eprintid: 10086053 rev_number: 23 eprint_status: archive userid: 608 dir: disk0/10/08/60/53 datestamp: 2019-11-20 12:28:53 lastmod: 2021-12-06 00:05:59 status_changed: 2019-11-20 12:28:53 type: article metadata_visibility: show creators_name: Ross, LL creators_name: Walker, AS creators_name: Lou, Y creators_name: Tenorio, AR creators_name: Gibb, DM creators_name: Double, J creators_name: Gilks, C creators_name: McCoig, CC creators_name: Munderi, P creators_name: Musoro, G creators_name: Kityo, CM creators_name: Grosskurth, H creators_name: Hakim, J creators_name: Mugyenyi, PN creators_name: Cutrell, A creators_name: Perger, T creators_name: Shaefer, MS title: Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30–49 vs ≥50 mL/min ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 keywords: Antiretroviral therapy, Creatinine, Hematology, Renal system, Adverse events, Toxicity, HIV, Zimbabwe note: © 2019 Ross et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). abstract: A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine dosing in patients with impaired creatinine clearance (CLcr). Safety data collected through 96 weeks were analyzed after stratification by baseline CLcr (estimated using Cockcroft-Gault) of 30–49 mL/min (n = 168) versus ≥50 mL/min (n = 3,132) and treatment regimen. The Grade 3–4 adverse events (AEs) and serious AEs (for hematological, hepatic and gastrointestinal events), maximal toxicities for liver enzymes, serum creatinine and bilirubin and maximum treatment-emergent hematology toxicities were comparable for groups with baseline CLcr 30–49 versus CLcr≥50 mL/min. No new risks or trends were identified from this dataset. Substantial and similar increases in the mean creatinine clearance (>25 mL/min) were observed from baseline though Week 96 among participants who entered the trial with CLcr 30–49 mL/min, while no increase or smaller median changes in creatinine clearance (<7 mL/min) were observed for participants who entered the trial with CLcr ≥50 mL/min. Substantial increases (> 150 cells/ mm3) in mean CD4+ cells counts from baseline to Week 96 were also observed for participants who entered the trial with CLcr 30–49 mL/min and those with baseline CLcr ≥50 mL/min. Though these results are descriptive, they suggest that HIV-positive patients with CLcr of 30–49 mL/min would have similar AE risks in comparison to patients with CLcr ≥50 mL/min when initiating antiretroviral therapy delivering doses of 300 mg of lamivudine daily through 96 weeks of treatment. Overall improvements in CLcr were observed for patients with baseline CLcr 30–49 mL/min. date: 2019-11-14 publisher: Public Library of Science (PLoS) official_url: https://doi.org/10.1371/journal.pone.0225199 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1719546 doi: 10.1371/journal.pone.0225199 lyricists_name: Gibb, Diana lyricists_name: Walker, Ann lyricists_id: MGIBB48 lyricists_id: ASWAL40 actors_name: Gibb, Diana actors_id: MGIBB48 actors_role: owner full_text_status: public publication: PLoS One volume: 14 number: 11 article_number: e0225199 citation: Ross, LL; Walker, AS; Lou, Y; Tenorio, AR; Gibb, DM; Double, J; Gilks, C; ... Shaefer, MS; + view all <#> Ross, LL; Walker, AS; Lou, Y; Tenorio, AR; Gibb, DM; Double, J; Gilks, C; McCoig, CC; Munderi, P; Musoro, G; Kityo, CM; Grosskurth, H; Hakim, J; Mugyenyi, PN; Cutrell, A; Perger, T; Shaefer, MS; - view fewer <#> (2019) Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30–49 vs ≥50 mL/min. PLoS One , 14 (11) , Article e0225199. 10.1371/journal.pone.0225199 <https://doi.org/10.1371/journal.pone.0225199>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10086053/1/Ross%202019%20PLOS%20One%20DART%20changes%20in%20CLcr%20over%20time.pdf