A Phase 1/2 interventional study of Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC) in HIV Infections, sponsored by Bristol-Myers Squibb. Completed at 17 sites in 6 countries. Open to participants aged 3 Months to 6 Years. Per ClinicalTrials.gov, last updated 2014-04-29.
Sponsored by Bristol-Myers Squibb · Phase 1/2, Interventional, and Treatment
The primary purpose of this study is to find the dose of Efavirenz for young children. The safety and how the medication is tolerated will also be studied.
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EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m\^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m\^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m\^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m\^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
Drug: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC)
Drug pages: Efavirenz · Didanosine · Emtricitabine
Oral Solution, Capsules or Tablets, Oral, once daily Efavirenz (EFV) per weight-based dosing nomogram (max 720 mg) Didanosine (ddI) 240 mg/m2 (max 400 mg) Emtricitabine (FTC) 6 mg/kg (max 200 mg) Where EFV oral solution is commercially available: 48 weeks or until 3rd birthday (whichever is longer); Where EFV oral solution NOT commercially available: until 7th birthday or until able to swallow EFV capsules (whichever occurs first)
Also known as: Sustiva, BMS-561525
Maximum Observed Plasma Concentration (Cmax) and Plasma Concentration 24 Hours Post-dose (Cmin) of EFV at Week 2 - Pharmacokinetic Evaluable Population
Cmax and Cmin were derived from plasma concentrations versus time using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.
Time frame: Week 2
Area Under the Plasma Concentration Time Curve (AUC) Over One Dosing Interval From Time Zero to 24 Hours Post-dose(TAU) at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was \< LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in micromolars\*time (µM•h).
Time frame: Week 2
Apparent Oral Clearance (CLT/F) of EFV at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations of EFV were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F was calculated by dividing the dose of EFV by AUC(TAU) of EFV. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).
Time frame: Week 2
Apparent Oral Clearance Adjusted for Body Weight (CLT/F/kg) of EFV at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations of EFV were determined using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).
Time frame: Week 2
The Number of Participants With Plasma HIV RNA < 400 Copies Per Milliliter (c/mL) at Week 48 as Analyzed by Different Algorithms - All Treated Participants
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 400 c/mL at Week 48; participants were failures if virologic rebound occurred at or before Week 48; therapy discontinued before Week 48; no response by Week 48, or missing HIV RNA at Week 48 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 400 c/mL closest to the planned Week 48 visit and within the predefined Week 48 visit window; those on treatment and missing their Week 48 measurement were responders only if previous and subsequent measurements to the Week 48 visit window were \< 400 c/mL; denominator was all who remained on treatment through Week 48. Snapshot: participants were responders according to the last on-treatment HIV RNA \< 400 c/mL in the predefined Week 48 visit window; denominator was all treated participants.
Time frame: Week 48
The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 48 as Analyzed by Different Algorithms - All Treated Participants
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 50 c/mL at Week 48; participants were failures if virologic rebound occurred at or before Week 48; therapy discontinued before Week 48; no response by Week 48, or missing HIV RNA at Week 48 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 50 c/mL closest to the planned Week 48 visit and within the predefined Week 48 visit window; those on treatment and missing their Week 48 measurement were responders only if previous and subsequent measurements to the Week 48 visit window were \< 50 c/mL; denominator was all who remained on treatment through Week 48. Snapshot: participants were responders according to the last on-treatment HIV RNA \< 50 c/mL in the predefined Week 48 visit window; denominator was all treated participants.
Time frame: Week 48
The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 400 c/mL at Week 24; participants were failures if virologic rebound occurred at or before Week 24; therapy discontinued before Week 24; no response by Week 24, or missing HIV RNA at Week 24 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 400 c/mL closest to the planned Week 24 visit and within the predefined Week 24 visit window; those on treatment and missing their Week 24 measurement were responders only if previous and subsequent measurements to the Week 24 visit window were \< 400 c/mL; denominator was all who remained on treatment through Week 24.
Time frame: Week 24
The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 50 c/mL at Week 24; participants were failures if virologic rebound occurred at or before Week 24; therapy discontinued before Week 24; no response by Week 24, or missing HIV RNA at Week 24 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 50 c/mL closest to the planned Week 24 visit and within the predefined Week 24 visit window; those on treatment and missing their Week 24 measurement were responders only if previous and subsequent measurements to the Week 24 visit window were \< 50 c/mL; denominator was all who remained on treatment through Week 24.
