Proscovia M Namuwenge

Purpose: Plasma 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. Methods: Plasma 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. Results: The 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. Conclusion: A 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.

Among HIV-infected adults attending non-governmental organization voluntary counseling and testing (VCT) sites in Uganda that provide a nine-month course of isoniazid preventive treatment (IPT), we report on loss to follow-up (LTFU) and its associated risk factors. The design was a retrospective cohort study of program data spanning a three year period (2006-2008). A total of 586 IPT patients were enrolled of whom 335 (57.1%) were females with a mean age of 34 years. Of those starting IPT, 341 (58.1%) were lost to follow-up, 197 (33.6%) completed IPT, 29 (4.9%) were discontinued and 19 (3.2%) died. The return rates at one, three, five and seven months were 78.0% (457), 62.1% (364), 52.9% (310) and 33.6% (197) respectively. Being less than 30 years of age, widowed, separated, or divorced were found to be associated with a higher risk of loss to follow-up. Sudden improvement in retention on IPT was observed between the years 2006 and 2007, although causes of the improvement are poorly understood hence the need for more research. At non-governmental VCT sites in Uganda, six out of ten individuals enrolled on IPT are lost to follow-up and efforts to reduce this attrition including systems strengthening might play a critical role in the success of IPT programs.