Raltegravir for HIV-1 infected children and adolescents: efficacy, safety, and pharmacokinetics

Figures & data

Figure 1 Raltegravir concentration–time curves for the adult formulation (triangles, n = 21) in P1066 cohorts I (≥12 to <19 years) and IIA (≥6 to <12 years) and the chewable tablet formulation (circles, n = 22) in cohorts ii (≥6 to <12 years) and III (≥2 to <6 years).

Table 1 Recommended doses and steady-state pharmacokinetic data for raltegravir in pediatric populationa

Age	Formulation	Patient body weight (kg)	Dose (mg, twice daily)	nb	AUC0–12c (μMxhr)	C12c (nM)
≥12 to <19 years	Film-coated tablet	Regardless of weightd	400	11	15.7 (98%)	333 (78%)
≥6 to <12 years	Film-coated tablet	≥25 kg	400	11	15.8 (120%)	246 (221%)
≥6 to <12 years and ≥2 to <6 yearse	Chewable tablet Chewable tablet	10 to <14 14 to <20 20 to <28 28 to <40 At least 40	75 100 150 200 300	10 12	22.6 (34%) 18.0 (59%)	130 (88%) 71 (55%)
≥6 months to <2 yearsf	Oral granules for suspension			8	20g	115g

Notes:

a From the US Food and Drug Administration;⁴

b number of patients with intensive pharmacokinetic results at the final recommended dose;

c numbers are presented as geometric mean (%CV);

d patients received an approximate dose of 8 mg/kg;

e patients received an approximate dose of 6 mg/kg, maximum dose not to exceed 300 mg, twice daily;

f raltegravir is not approved in this age-group, preliminary data from Spector et al,³¹ patients received an approximate dose of 6 mg/kg twice daily;

g %CV not provided.

Abbreviations: AUC_0–12, area under the curve, 0–12 hours; C₁₂, plasma concentration at 12 hours; CV, coefficient of variation.

Table 2 Efficacy outcome of raltegravir in P1066 subjectsa

Age of patients	≥12 to <19 years	≥6 to <12 years	≥6 to <12 years	≥2 to <6 years	Total (2–18 years)
Cohorts	I	IIA	IIB	III
Number enrolled	59	4	13	20	96
Baseline characteristics
Age (years)b	15 (12–18)	10.5 (8–11)	9 (6–11)	3 (2–5)	13 (2–18)
Male sex (%)	50	75	53.8	35	49
vRNA (log10 copies/mL)c	4.3 (3.1–6)	4.4 (3.5–4.9)	4.3 (3.5–5.2)	4.3 (2.7–5.3)	4.3 (2.7–6)
CD4 cell count (cell/mm^3)b	396.5 (0–872)	806.5 (274–1515)	529 (16–1000)	1086.5 (323–2361)	481 (0–2361)
Prior NNRTI (%)	86.4	75	84.6	50	78.1
Prior Pi (%)	96.6	75	61.5	60	83.3
Week 24 response
% of patients achieving ≥1 log10 HIV RNA decline or <400 copies/mL	72.4%	50%	76.9%	70%	71.6%
% of patients achieving HIV RNA <50 copies/mL	55.2%	50%	53.8%	50%	53.7%
Mean change from baseline in CD4 cell count (cells/mm^3)	114.4	−35.8	143.4	147.2	119.0
Mean change from baseline in CD4 (%)	4.1%	2.2%	0.8%	5.3%	3.8%
Week 48 response
% of patients achieving ≥1 log10 HIV RNA decline or <400 copies/mL	75%	75%	90.9%	84.2%	78.9%
% of patients achieving HIV RNA <50 copies/mL	57.1%	50%	54.5%	57.9%	56.7%
Mean change from baseline in CD4 cell count (cells/mm^3)	168.2	189.5	76.8	158.1	155.7
Mean change from baseline in CD4 (%)	5.2%	6.0%	1.6%	4.3%	4.6%

Notes:

a Data from Nachman et al;³⁰

b,c values presented as median (range).

Abbreviations: NNRTI, non-nucleoside reverse-transcriptase inhibitor; PI, protease inhibitor; HIV, human immunodeficiency virus; vRNA, viral ribonucleic acid; RNA, ribonucleic acid; CD4, cluster of differentiation 4.

Table 3 Comparison between adult (BENCHMRK) study and pediatric efficacy studies of raltegravir

Dose of raltegravir used	Median age of patients, years	Number enrolled	Baseline median plasma HIV-1 RNA copies/mL	Median time of follow-up	% of patients <400 copies/mL	% of patients achieving HIV RNA <50 copies/mL	Reference
400 mg twice daily	45 (41–51)a	462	4.8 (4.1–5.2)a,b	240 weeks	45	42	^Citation8
400 mg twice daily	16 (15–18)a	19	10,000 (4300–83,000)a	80.1 (49.4–96.4) weeksa	21	68	^Citation25
400 mg twice daily	15 (12–17)c	12	5.7 (4.33–6.1)b,c	12 (9–21) monthsc	92	50	^Citation32
6–8 mg/kg/dose twice daily	2–18	96	NA	48 weeks	78.9	56.7	^Citation30

Notes:

a Values in parentheses indicate interquartile range;

b values presented in log10 copies/mL;

c values in parentheses indicate range.

Abbreviations: NA, not available; HIV, human immunodeficiency virus; RNA, ribonucleic acid.

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