Time frame: Week 24
Log10 c/mL HIV RNA Changes From Baseline Through Week 48 - Treated Participants
HIV RNA measured as log10 copies per milliliter (c/mL) plasma. HIV RNA values ≥ 1,000 c/mL were considered evidence of infection. A decrease in number of c/mL is an improvement for the participant. HIV RNA was first measured using the ultrasensitive and standard Roche Amplicor PCR, version 1.5, and then the method of measurement was switched to the COBAS AmpliPrep/COBAS TaqMan HIV IVD method. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline through Week 48
CD4 Cell Count Change From Baseline at Weeks 24 and 48 - Treated Participants
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeters to the third power (cells/mm\^3). An increase from baseline in the number of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline to Weeks 24 and 48
Percent of CD4 Cells Change From Baseline at Weeks 24 and 48 - Treated Participants
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeter to the third power (cells/mm\^3). Percent of CD4 cells is the number of CD4 cells per total number of cells measured\*100. An increase in the percent of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline to Weeks 24 and 48
Number of Participants With On-Treatment Adverse Events (AEs), Related Adverse Events, Serious Adverse Events (SAEs), Death, Discontinuation Due to Adverse Events, and CDC Class C AIDS Events
Center for Disease Control and Prevention (CDC) classification of Class C events used to define acquired immunodeficiency syndrome (AIDS): include pneumocystis pneumonia, pneumonia, pulmonary tuberculosis. AE=new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. AE Severity: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling (Division of AIDs Table, published December 2004). Baseline=within 50 days post screening, prior to start of study drug. 2 categories for death presented (on-treatment and enrolled/not treated).
Time frame: Baseline to Week 96
Number of Participants With Liver Function Test Laboratory Abnormalities - Treated Population
Abnormalities were determined from laboratory measurements analyzed at the central or local laboratory. Division of AIDS Table (DAIDS) for Grading Severity of Adult and Pediatric AEs version (v) Dec 2004. Upper limit of normal (ULN): lower limit of normal (LLN), alanine transaminase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). ALT Grade (Gr) 1: 1.25 to 2.5\*ULN; Gr 2: 2.6 to 5.0\*ULN; Gr 3: 5.1 to 10.0\*ULN; Gr 4: \>10.0\*ULN. AST Gr 1: 1.25 to 2.5\*ULN; Gr 2: 2.6 to 5.0\*ULN; Gr 3: 5.1 to 10.0\*ULN; Gr 4: \>10.0\*ULN. Total bilirubin Gr 1: 1.25 to 1.5\*ULN; Gr 2: 1.6 to 2.5\*ULN; Gr 3: 2.6 to 5.0\*ULN; Gr 4: \>5.0\*ULN. ALP (U/L) Gr 1: 1.25 to 2.5\*ULN, Gr 2: 2.6 to 5.0\*ULN, Gr 3: 5.1 to 10.0\*ULN, Gr 4: \>10.0\*ULN. Albumin (low) Gr 1: 3 grams per deciliter (g/dL) to \<LLN ; Gr 2: 2.0-2.9 g/dL; Gr 3: \< 2 g/dL. Gr 4: Not applicable. Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline to Week 96
Number of Participants With Lipid and Glucose Laboratory Abnormalities - Treated Participants
Abnormalities were determined from measurements analyzed at central or local laboratory. DAIDS Grading Severity of Adult and Pediatric AEs v Dec 2004. Total Cholesterol (fasting) Gr 1: 170 - 199 mg/dL; Gr 2: 200 - 300 mg/dL; Gr 3 \>300 mg/dL; Gr 4 Not Applicable(NA). LDL cholesterol, fasting: Gr 1: 110-129 mg/dL; Gr 2: 130-189 mg/dL; Gr 3 \>=190 mg/dL; Gr 4 NA. Triglycerides, fasting: Gr 1: NA; Gr 2 500-750 mg/dL; Gr 3: 751-1,200 mg/dL; Gr 4: \>1,200 mg/dL. Glucose, serum, high, fasting and (non-fasting): Gr 1: 110 - 125 (116-160) mg/dL; Gr 2: 126-250 (161- 250) mg/dL; Gr 3: 251-500 (251-500) mg/dL; Gr 4: \>500 (\> 500) mg/dL. Glucose, serum, low, \>=1 month of age (\<1 month): Gr 1: 55-64 (50-54) mg/dL; Gr 2: 40-54 (40-49) mg/dL; Gr 3: 30-39 (30-39) mg/dL; Gr 4: \<30 (\<30) mg/dL. Baseline: within 50 days after the screening visit and was prior to start of study medication (Week 1). Only those in 4th arm were old enough to fast prior to testing; other arms did not have fasting samples taken.
