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

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.

• Authors: Albert Mwafongo, Kondwani Nkanaunena, Yu Zheng, Evelyn Hogg, Wadzanai Samaneka, Lloyd Mulenga, Abraham Siika, Judith Currier, Shahin Lockman, Michael D Hughes, Mina Hosseinipour, AIDS Clinical Trial Group (ACTG) A5208 Team
• Journal: AIDS (London, England) (AIDS) Vol. 28 Issue 8 Pg. 1135-42 (May 15 2014) ISSN: 1473-5571 [Electronic] England
• PMID: 24445367 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• HIV Protease Inhibitors
• Organophosphonates
• RNA, Viral
• Reverse Transcriptase Inhibitors
• Deoxycytidine
• Lopinavir
• Nevirapine
• Tenofovir
• Creatinine
• Emtricitabine
• Adenine
• Ritonavir

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adult
• Antiviral Agents (therapeutic use)
• Creatinine (urine)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Drug Therapy, Combination
• Emtricitabine
• Female
• HIV Infections (drug therapy)
• HIV Protease Inhibitors (administration & dosage, adverse effects)
• HIV-1
• Humans
• Kidney Diseases (chemically induced)
• Lopinavir (therapeutic use)
• Nevirapine (therapeutic use)
• Organophosphonates (therapeutic use)
• RNA, Viral
• Reverse Transcriptase Inhibitors (administration & dosage, adverse effects)
• Ritonavir (therapeutic use)
• Tenofovir
• Treatment Outcome