Influence of viral chronic hepatitis co-infection on plasma drug concentrations and liver transaminase elevations upon therapy switch in HIV-positive patients

Torti, Carlo; Lapadula, Giuseppe; Uccelli, Maria Cristina; Quiros-Roldan, Eugenia; Regazzi, Mario; Ladisa, Nicoletta; Micheli, Valeria; Orani, Anna Maria; Patroni, Andrea; Caputo, Sergio Lo; Tirelli, Valeria; Giambenedetto, Simona Di; Cologni, Giuliana; Costarelli, Silvia; Gargiulo, Franco; Manca, N.; Carosi, Giampiero

doi:10.1016/j.ijantimicag.2006.08.015

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…25 To strengthen this argument further, another study showed that co-infection is associated with higher plasma concentration of antiretrovirals and increased transaminasemia, but the elevation of transaminases was not correlated with drug levels. 26 However, none of the aforementioned studies focused particularly on the incidence of change of treatment combinations. Unfortunately, the two studies (including ours) 5 that used as outcome the rate of ART change lacked the necessary information and failed to investigate the potential differences in the frequency of ART changes attributed to liver toxicity between co-infected patients and individuals infected only with HIV.…”

Section: Discussionmentioning

confidence: 99%

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

et al. 2010

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The current study investigated the impact of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection on the rate of change of antiretroviral drugs after the initiation of highly active antiretroviral treatment (HAART). The data on 1425 HIV-positive patients with recorded serology for hepatitis B surface antigen (HBsAg) were retrospectively analysed. The estimated rate of treatment change was slightly higher in the HBsAg-positive group (0.57 per year) compared with the HBsAg-negative group (0.50 per year). Although this difference was insignificant in multivariable modelling, the confidence intervals of the estimates barely included unity. Antiretroviral drug family, calendar period, prior exposure to antiretrovirals and the diagnosis of acquired immunodeficiency syndrome were independently associated with the number of drug alterations. A slight impact of co-infection on the frequency of treatment change after the beginning of HAART cannot be excluded. However, the paucity of studies on this issue necessitates the conduct of further research.

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Section: Discussionmentioning

confidence: 99%

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

et al. 2010

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“…The cause of these SNAEs seems to be multi-factorial. Aging [ 6 ], high-risk behaviour [ 7 ], co-infections [ 8 ], ART toxicity [ 9 ], CD4+ T cell depletion [ 10 , 11 ], microbial translocation [ 12 ] and immune activation [ 13 – 19 ] all appear to contribute to SNAE pathogenesis. In the ART-treated HIV-1 infected control arm participants in the large, well-characterized trials SMART and ESPRIT [ 20 – 23 ] baseline levels of the soluble markers hs-CRP, D-dimer and IL-6 as well as CD4+ T cell count showed strong associations with mortality [ 24 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study

Murray¹,

Suzuki²,

Law³

et al. 2015

PLoS ONE

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IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

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“…[1–4] These non-AIDS events (including cardiovascular, renal, and hepatic events and non-AIDS cancers) [2–9] are most likely to be multi-factorial in origin, with aging[10], high-risk behavior[11], co-infections[12] and cART toxicity[7] being contributing factors.…”

Section: Introductionmentioning

confidence: 99%

Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients

Achhra

Amin

Law

et al. 2010

Aids

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Objective To investigate the relative predictive value of CD4+ metrics for serious clinical endpoints. Design Observational Methods Patients (3012; 20317 person-years) from control arms of ESPRIT and SILCAAT trials were followed prospectively. We used Cox regression to identify CD4+ metrics (latest, baseline and nadir CD4+count, latest CD4+%, time spent with CD4+count below certain thresholds and CD4+ slopes) independently predictive of i)all-cause mortality; ii) non-AIDS deaths; iii) non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and iv) AIDS events. Akaike Information Criteria (AIC) was calculated for each model. Significant metrics (p<0.05) were then additionally adjusted for latest CD4+ count. Results Non-AIDS deaths occurred at a higher rate than AIDS deaths (rate-ratio: 6.48, 95%CI: 5.1–8.1) and similarly, non-AIDS events (rate-ratio: 1.72, 95%CI: 1.65–1.79). Latest CD4+count was strongly predictive of lower risk of death (HR per log2 rise: 0.48, 95%CI: 0.43–0.54), with lowest AIC of all metrics. CD4+ slope over 7-visits, after additional adjustment for latest CD4+count, was the only metric to be independent predictor for all-cause (HR for slope<-10/mm3/month vs. 0±10: 3.04, 95%CI: 1.98–4.67) and non-AIDS deaths (HR for slope <-10/mm3/month vs. 0±10: 2.62, 95%CI: 1.62–4.22). Latest CD4+ count (per log2 rise) was the best predictor across all endpoints (i–iv) and predicted hepatic (HR: 0.46, 95%CI: 0.33–0.63) and renal events (HR: 0.39, 95%CI: 0.21–0.70), but not cardiovascular events (HR: 1.05, 95%CI: 0.77–1.43) or non-AIDS cancers (HR: 0.78, 95%CI: 0.59–1.03). Conclusion Latest CD4+count is the best predictor of serious endpoints. CD4+ slope independently predicts all-cause and non-AIDS deaths.

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Influence of viral chronic hepatitis co-infection on plasma drug concentrations and liver transaminase elevations upon therapy switch in HIV-positive patients

Cited by 10 publications

References 12 publications

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study

Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients

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