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  • Open Access

Efficacy and safety by baseline HIV-RNA and CD4 count in treatment-naive patients treated With atazanavir/r and lopinavir/r in the CASTLE study

  • 1,
  • 2,
  • 2,
  • 2,
  • 1,
  • 1 and
  • 2
Journal of the International AIDS Society200811 (Suppl 1) :P8

https://doi.org/10.1186/1758-2652-11-S1-P8

  • Published:

Keywords

  • Virologic Response
  • Lower Response Rate
  • Count Stratum
  • Castle Study

Purpose of the study

In the CASTLE study, lower response rates were observed in patients with baseline HIV-RNA ≥100,000 copies/mL in both arms and were associated with lower baseline CD4 cell count for LPV/r but not ATV/r.

Methods

Randomized, open-label, prospective study comparing once-daily ATV/r with twice-daily LPV/r, both with fixed-dose TDF/FTC in 883 treatment-naive patients. Treatment outcomes of HIV-RNA <50 c/mL at week 48 using confirmed virologic response (CVR) and grade 2–4 treatment-related AEs through week 48 are presented by pre-specified baseline HIV-RNA and CD4 cell count strata.

Summary of results

The proportion of responders (CVR HIV-RNA <50 c/mL, ITT) at week 48 by baseline HIV RNA strata (<100,000, 100,000–<500,000, and ≥500,000) were 83%, 76%, and 64% for ATV/r and 80%, 74%, and 61% for LPV/r (Table 1).
Table 1

CVR Treatment Outcomes of HIV RNA <50 c/mL at Week 48 by Baseline CD4 Cell Count, n (%).

 

ATV/r

   

LPV/r

   

As-Randomized

<50

50–<100

100–<200

≥200

<50

50–<100

100–<200

≥200

ITT

n = 58

n = 45

n = 106

n = 222

n = 48

n = 29

n = 134

n = 228

Responder

45 (78)

34 (76)

80 (75)

178 (80)

30 (63)

20 (69)

104 (78)

182 (80)

Virologic failure*

7 (12)

7 (16)

17 (16)

26 (12)

6 (13)

7 (24)

13 (10)

24 (11)

Discontinued

6 (10)

4 (9)

9 (8)

16 (7)

12 (25)

2 (7)

16 (12)

20 (9)

On-treatment, n/N (%)

45/52 (87)

34/40 (85)

80/95 (84)

178/202 (88)

30/35 (86)

20/25 (80)

104/114 (91)

182/201 (91)

*Includes never suppressed and on study through week 48, discontinued due to insufficient viral load response through week 48, and rebound without resuppression.

In patients with both baseline CD4 <100 and HIV-RNA ≥100,000, 60/83 (72%) on ATV/r and 40/64 (63%) on LPV/r achieved HIV RNA <50 c/mL (CVR, ITT). Incidence of grades 2–4 treatment-related AEs through week 48 by baseline HIV-RNA strata (<100,000, 100,000–<500,000, and ≥500,000) were 29%, 26%, and 15% for ATV/r; and 31%, 27%, and 30% for LPV/r. (Table 2.)
Table 2

Grade 2–4 Treatment-Related AEs through Week 48 by Baseline CD4 Cell Count (cells/mm3), n (%).

 

ATV/r

   

LPV/r

   

As-treated

<50

50–<100

100–<200

≥200

<50

50–<100

100–<200

≥200

 

n = 59

n = 45

n = 106

n = 222

n = 47

n = 29

n = 133

n = 224

Any

12 (20)

9 (20)

22 (21)

71 (32)

19 (40)

7 (24)

35 (26)

65 (29)

Jaundice

1 (2)

0

2 (2)

12 (5)

0

0

0

0

Diarrhea

0

1 (2)

3 (3)

6 (3)

8 (17)

3 (10)

12 (9)

26 (12)

Nausea

2 (3)

0

6 (6)

9 (4)

5 (11)

2 (7)

9 (7)

16 (7)

Conclusion

Lower response rates at higher baseline HIV-RNA were seen for both ATV/r and LPV/r. The trend for lower response rates at lower baseline CD4 cell counts for LPV/r observed in the ITT analysis did not appear to be present in the on-treatment analysis. ATV/r and LPV/r had consistent adverse event (AE) profiles within each arm by baseline HIV-RNA. More AEs, most commonly diarrhea and nausea, were observed with LPV/r at low baseline CD4 cell counts.

Authors’ Affiliations

(1)
Bristol-Myers Squibb Research and Development, Plainsboro, NJ, USA
(2)
Bristol-Myers Squibb Research and Development, Wallingford, CT, USA

Copyright

© Uy et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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