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  • Open Access

Efficacy and safety of TMC278 in treatment-naïve, HIV-infected patients: week 96 data from TMC278-C204

  • 1,
  • 2,
  • 3,
  • 4,
  • 5,
  • 5 and
  • 6
Journal of the International AIDS Society200811 (Suppl 1) :P2

https://doi.org/10.1186/1758-2652-11-S1-P2

  • Published:

Keywords

  • Sustained Virological Response
  • Efavirenz
  • Virological Response
  • Randomise Phase
  • Sustained Virological Response Rate

Background

NNRTIs are very effective antiretrovirals, but new NNRTIs with improved tolerability are needed.

Methods

A randomised Phase IIb study assessed the investigational next-generation NNRTI, TMC278, 25, 75 and 150 mg QD blinded up to 96 weeks and an open-label control, efavirenz (EFV) 600 mg QD in 368 treatment-naïve patients (33% females). All patients received AZT/3TC (76%) or TDF/FTC (24%).

Summary of results

No differences in efficacy were observed across TMC278 arms or vs. EFV at week 96. The potent antiviral efficacy of TMC278 at week 48 was sustained to week 96. Mean increase from baseline in CD4 cell count was higher at week 96 vs. 48. (Table 1.)

Table 1

  

TMC278

TMC278

TMC278

TMC278

 

Parameter

Wk

25 mg qd (n = 93)

75 mg qd (n = 95)

150 mg qd (n = 91)

All (n = 279)

EFV 600 mg gd (n = 89)1

 

48

80(71–88)

80(72–88)

77(68–86)

79(74–84)

81(73–89)

VL <50 cps/mL (ITT-TLOVR algorithm), % (95% CI)

96

76(68–85)

72(62–81)

71(62–81)

73(68–78)

71(61–80)

Mean (SE) increase from baseline in CD4 cell count, cells/mm3

48

122(12)

145(15)

143(15)

137(8)

127(11)

 

96

146(12)

172(16)

159(16)

159(9)

160(13)

AE incidence at Wk 96 (%)

      

Any AE

 

90

97

92

93

93

AEs leading to discontinuation

 

9

12

14

12

9

Any grade 3 or 4 AEs

 

30

25

26

27

21

Any serious AEs

 

13

14

10

12

15

Grade 3 or 4 lab abnormalities

 

33

22

24

27

24

AEs of interest*

      

Any Rash

 

5

10

13

9‡

21

Nervous system AEs

 

32

32

30

31‡

48

   Headache

 

17

23

19

20

16

   Dizziness

 

13

10

10

11‡

30

   Somnolence

 

3

3

4

11

Psychiatric AEs

 

17

17

14

16

21

   Insomnia

 

8

6

7

7

6

   Depression

 

7

6

3

5

7

   Abnormal dreams/nightmares

 

1

6

0

3

11

Mean (SD) changes from baseline in lipids (mg/dL)

      

   Total cholesterol (TC)

 

10(28)

8(35)

9(29)

9(31)‡

34(31

   LDL-C

 

5(25)

5(30)

3(25)

5(27)‡

18(28)

   HDL-C

 

6(10)

7(11)

6(12)

6(11)‡

11(12)

   Ratio TC/HDL-C

 

-0.4(1.3)

-0.5(1.1)

-0.3(1.0)

-0.4(1.1)

0.1(0.9)

   Triglycerides

 

-8(75)

-15(79)

-7(90)

-10(81)‡

29(87)

1N = 88 for CD4; *Regardless of causality, occurring in ≥ 5% in any group; †well-described AEs for current NNRTIs; §p < 0.05, ‡p < 0.01 vs EFV; Fisher Exact test (AEs); non-parametric Wilcoxon rank-sum test (lipids)

At week 96 vs. week 48, there were few TMC278 dose-related effects, and no change in types nor notable increase in incidence of AEs. All rashes were grade 1 or 2, except one case of grade 3 rash (TMC278 75 mg arm, dapsone-related). Rashes resolved with continued dosing (median duration: all TMC278 17 vs. EFV 15 days). Incidences of grade 3 or 4 nervous system AEs (no discontinuations; all TMC278: 0.7% vs. EFV: 1.1%) and psychiatric AEs (1.8% vs. 1.1%) were low. Psychiatric AEs led to discontinuation in 0.4% vs. 2.2% of patients.

Conclusion

Over 96 weeks, TMC278 demonstrated a high, sustained virological response rate and was generally well tolerated with lower incidences of rash, nervous system and psychiatric AEs, and less lipid increases than EFV.

Authors’ Affiliations

(1)
Department of Infectious Diseases, Saint-Louis Hospital and University of Paris, Paris, France
(2)
Epimed GmbH, Berlin, Germany
(3)
Clinical HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa
(4)
Bumrungrad Hospital Clinical Research Center, Bangkok, Thailand
(5)
Tibotec BVBA, Mechelen, Belgium
(6)
Tibotec Inc., Yardley, PA, USA

Copyright

© Molina et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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