scholarly journals Population Pharmacokinetics of Tenofovir in Human Immunodeficiency Virus-Infected Patients Taking Highly Active Antiretroviral Therapy

2005 ◽  
Vol 49 (8) ◽  
pp. 3361-3366 ◽  
Author(s):  
Vincent Jullien ◽  
Jean-Marc Tréluyer ◽  
Elisabeth Rey ◽  
Patrick Jaffray ◽  
Anne Krivine ◽  
...  

ABSTRACT The influence of renal function on tenofovir pharmacokinetics was investigated in 193 human immunodeficiency virus (HIV)-infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM. Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Typical population estimates of apparent central distribution volume (Vc /F), peripheral distribution volume (Vp /F), intercompartmental clearance (Q/F), and plasma clearance (CL/F) were 534 liters, 1,530 liters, 144 liters/h and 90.9 liters/h, respectively. Apparent plasma clearance was related to body weight/serum creatinine ratio (BW/SCR) and to the existence of a tubular dysfunction. Concomitant treatment with lopinavir/ritonavir was found to decrease tenofovir clearance. Individual Bayesian estimates of CL/F were used to calculate the tenofovir area under the concentration-time curve from time zero to 24 h (AUC0-24). In patients without tubular dysfunction, AUC0-24 values markedly decreased from 6.7 to 1.4 mg · h/liter for BW/SCR increasing from 0.44 to 1.73. The relevance of a dosage adjustment based on BW/SCR should be further evaluated.

1998 ◽  
Vol 178 (5) ◽  
pp. 1299-1305 ◽  
Author(s):  
Susanne Dam Nielsen ◽  
Annette Kjær Ersbøll ◽  
Lars Mathiesen ◽  
Jens Ole Nielsen ◽  
John‐Erik Stig Hansen

2001 ◽  
Vol 8 (5) ◽  
pp. 943-948 ◽  
Author(s):  
Vesna Blazevic ◽  
Shirley Jankelevich ◽  
Seth M. Steinberg ◽  
Freda Jacobsen ◽  
Robert Yarchoan ◽  
...  

ABSTRACT The present study analyzes the effect of highly active antiretroviral therapy (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)-infected children over a 24-week period following initiation of HAART with ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included cytokine production by monocytes as well as T-cell proliferation in response to mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides. Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4+ T-cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH) response. At enrollment the children exhibited defects in several immune parameters measured. Therapy increased CD4+ T-cell counts and decreased viral loads significantly. By contrast, the only immunological parameter that was significantly increased was IL-12 p70 production by monocytes; the DTH response to Candida albicans also showed a strong increase in patients becoming positive. In conclusion, these results demonstrate that HAART in HIV-infected children affects the dynamics of HIV replication and the CD4+ T-cell count over 24 weeks, similar to the pattern seen in HIV-infected adults. Furthermore, these data indicate improvement in antigen-presenting cell immunological function in HIV-infected children induced by HAART.


Author(s):  
Adiga Sachidananda Mn ◽  
Adiga Usha S

Objective: Treatment of human immunodeficiency virus (HIV) with highly active antiretroviral therapy is complicated due to its effect on liver enzymes along with associated risk of opportunistic infection and its treatment. The objective of the study was to compare the effect of two zidovudine and lamivudine-based regimens on liver enzymes and to correlate them with age and CD4 count in HIV patients.Methods: In this retrospective study, patients who have received zidovudine+lamivudine+nevirapine (ZLN) or zidovudine+lamivudine+efavirenz (ZLE) at least for 1 year were included. Baseline, 6-month, and 1-year values of aspartate amino transferase (AST), alanine amino transferase (ALT), and CD4 count were collected. One-way analysis of variance and unpaired t-test were used to compare the difference in AST, ALT, and CD4 count value within basal, 6 months, and 1 year of two group and between the groups, respectively. Pearson’s correlation was used for correlation study.Results: Elevation of AST levels in patients who had received ZLN regimen at different interval was significant statistically. There was a statistically significant elevation of ALT level at 6 months. There was no significant change in AST and ALT values in patients who had received ZLE regimen. Between the two regimens, there was statistically significant difference in AST and ALT values at 6 months and 1 year. There was no correlation between age and CD4 count with liver enzymes.Conclusion: We conclude from the study that nevirapine containing zidovudine regimen showed a slight elevation in AST. The efavirenz regimen did not show a change in AST and ALT.


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