Abstract
PurposePlasma albumin, a biomarker for hepatic function, is reported to correspondingly decrease in concentration as disease severity increases in chronic infections including HIV and TB. Our objective was to develop a semi-mechanistic disease progression model to quantify plasma albumin concentration changes during TB and HIV therapy and identify the associated covariate factors.MethodsPlasma albumin concentration data was collected at specified times for 3 months from 262 HIV participants receiving efavirenz based anti retroviral therapy. Of these, 158 were TB co-infected and on Rifampicin based anti –tuberculosis co-treatment. An indirect response model with zero order albumin production and first order elimination was developed in NONMEM version 7.2 to describe our data. Genotype (CYP2B6*6 and 11, CYP3A5, ABCB1c.3435C>T and ABCB1rs), TB disease status, baseline age, body weight, plasma creatinine, alanine transaminase enzyme and CD4+ count were the potential model covariates tested.ResultsThe proposed model successfully described plasma albumin concentration changes in the study population. There was a 10.9% and 48.6% increase in albumin production rates in HIV only and TB co-infected participants respectively. Participants co-infected with TB showed a 44.2% lower baseline albumin secretion rate than those without TB while ABCB1c.3435C>T mutation was associated with a 16% higher steady state albumin secretion rate following treatment.ConclusionA semi-mechanistic model describes plasma albumin concentration changes in HIV patients on ART. Further work is required to establish the utility of the model in monitoring disease progression and predicting prognosis in HIV and TB co-infected patients in absence of or during treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s40203-014-0003-9) contains supplementary material, which is available to authorized users.
Highlights
In humans, albumin is the most abundant plasma protein (55-60% of plasma protein) having a normal plasma concentration of 3.5-5 g/dl (Bircher et al 1991)
We developed and validated a semi-mechanistic non-linear mixed effects model describing changes in plasma albumin concentration in Human immunodeficiency virus (HIV) and TB patients
The data consisted of 262 Anti retroviral therapy (ART) naïve HIV patients, 158 of whom were co-infected with tuberculosis
Summary
Albumin is the most abundant plasma protein (55-60% of plasma protein) having a normal plasma concentration of 3.5-5 g/dl (Bircher et al 1991). It is exclusively synthesized in the liver. Reduced plasma albumin concentrations have been reported in states of chronic infection such as TB, HIV, Hep B and C (Olawumi and Olatunji 2006, Akinpelu et al 2012, Zia and Shankar 2012) and as a result, there are suggestions for its use as a prognostic marker in pretreated HIV and TB patients (Feldman et al 2003, Graham et al 2007, Sudfeld et al 2013, Alvarez-Uria et al 2013). Owing to simplicity in terms quantification and low cost of plasma albumin determination, it could substitute CD4+ and viral load tests (Graham et al 2007, Kannangai et al 2008) as a prognostic marker during care for HIV and co morbidities such as TB
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