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


CONCLUSIONS
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.
aUniversity of North Carolina Project, Kamuzu Central Hospital, Lilongwe bJohns Hopkins Project, Queen Elizabeth Central Hospital, Blantyre, Malawi cHarvard School of Public Health, Boston, Massachusetts dSocial & Scientific Systems, Inc., Silver Spring, Maryland, USA eUZ-UCSF Collaborative Research Programme, Harare, Zimbabwe fCenter for Infectious Disease Research, Lusaka, Zambia gMoi University (College of Health Sciences), Eldoret, Kenya hUniversity of California, Los Angeles, Los Angeles, California iBrigham and Women's Hospital, Boston, Massachusetts jUniversity of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Albert
A
Mwafongo
Kondwani
K
Nkanaunena
Yu
Y
Zheng
Evelyn
E
Hogg
Wadzanai
W
Samaneka
Lloyd
L
Mulenga
Abraham
A
Siika
Judith
J
Currier
Shahin
S
Lockman
Michael D
MD
Hughes
Mina
M
Hosseinipour
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D003404:Creatinine / Q000652:urine; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015497:HIV-1; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D061466:Lopinavir / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D061466:Lopinavir; D019829:Nevirapine; D000068698:Tenofovir; D003404:Creatinine; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir