No Differences of Immune Activation and Microbial Translocation Among HIV-infected Children Receiving Combined Antiretroviral Therapy or Protease Inhibitor Monotherapy

Falcón-Neyra, Lola; BenMarzouk-Hidalgo, Omar J.; Madrid, Lola; Noguera-Julián, Antoni; Fortuny, Clàudia; Neth, Olaf; López‐Cortés, Luis F.

doi:10.1097/md.0000000000000521

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…However, despite ART, there is incomplete immune reconstitution due to the persistent immune activation, although at a lower level. 23 – 28 Furthermore, some patients cannot tolerate therapy, due to cytotoxicity caused by the available ART drugs, 29 , 30 and in others, nonadherence to the treatment regimen or development of resistance to the drugs constitutes a limiting factor in controlling the infection. 31 , 32 In a recent study, we have reported mutations in the reverse transcriptase and protease genes of the virus from both antiretroviral naïve (ART) and treated HIV-1 infected children.…”

Section: Introductionmentioning

confidence: 99%

IL-8 Alterations in HIV-1 Infected Children With Disease Progression

et al. 2016

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Section: Introductionmentioning

confidence: 99%

IL-8 Alterations in HIV-1 Infected Children With Disease Progression

et al. 2016

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“…Extrapolating from adult data would suggest that heightened IA would be an essential component of chronic HIV infection here too; however, it has not been well-characterized. Previous studies have investigated IA in this younger population [16–24]; however, there is limited prior research comprehensively investigated HIV-related and non-HIV-related factors associated with IA in HIV-infected youth.…”

Section: Introductionmentioning

confidence: 99%

Increased Immune Activation and Exhaustion in HIV-infected Youth

Eckard

Rosebush

Lee

et al. 2016

Pediatric Infectious Disease Journal

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Background Immune activation and exhaustion drive several co-morbidities and disease progression in HIV-infected adults; however, they are not well-studied in HIV-infected youth. Thus, this study sought to examine levels of immune activation and exhaustion in this population, investigate associated HIV- and non-HIV-related variables, and compare results with a matched healthy control group. Methods HIV-infected youth 8–25 years old on stable antiretroviral therapy with an HIV-1 RNA level <1000 copies/mL were enrolled, along with matched healthy controls. We measured T-cell and monocyte immune activation and exhaustion markers in cryopreserved PBMC and plasma samples. Results 136 subjects (80 HIV+: 66% male; 91% black) were enrolled. Markers of CD4+ and CD8+ T-cell activation were higher in the HIV-infected group vs. controls [mean % CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ = 2.2 vs. 1.5 (P=0.002) and 4.9 vs. 2.2 (P<0.0001), respectively], as were exhausted CD4+ and CD8+ T-cells [mean % CD4+CD38+HLA-DR+PD-1+ and CD8+CD38+HLA-DR+PD-1+ = 1.0 vs. 0.5 (P<0.0001) and 1.6 vs. 0.7 (P<0.0001), respectively]. There were no differences in proportions of inflammatory or patrolling monocytes between groups (P>0.05); however, soluble CD14 was higher in HIV-infected compared with controls (1.6 vs. 1.4 μg/mL; P=0.01). Current CD4 count, low-density lipoprotein cholesterol, and age were the variables most associated with CD4+ and CD8+ T-cell activation. Conclusions CD4+ and CD8+ T-cell immune activation and exhaustion are higher in HIV-infected youth compared with matched controls, while monocyte sub-populations are not altered despite a high soluble CD14 level. The clinical significance of the increased immune activation and exhaustion should be further explored.

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“…Subjects with previous virological failure (VF) while on a PI-containing regimen were included if the genotypic resistance tests showed no major (I47V, I50V, I54M/L, L76V and I84V) or ≤3 minor resistance mutations associated with reduced susceptibility to DRV according to the 2014 International AIDS Society criteria [11]. The prescription of mtDRV cobi was based on the criteria of the attending physicians as part of their daily clinical practice based on the encouraging results of several clinical trials [12][13][14][15][16][17] and personal experience on boosted-PI monotherapy [18][19][20][21][22][23][24][25][26][27][28], with the objective of avoiding toxicity associated with nucleoside analogues, increasing adherence, and to augment the cost-effectiveness of therapy [29]. Inclusion was not dependent on CD4 + T cell counts, hepatitis C virus (HCV) coinfection, laboratory parameters or the presence of viral blips during the previous 12 months.…”

Section: Methodsmentioning

confidence: 99%

Darunavir/cobicistat showing similar effectiveness as darunavir/ritonavir monotherapy despite lower trough concentrations

et al. 2018

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IntroductionWhen darunavir (DRV) 800 mg is boosted with 150 mg cobicistat (DRV cobi), DRV trough concentration (Ctrough) is about 30% lower as compared to 100 mg ritonavir (DRV rtv). DRV cobi shows similar virological efficacy as DRV rtv when combined with two nucleos(t)ide analogue reverse‐transcriptase inhibitors, but it is unknown whether a lower DRV Ctrough would undermine the effectiveness of DRV cobi when given as monotherapy (mtDRV cobi).MethodsProspective observational study on virologically suppressed HIV‐infected subjects who switched to mtDRV cobi. Virological failure was defined as two consecutive HIV‐RNA >200 copies/mL. Efficacy was evaluated by intention‐to‐treat (ITT) and on‐treatment (OT) analyses, and compared with data from a previous cohort of subjects on mtDRV rtv conducted at our centre. Plasma DRV Ctrough was measured using LC–MS/MS.ResultsA total of 234 subjects were enrolled. At week 96, the efficacy rates were 67.8% (CI 95, 61.8 to 73.7) by ITT and 86.9% (CI 95, 78.0 to 87.7) by OT analyses. The corresponding rates in our historical DRV rtv controls were 67.6% (CI 95, 60.0 to 75.2) and 83.6% (CI 95: 77.2 to 90.0). A total of 135 DRV determinations were performed in 83 subjects throughout the follow‐up period, with a median plasma DRV Ctrough of 1305 ng/mL (range, 150 to 5895) compared with 1710 ng/mL (range, 200 to 3838) in subjects on monotherapy with DRV rtv (p = 0.05).Conclusions DRV Ctrough was lower in HIV‐infected subjects receiving DRV cobi than with DRV rtv. However, this did not appear to influence the efficacy of DRV cobi, when administered as monotherapy.

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No Differences of Immune Activation and Microbial Translocation Among HIV-infected Children Receiving Combined Antiretroviral Therapy or Protease Inhibitor Monotherapy

Cited by 4 publications

References 15 publications

IL-8 Alterations in HIV-1 Infected Children With Disease Progression

IL-8 Alterations in HIV-1 Infected Children With Disease Progression

Increased Immune Activation and Exhaustion in HIV-infected Youth

Darunavir/cobicistat showing similar effectiveness as darunavir/ritonavir monotherapy despite lower trough concentrations

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