Transition from BID to QD: clinical data
Whetham J.
Switching from NVP BID to NVP QD after risk period may be safe.
110/284 NVP pts switch from BID to NVP QD.
Liver function tests at and since switch to QD were reviewed; viral control remained <40 cp/ml.
Switching to NVP OD after the high risk period for adverse events results in no increased toxicity.
High CD4 count at switch did not seem to be associated with a high rate of adverse events.
(Whetham J, et al., BHIVA 2006, Poster P11)
Bruggeman R.
The aim of this study was to determine if switching from NVP BID to QD has any hepatotoxic consequences. Twenty nine patients (3 females) took NVP BID for 6 months and achieved VLs <50 cp/mL. All patients had normal liver function test (LFT) values.
Fourteen patients were randomised to switch to NVP QD. LFTs, CD4 cell count, VL and NVP serum levels were monitored at 1, 3 and 6 months.
Viral control was maintained in both groups. There was no difference in ALT levels between the groups – indicating that there was no increase in hepatotoxicity due to switching to NVP QD.
(Bruggeman, R et al., ICAAC 2007, Chicago. Abs. A-1407)
Benzie A.
Prospective, single centre, cohort study that enrolled all ARV naïve patients starting NVP BID plus 3TC or FTC and 1 NRTI between January 2002 and January 2006 at St Mary’s Hospital, London.
The total number of patients eligible for the analysis was 173. At Week 48, 85% of NVP patients had VL <50 cp/mL. Mean CD4 cell count had increased by 204 cells/mm3.
Twenty three subjects (13%) had switched to NVP QD by Week 48. The total number of patients who switched by Year 5 was 49.
No increased rates of hepatotoxicity (increased ALT levels) were observed in patients who switched to NVP QD.
No significant differences in total or HDL cholesterol levels or in CD4 cell count or NRTI background were detected over the first 12 months of switching to NVP QD.
No patients taking NVP QD experienced treatment failure.
In this cohort, switching to NVP QD within the first year of HAART was associated with high treatment success rates, irrespective of the NRTI backbone.
(Benzie A, et. al., 11th EACS 2007, Madrid, Sp. Abs P7.9/02)
NODy study
This study compared the efficacy, hepatotoxicity and other safety parameters in HIV-1 infected patients who switched from NVP BID to NVP QD. It was a randomized, open label, multi centre, 12 month, Spanish study. A total of 298 patients were evaluable: 143 in the NVP QD arm; and 146 in the NVP BID arm.
Virological success rates were similar in both arms (K-M estimate, ITT, p=0.673). The time to Grade 3-4 hepatotoxicity was similar in both arms (K-M estimate, ITT, p=0.273). Co-infection with hepatitis C (HCV+) and increased ALT levels at baseline were independently associated with hepatotoxicity in this study.
Switching to NVP QD was associated with low frequency of hepatotoxicity and maintenance of viral suppression.
(Podzamczer, D, et al. 15th Conference on Retroviruses and Opportunistic Infections. 2008. Boston, USA. Abs 960)
ATHENA & Swiss SHCS
Data from 5244 patients in the ATHENA and Swiss SHCS cohorts who had taken NVP were included in the intent to treat (ITT) analysis. The majority of patients (85.2%) took NVP BID, while 12.2% had switched from BID to NVP QD and 12.0% had initiated NVP with QD dosing.
Patients who had discontinued NVP because of HSRs (rash and/or hepatotoxicity) within 18 weeks of starting NVP were identified. The median follow up was 4.6 years (2.4-6.7).
HSRs occurred in 301/5244 (5.7%) of patients taking NVP for the first time. Stratification by dosing schedule showed:
NVP BID: 201/4471 (4.5%)
NVP QD: 41/629 (6.5%)
During lead in dose: 59/144 (41.0%)
Hepatotoxicity occurred at similar rates in both QD (1.11%) and BID (1.12%) patients. Discontinuation of NVP due to rash was more common in QD (5.4%) than in BID (3.47%, p=0.016) patients. In multivariate analysis, the dosing schedule remained significant (OR 1.69, p=0.008).
A total of 641 patients switched from BID to NVP QD. Only 3/641 (0.47%) discontinued due to HSR (2 rashes, 1 hepatotoxicity).
The ATHENA and Swiss Cohort Investigators concluded that it was safe to switch a stable NVP-based combination therapy from BID to QD.
(Calmy A, et. al., 11th EACS 2007, Madrid, Sp. Abs PS5/3)
Parts of this CME:
start of the CME
Clinical pharmacology of NVP
Pharmacokinetics
2NN: efficacy
Other clinical sudies on NVP QD efficacy
The future
Conclusions