoc Provid AIDS Care

View full text Add to dashboard Cite

show abstract

Safety, efficacy and indications of prescription of maraviroc in clinical practice: Factors associated with clinical outcomes

Cited by 16 publications

References 32 publications

A central role for glial CCR5 in directing the neuropathological interactions of HIV-1 Tat and opiates

A central role for glial CCR5 in directing the neuropathological interactions of HIV-1 Tat and opiates

Clinical impact of tropism testing in a real-life cohort of HIV infected patients: a retrospective observational study

High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis—Maraviroc Effectiveness in HIV-1 Subtype C

Contact Info

Product

Resources

About