Safety and efficacy of once-daily nevirapine dosing: a multicohort study.
BACKGROUND
Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy.


METHODS
Patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort study, Canadian HAART Observational Medical Evaluation and Research (HOMER) cohort and Swiss HIV Cohort Study (SHCS) using NVP-based combination therapy either once daily or twice daily were included. Risk factors for discontinuing NVP because of hypersensitivity reactions (HSRs) were investigated using multivariate logistic regression. Risk factors for virological failure 96 weeks after NVP initiation were identified using logistic regression and Cox models.


RESULTS
Of 5,636 patients (774 once daily and 4,862 twice daily), 268 (4.8%) discontinued NVP because of HSR between 2 and 18 weeks. Logistic regression showed that, compared with patients with detectable HIV type-1 (HIV-1) RNA starting twice-daily NVP, there was a significantly higher risk of discontinuation of once-daily NVP because of HSR in patients with detectable HIV-1 RNA at the start of NVP (odds ratio [OR] 1.52; P=0.04), whereas the risk was actually significantly lower in patients starting once-daily NVP with undetectable HIV-1 RNA (OR 0.44; P=0.04). Cox models showed that risk of virological failure was not different for twice- versus once-daily NVP in treatment-naive patients (twice-daily versus once-daily hazard ratio [HR] 1.01; P=0.95), treatment-experienced patients experiencing treatment failure (twice-daily versus once-daily HR 1.22; P=0.30) or patients with undetectable HIV-1 RNA simplifying treatment with NVP (twice-daily versus once-daily HR 1.29; P=0.30).


CONCLUSIONS
Initiation of a once-daily NVP-based regimen in patients with suppressed viraemia carries a low risk of treatment-limiting HSR. Once- or twice-daily NVP-based regimens appear to have similar antiretroviral efficacy.
Calmy
Alexandra
A
Division of Infectious Disease/HIV unit, University Hospital Geneva, Geneva, Switzerland. acalmy@gmail.com
Vallier
Nathalie
N
Nguyen
Alain
A
Lange
Joep Ma
JM
Battegay
Manuel
M
de Wolf
Frank
F
Reiss
Peter
P
Lima
Viviane D
VD
Hirschel
Bernard
B
Hogg
Robert S
RS
Yip
Benita
B
Montaner
Julio S G
JS
Wit
Ferdinand W
FW
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D063065:Organophosphonates; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine