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Efficacy and safety of TMC278 in treatment-naïve, HIV-1-infected patients with HBV/HCV co-infection enrolled in the phase III ECHO and THRIVE trials

  • 1,
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Journal of the International AIDS Society201013 (Suppl 4) :P210

https://doi.org/10.1186/1758-2652-13-S4-P210

  • Published:

Keywords

  • Nevirapine
  • Virologic Response
  • Virologic Response Rate
  • Hepatic Safety
  • High Virologic Response

Introduction

TMC278 had a high virologic response rate, non-inferior to EFV, in two Phase III double-blind trials ECHO (TMC278-C209, NCT00540449) and THRIVE (TMC278-C215, NCT00543725) in treatment-naïve HIV-infected adult patients. As the use of NNRTIs, particularly nevirapine, has been associated with hepatic-related adverse events (AEs), especially in HIV/hepatitis B (HBV) and/or hepatitis C (HCV) co-infected patients, a subgroup analysis of these events was performed on the pooled Week 48 Phase III data.

Methods

Patients (N=1368) with alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) ≤ 5x upper limit of normal received TMC278 25mg qd or EFV 600mg qd, plus TDF/FTC (ECHO) or TDF/FTC, AZT/3TC or ABC/3TC (THRIVE). HIV/HBV and/or HCV co-infection status was determined at baseline in 1335 patients by HBV surface antigen, HCV antibody and RNA testing.

Results

At baseline, 112/1335 patients (8.4%) had evidence of HIV/HBV and/or HCV co-infection (randomised to TMC278, n=49: 7.3%; EFV, n=63: 9.5%). Table 1 summarises the outcomes.

Compared with HIV mono-infected patients, co-infected patients had more hepatic AEs (clinical and laboratory) and lower virologic responses, which were similar across treatment groups. Hepatic AEs rarely led to treatment discontinuation (TMC278: n=3 vs. EFV: n=9 patients). There were no fatal hepatic AEs.

Table 1

 

HIV/HBV and/or HCV co-infected patients

 

HIV mono-infected patients

 
 

TMC278 25mg qd

EFV 600mg qd

TMC278 25mg qd

EFV 600mg qd

Efficacy (Week 48 outcomes)*

N=49

N=63

N=621

N=602

% (95% CI) with viral load <50 copies/mL, ITT-TLOVR

73.5 (60.7-86.3)

79.4 (69.1-89.6)

85.0 (82.2-87.8)

82.6 (79.5-85.6)

Mean CD4 count (95% CI)

N=48

N=63

N=621

N=602

Baseline, cells/mm3

230 (198-263)

246 (216-276)

262 (251-273)

274 (262-285)

Change from baseline, NC=F, cells/mm3

+137 (100-175)

+192 (147-238)

+197 (186-209)

+173 (161-185)

Change from baseline, NC=F, %

+6.6 (5.0-8.3)

+7.7 (6.4-9.0)

+8.6 (8.1-9.0)

+8.4 (7.9-8.8)

Safety , §

    

Treatment-emergent hepatic AEs of interest, n (%)

N=54

N=66

N=632

N=616

Any hepatic AE

15 (27.8)

17 (25.8)

23 (3.6)

28 (4.5)

Hepatobiliary disorders¶

3 (5.6)

7 (10.6)

6 (0.9)

9 (1.5)

HBV or HCV reported as an AE

3 (5.6)

5 (7.6)

-

-

Hepatic laboratory abnormalities reported as an AE

9 (16.7)

8 (12.1)

19 (3.0)

21 (3.4)

Grade 3 to 4 hepatic laboratory abnormalities, n (%)

N=54

N=66

N=631

N=604

ALT increased

9 (16.7)

11 (16.7)

1 (0.2)

12 (2.0)

AST increased

7 (13.0)

5 (7.6)

7 (1.1)

14 (2.3)

Hyperbilirubinaemia

0

0

4 (0.6)

1 (0.2)

ITT-TLOVR = intent-to-treat-time-to-loss of virologic response; CI=confidence interval; *Patients included in efficacy analysis were those with baseline HBV/HCV assessments; †NC=F = non completer = failure: missing values after discontinuation imputed with change = 0; Last observation carried forward otherwise; ‡Safety analyses performed using all available data, including beyond Week 48; §Patients who seroconverted for HBV/HCV during the study were included in the subgroup of HIV/HBV and/or HCV co-infected patients; ¶Selection of preferred terms from System Organ Class as defined by MedDRA. Compared with HIV mono-infected patients, co-infected patients had more hepatic AEs (clinical and laboratory) and lower virologic responses, which were similar across treatment groups. Hepatic AEs rarely led to treatment discontinuation (TMC278: n=3 vs. EFV: n=9 patients). There were no fatal hepatic AEs.

Conclusions

Overall, both TMC278 and EFV were well tolerated with no hepatic safety differences observed. Hepatic AEs were more common in co-infected than in HIV mono-infected patients (27% vs. 4%, respectively), but there were no differences between the two treatment groups. Virologic responses were similar for TMC278 and EFV within the co-infected and HIV mono-infected groups, and lower in co-infected than in HIV mono-infected patients.

Authors’ Affiliations

(1)
Chelsea and Westminster Hospital, London, UK
(2)
Centro Médico Puerta de Hierro, Zapopan, Jal, Mexico
(3)
Saint-Pierre University Hospital, Brussels, Belgium
(4)
Centro Médico São Francisco, Curitiba, Brazil
(5)
University of Miami, Miami, FL, USA
(6)
Clinique Medicale du Quartier Latin, Montreal, Canada
(7)
Beijing PUMC Hospital, Beijing, China
(8)
University of Pennsylvania, Philadelphia, PA, USA
(9)
Tibotec BVBA, Beerse, Belgium
(10)
Tibotec Inc., Titusville, NJ, USA

Copyright

© Nelson et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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