Time frame: Baseline to Week 96
Number of Participants With Serum Chemistry Abnormalities - Treated Participants
Central/local laboratory. DAIDS v 2004. Bicarbonate, low: Gr 1: 16 milliequivalents per liter (mEq/L) - \< LLN; Gr 2: 11.0-15.9 mEq/L; Gr 3: 8.0-10.9 mEq/L; Gr 4: \<8.0 mEq/L; calcium, high Gr 1: 10.6-11.5 mg/dL; Gr 2: 11.6-12.5 mg/dL; Gr 3 12.6-13.5 mg/dL; Gr 4: \>13.5 mg/dL; calcium, low Gr1: 7.8-8.4 mg/dL; Gr2: 7.0-7.7 mg/dL; Gr3: 6.1-6.9 mg/dL; Gr 4: \<6.1 mg/dL; creatinine Gr1: 1.1-1.3\*ULN; Gr 2: 1.4-1.8\*ULN; Gr 3: 1.9-3.4\*ULN; Gr 4: \>=3.5\*ULN; lipase Gr 1: 1.1-1.5\*ULN; Gr 2: 1.6-3.0\*ULN; Gr 3: 3.1-5.0\*ULN; Gr 4: \>5.0\*ULN; potassium high (low) Gr 1: 5.6-6.0 (3.0-3.4) mEq/L; Gr 2: 6.1-6.5 (2.5-2.9) mEq/L; Gr 3: 6.6-7.0 (2.0-2.4) mEq/L; Gr 4: \>7.0 (\<2.0) mEq/L; sodium, high (low) Gr 1: 146-150 (130-135) mEq/L; Gr 2: 151-154 (125-129) mEq/L; Gr 3: 155-159 (121-124) mEq/L; Gr 4: \>=160 (\<=120) mEq/L; uric acid Gr 1: 7.5-10.0 mg/dL; Gr 2: 10.1-12.0 mg/dL; Gr 3: 12.1-15.0 mg/dL; Gr 4: \>15.0 mg/dL. Baseline within 50 days post screening, prior to start of study medication.
Time frame: Baseline to Week 96
Number of Participants With Hematologic Abnormalities - Treated Participants
Abnormalities were determined from laboratory measurements analyzed at the central or local laboratory. DAIDS DAIDS Grading Severity of Adult and Pediatric AEs v Dec 2004. Hemoglobin Gr 1: 8.5-10.0 g/dL; Gr 2: 7.5-8.4 g/dL; Gr 3: 6.50-7.4 g/dL; Gr 4: \<6.5 g/dL; Platelets, decreased: Gr 1: 100.000-124.999\*10\^9/L; Gr 2: 50.000-99.999\*10\^9/L; Gr 3: 25.000-49.999\*10\^9/L; Gr 4: \<25.000\*10\^9/L; White blood cell count (WBC) decreased Gr 1: 2.000-2.500\*10\^9/L; Gr 2: 1.500-1.999\*10\^9/L; Gr 3: 1.000-1.499\*10\^9/L; Gr 4: \<1.000\*10\^9/L. Baseline visit was within 50 days post screening and was prior to start of study drug (Week 1).
