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Predictors of Response to TPV/r in Pediatric Patients: Results of PACTG1051/BI1182.14
Juan C Salazar*1,2, Juan C Salazar*1,2, P Cahn3, M Della Negra4, G Castelli-Gattinara5, C Fortuny6, P Flynn1,7, P Flynn1,7, R Yogev1,8, R Yogev1,8, P Ruan1,9, P Ruan1,9, J Mikl10, and A Jelaska10
1PACTG 1051 Study Team; 2Connecticut Children's Med Ctr, Hartford, US; 3Fndn Huesped, Buenos Aires, Argentina; 4Inst de Infectologia Emilio Ribas, Sao Paulo, Brazil; 5Bambino Gesu Children's Hosp, Rome, Italy; 6Hosp St Joan de Deu, Barcelona, Spain; 7St Jude Children's Res Hosp, Memphis, TN, US; 8Children's Memorial Hosp, Northwestern Univ Med Sch, Chicago, IL, US; 9Statistical & Data Analysis Ctr, Harvard Sch of Publ Hlth, Boston, MA, US; and 10Boehringer Ingelheim Pharma, Ridgefield, CT, US
Background: Many antiretroviral experienced,
HIV-positive children have genotypic evidence of resistance to currently
available ARV therapy. New options are needed for this population. Tipranavir (TPV) is a new generation protease
inhibitor (PI) active against multi-PI resistant HIV. This analysis sought to
define the predictors of response to TPV-based regimens in children.
Methods: 115 children (2-18 years) were randomized to
low dose (LD) TPV/r (n = 58, 290/115 mg/m2) or high dose (HD) TPV/r
(n = 57, 375/150 mg/m2) plus optimized background regimen.
Multivariate logistic regression (LR) analysis was performed to determine the
predictors of Week 48 virological outcomes.
Results: Baseline mean viral load (VL): 4.7 log10
copies/mL; mean CD4 (CD4%): 492 cells/mm3 (20%); median previous
ARVs: 6; genotypic resistance to all PIs: 49.6%. Most common background
regimen: 2 NRTI; enfuvirtide use: 13%. At Week 48 (NCF), 39.7% (34.5%) of LD
patients and 45.6% (35.1%) of HD patients achieved VL <400 (<50)
copies/mL. 6% of patients developed Grade 3 ALT elevations. Logistic regression
(LR) modelling was implemented to investigate the associations between a number of factors
and achieving VL<400 copies/mL
at week 48. The factors considered were treatment group; genotypic inhibitory quotient (GIQ); baseline
VL; age group; TPV adherence (defined as % of visits when TPV adherence was
95-120%); and genotypic sensitivity
score (GSS). The LR results are
summarized in the following table.
LR results for VL <400 copies/mL at
Week 48:
|
Factor
|
Odds Ratio (95% C.I.)
|
p value
|
|
TPV/r LD vs HD
|
1.34 (0.49, 3.65)
|
0.57
|
|
GIQ
Q2 vs Q1
Q3 vs Q1
Q4 vs Q1
|
12.35 (2.03, 75.01)
17.08 (2.87, 101.62)
38.37 (5.14, 286.27)
|
0.006
0.002
< 0.001
|
|
Baseline VL (copies/mL)
<1K vs
>10K-100K
>1K-10K vs
>10K-100K
>100K vs
>10K-100K
|
0.21 (0.01, 5.75)
1.94 (0.46, 8.13)
0.30 (0.09, 0.94)
|
0.355
0.367
0.038
|
|
Age group (yrs)
2-<6 vs 12-18
6-<12 vs 12-18
|
2.59 (0.71, 9.39)
0.61 (0.19, 1.97)
|
0.148
0.412
|
|
Adherence
Per 10%
improvement
|
1.23 (1.04, 1.46)
|
0.014
|
|
Genotypic Sensitivity Score
0.25-1 vs 0
1.25-2.25 vs 0
|
1.46 (0.49, 4.39)
0.33 (0.08, 1.33)
|
0.500
0.120
|
Conclusions: TPV/r regimens are well tolerated
and effective in ARV experienced children. Higher GIQ values and better
adherence were associated with achieving a VL <400
copies/mL at 48 weeks of
treatment with TPV/r.
|
