TY - JOUR A1 - Gunda, Daniel W. A1 - Kasang, Christa A1 - Kidenya, Benson R. A1 - Kabangila, Rodrick A1 - Mshana, Stephen E. A1 - Kidola, Jeremiah A1 - Kalluvya, Samuel E. A1 - Kongola, Gilbert W. A1 - Klinker, Hartwig T1 - Plasma Concentrations of Efavirenz and Nevirapine among HIV-Infected Patients with Immunological Failure Attending a Tertiary Hospital in North-Western Tanzania JF - PLOS ONE N2 - Background: Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods: A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results: Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supratherapeutic ARV plasma drug concentrations. Conclusion: There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure. KW - reverse-transcriptase inhibitors KW - randomized controlled-trial KW - routine clinical-practice KW - antiretroviral therapy KW - drug interactions KW - HIV-1-infected patients KW - management KW - indinavir KW - Uganda Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128456 SN - 1932-6203 VL - 8 IS - 9 ER - TY - JOUR A1 - Rudovick, Ladius A1 - Brauner, Jan M. A1 - Englert, Johanna A1 - Seemann, Carolina A1 - Plugaru, Karina A1 - Kidenya, Benson R. A1 - Kalluvya, Samuel E. A1 - Scheller, Carsten A1 - Kasang, Christa T1 - Prevalence of pretreatment HIV drug resistance in Mwanza, Tanzania JF - Journal of Antimicrobial Chemotherapy N2 - Background: In a 2008-10 study, we found a pretreatment HIV drug resistance (PDR) prevalence of 18.2% in patients at Bugando Medical Centre (BMC) in Mwanza, Tanzania. Objectives: To determine the prevalence of PDR and transmitted HIV drug resistance (TDR) in patients visiting the BMC from 2013 to 2015. Methods: Adult outpatients were sequentially enrolled into two groups, separated by whether they were initiating ART. Previous exposure to antiretroviral drugs, except for prevention of mother-to-child transmission, was an exclusion criterion. HIV pol sequences were analysed according to WHO guidelines for surveillance of PDR and TDR. Results: Two hundred and thirty-five sequences were analysed (138 ART initiators, 97 non-initiators). The prevalence of PDR was 4.7% (95% CI 2.6%-8.2%) overall, 3.1% (95% CI 1.1%-8.7%) for non-initiators and 5.8% (95% CI 3.0%-11.0%) for ART initiators. PDR to NNRTIs and nucleoside or nucelotide reverse transcriptase inhibitors was found in 3.0% (95% CI 1.5%-6.0%) and 1.7% (95% CI 0.7%-4.3%) of patients, respectively. Resistance to PIs was not observed. The prevalence of TDR was 6.0% (95% CI 3.6%-9.8%). Conclusions: Prevalence of PDR significantly decreased compared with 2008-10 and was below the WHO-defined threshold for triggering a public health response. National and systematic surveillance is needed to inform Tanzania's public health strategy. KW - HIV KW - adult KW - anti-hiv agents KW - child KW - mothers KW - nucleosides KW - outpatients KW - reverse transcriptase inhibitors KW - tanzania KW - world health organization KW - guidelines KW - public health medicine KW - anti-retroviral agents KW - non-nucleoside reverse transcriptase inhibitors KW - surveillance KW - medical KW - exclusion criteria KW - prevention Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227124 VL - 73 IS - 12 ER -