Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy
Background: Chronic HIV is associated with increased inflammation and tissue fibrosis despite suppressive antiretroviral therapy (ART). Monocytes and macrophages have been implicated in the pathogenesis of fibrosis, facilitated by chemokine receptor interactions. Methods: We assessed systemic fibrot...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-09-01
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| Series: | HIV Research & Clinical Practice |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/25787489.2020.1719319 |
| _version_ | 1797661033280569344 |
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| author | S. Bowler C. Siriwardhana B. L. Mitchell M. L. D’Antoni D. Ogata-Arakaki S. Souza R. Yee L. M. A. Gangcuangco D. C. Chow L. C. Ndhlovu C. Shikuma |
| author_facet | S. Bowler C. Siriwardhana B. L. Mitchell M. L. D’Antoni D. Ogata-Arakaki S. Souza R. Yee L. M. A. Gangcuangco D. C. Chow L. C. Ndhlovu C. Shikuma |
| author_sort | S. Bowler |
| collection | DOAJ |
| description | Background: Chronic HIV is associated with increased inflammation and tissue fibrosis despite suppressive antiretroviral therapy (ART). Monocytes and macrophages have been implicated in the pathogenesis of fibrosis, facilitated by chemokine receptor interactions. Methods: We assessed systemic fibrotic biomarkers (transforming growth factor beta-1 [TGF-β1], thrombospondin-1 [TSP-1], C-terminal pro-peptide of collagen type I [CICP], and IL-11) in banked plasma from a previously published 24-week open-label trial of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, among persons living with HIV (PLWH) on stable ART with undetectable plasma HIV RNA (<50 copies/mL). Fibrotic markers were assessed by ELISA and Luminex. Untreated HIV-seronegative individuals (n = 6) of similar age and demographics served as a comparator group. Results: Median age of PLWH was 55 years. At baseline, PLWH had higher median TGF-β1 (2.11 vs 1.62 ng/mL, p = 0.01), TSP-1 (236.74 vs 83.29 ng/mL, p < 0.0001), and CICP (200.46 vs 111.28 ng/mL, p = 0.01), but lower IL-11 (36.00 vs 53.74 pg/mL, p = 0.01) compared to HIV-uninfected individuals. Over 24 weeks, median TGF-β1 (-0.74 ng/mL, p = 0.006), TSP-1 (-52.12 ng/mL, p < 0.0001), and CICP (-28.12 ng/mL, p < 0.0001) decreased and IL-11 (28.98 pg/mL, p < 0.0001) increased in PLWH. At week 24, TGF-β1, CICP, and IL-11 were similar between the two groups (p > 0.05), while TSP-1 remained elevated in PLWH (p = 0.009) compared to controls. Conclusions: PLWH had higher levels of the plasma fibrotic markers TGF-β1, TSP-1, and CICP. After 24 weeks of CVC, fibrotic markers generally returned to levels comparable to HIV-uninfected controls. Dual CCR2 and CCR5 blockade may ameliorate the detrimental fibrotic events that persist in treated HIV. |
| first_indexed | 2024-03-11T18:39:31Z |
| format | Article |
| id | doaj.art-1943ada5fcc04469a972bdd3be6591bc |
| institution | Directory Open Access Journal |
| issn | 2578-7470 |
| language | English |
| last_indexed | 2024-03-11T18:39:31Z |
| publishDate | 2019-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | HIV Research & Clinical Practice |
| spelling | doaj.art-1943ada5fcc04469a972bdd3be6591bc2023-10-12T13:43:52ZengTaylor & Francis GroupHIV Research & Clinical Practice2578-74702019-09-01204-512312910.1080/25787489.2020.17193191719319Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapyS. Bowler0C. Siriwardhana1B. L. Mitchell2M. L. D’Antoni3D. Ogata-Arakaki4S. Souza5R. Yee6L. M. A. Gangcuangco7D. C. Chow8L. C. Ndhlovu9C. Shikuma10University of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaUniversity of Hawaii at ManoaBackground: Chronic HIV is associated with increased inflammation and tissue fibrosis despite suppressive antiretroviral therapy (ART). Monocytes and macrophages have been implicated in the pathogenesis of fibrosis, facilitated by chemokine receptor interactions. Methods: We assessed systemic fibrotic biomarkers (transforming growth factor beta-1 [TGF-β1], thrombospondin-1 [TSP-1], C-terminal pro-peptide of collagen type I [CICP], and IL-11) in banked plasma from a previously published 24-week open-label trial of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, among persons living with HIV (PLWH) on stable ART with undetectable plasma HIV RNA (<50 copies/mL). Fibrotic markers were assessed by ELISA and Luminex. Untreated HIV-seronegative individuals (n = 6) of similar age and demographics served as a comparator group. Results: Median age of PLWH was 55 years. At baseline, PLWH had higher median TGF-β1 (2.11 vs 1.62 ng/mL, p = 0.01), TSP-1 (236.74 vs 83.29 ng/mL, p < 0.0001), and CICP (200.46 vs 111.28 ng/mL, p = 0.01), but lower IL-11 (36.00 vs 53.74 pg/mL, p = 0.01) compared to HIV-uninfected individuals. Over 24 weeks, median TGF-β1 (-0.74 ng/mL, p = 0.006), TSP-1 (-52.12 ng/mL, p < 0.0001), and CICP (-28.12 ng/mL, p < 0.0001) decreased and IL-11 (28.98 pg/mL, p < 0.0001) increased in PLWH. At week 24, TGF-β1, CICP, and IL-11 were similar between the two groups (p > 0.05), while TSP-1 remained elevated in PLWH (p = 0.009) compared to controls. Conclusions: PLWH had higher levels of the plasma fibrotic markers TGF-β1, TSP-1, and CICP. After 24 weeks of CVC, fibrotic markers generally returned to levels comparable to HIV-uninfected controls. Dual CCR2 and CCR5 blockade may ameliorate the detrimental fibrotic events that persist in treated HIV.http://dx.doi.org/10.1080/25787489.2020.1719319hivinflammationfibrosischemokinesccr2ccr5 |
| spellingShingle | S. Bowler C. Siriwardhana B. L. Mitchell M. L. D’Antoni D. Ogata-Arakaki S. Souza R. Yee L. M. A. Gangcuangco D. C. Chow L. C. Ndhlovu C. Shikuma Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy HIV Research & Clinical Practice hiv inflammation fibrosis chemokines ccr2 ccr5 |
| title | Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy |
| title_full | Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy |
| title_fullStr | Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy |
| title_full_unstemmed | Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy |
| title_short | Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy |
| title_sort | cenicriviroc a dual ccr2 and ccr5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with hiv on antiretroviral therapy |
| topic | hiv inflammation fibrosis chemokines ccr2 ccr5 |
| url | http://dx.doi.org/10.1080/25787489.2020.1719319 |
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