Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine.

TitleRenal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine.
Publication TypeJournal Article
Year of Publication2014
AuthorsMwafongo A, Nkanaunena K, Zheng Y, Hogg E, Samaneka W, Mulenga L, Siika A, Currier J, Lockman S, Hughes MD, Hosseinipour M
Corporate AuthorsAIDS Clinical Trial Group(ACTG) A5208 Team
JournalAIDS
Volume28
Issue8
Pagination1135-42
Date Published2014 May 15
ISSN1473-5571
KeywordsAdenine, Adult, Antiviral Agents, Creatinine, Deoxycytidine, Drug Therapy, Combination, Emtricitabine, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Kidney Diseases, Lopinavir, Nevirapine, Organophosphonates, Reverse Transcriptase Inhibitors, Ritonavir, RNA, Viral, Tenofovir, Treatment Outcome
Abstract

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) has been associated with renal insufficiency. Co-administration with boosted protease inhibitors, which increases its exposure, may further increase the risk of renal insufficiency.

METHODS: We compared the incidence of renal events among women taking TDF co-administered with lopinavir/ritonavir (LPV/r) versus those co-administering TDF with nevirapine (NVP). Renal events were defined as a confirmed drop in creatinine clearance associated with a serum creatinine grade 2 or higher, or that leading to treatment modification.

RESULTS: Overall, 741 HIV-infected women were enrolled into the study. Of these, 24 (3.2%) had reportable renal events (18 in LPV/r arm, six in NVP arm). In multivariate analysis, renal events were significantly associated with the LPV/r arm [odds ratio (OR) 3.12, 95% confidence interval (CI) 1.21, 8.05; P = 0.019], baseline HIV-1 RNA (OR 2.65, 95% CI 1.23, 5.69 per 1 log10 copies/ml higher; P = 0.013) and baseline creatinine clearance (OR 0.83, 95% CI 0.70-0.98 per 10 ml/min higher; P = 0.030). In multivariate analysis evaluating renal events requiring treatment modification, only baseline HIV-1 RNA and creatinine clearance were significantly associated (OR 4.41, 95% CI 1.65, 11.78 per 1 log10 copies/ml higher; P = 0.003 and OR 0.80, 95% CI 0.64, 0.99 per 10 ml/min higher; P = 0.040, respectively).

CONCLUSION: The rates of renal events were relatively low in the two treatment arms. However, patients taking TDF co-administered with LPV/r had significantly more renal events compared to those co-administered with NVP. Furthermore, higher baseline HIV RNA and lower creatinine clearance were associated with the development of renal insufficiency requiring treatment modification.

DOI10.1097/QAD.0000000000000202
Alternate JournalAIDS
PubMed ID24445367
PubMed Central IDPMC4176616
Grant ListAI38838 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
K24 AI056933 / AI / NIAID NIH HHS / United States
K24 AI56933 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI108568 / AI / NIAID NIH HHS / United States