Time frame: Baseline to Week 96
Number of Treated Participants With Resistance Associated Genotypic and Phenotypic Changes in Viruses - Participants With Virologic Failure, Lack of Suppression or Viral Load Rebound
At baseline, treatment-naïve screened by genotype; treatment-experienced screened by genotype and phenotype. Genotypic resistance: presence of substitutions in reverse transcriptase (RT) gene and/or presence of mutations that confer resistance to nucleoside reverse transcriptase inhibitor class. Phenotype resistance: FTC: \> 3.1\* the 50% inhibitory concentration (IC50) of the control strain; EFV: \> 3.3\* IC50 ; ddI: \> 2.6\*IC50. Virologic failure: \<1 log10 decrease in HIV RNA from Week 16 on; confirmatory HIV RNA within 14-35 days; HIV RNA \> 10,000 c/mL with prior value \< 400 c/mL; confirmatory HIV RNA 14-35 days. Monogram Biosciences Phenosense™ assay ( EFV and FTC: biologic cutoffs=3 and 3.5, respectively; ddI: clinical cutoff: lower limit=1.39; upper limit = 2.2.); VircoTYPE™ HIV-1 v 4.3.01( EFV, FTC: biologic cutoffs=3.3 and 3.1, respectively;ddI: clinical cutoff: lower limit = 0.9; upper limit = 2.6. No genotypic/phenotypic changes in presence of virologic failure=no resistance.
Time frame: Baseline to Week 48
Number of Participants With Acquisition of Resistance to EFV Categorized by AUC Relationship - Evaluable Pharmacokinetic Population
PK parameters were evaluated 2 weeks post start of dosing. Based on observed AUC, measured in micromoles (μM)\*h, dosing was increased, remained the same, or decreased at next visit to achieve the desired AUC (110-380 μM\*h). Number of participants who became resistant was categorized by those who required additional dosing after Week 2 (AUC\<110 μM\*h) and those who did not. AUC: derived from plasma concentration of EFV versus time. Plasma concentrations for determination of AUC were obtained using a validated LC-MS/MS method. LLOQ for EFV = 10.0 ng/mL and ULOQ = 8,000 ng/mL. AUC calculated by log- and linear trapezoidal summations. Genotypic resistance=presence of substitutions in the RT gene and/or presence of mutations that confer resistance to entire nucleoside reverse transcriptase inhibitor class. Phenotypic resistance=EFV: \> 3.3\* IC50 of control strain. Assays: Monogram Biosciences Phenosense™ GT (EFV biologic cutoff=3) and VircoTYPE™ HIV-1 v 4.3.01( EFV biologic cutoff=3.3).
Time frame: Baseline to Week 48
Cmax and Cmin of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
Cmax and Cmin were derived from plasma concentration versus time. Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. All reportable Cmin values were \<LLOQ in all age groups except \>=6 months to \< 2 years (Group 2); LLOQ/2 was imputed for those summary statistics;in Group 2, 9 of 10 Cmin values were \<LLOQ; LLOQ/2 was imputed for those samples for summary statistics. The lower limit of quantification (LLOQ) for ddI was 2.50 nanograms per milliliter (ng/mL). Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.
Time frame: Week 2
AUC (TAU) of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations were obtained using a validated LC-MS/MS at Week 2. The lower limit of quantification (LLOQ) for ddI was 2.50 nanograms per milliliter (ng/mL). AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was \< LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in nanograms\*time per milliliter (ng•h/mL).
Time frame: Week 2
CLT/F of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). CLT/F was calculated by dividing the dose of ddI by AUC(TAU) of ddI. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).
Time frame: Week 2
CLT/F/kg of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).
Time frame: Week 2
Terminal Phase Elimination Half-life (T-HALF) in Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population
Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the T-HALF was summarized using a mean. Terminal elimination plasma half-life=ln2 divided by K where K is the absolute value of the slope of the terminal phase of the plasma profile as determined by log-linear regression of at least three data points. T-HALF was measured in hours (h).
Time frame: Week 2
The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants
Virologic Response - Observed Cases (VR-OC): participants were responders at a specific week according to a single on-treatment HIV RNA \< 400 c/mL closest to the planned visit and within the predefined visit window; those on treatment and missing their specific week measurement were responders only if previous and subsequent measurements to that week visit window were \< 400 c/mL; denominator was all who remained on treatment through the specific week.
Time frame: Weeks 60, 72, 84, and 96
The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants
Virologic Response - Observed Cases (VR-OC): participants were responders at a specific week according to a single on-treatment HIV RNA \< 50 c/mL closest to the planned visit and within the predefined visit window; those on treatment and missing their specific week measurement were responders only if previous and subsequent measurements to that week visit window were \< 50 c/mL; denominator was all who remained on treatment through the specific week.
Time frame: Weeks 60, 72, 84, and 96
Log10 c/mL HIV RNA Changes From Baseline at Weeks 60, 72, 84 and 96 - Treated Participants
HIV RNA measured as log10 copies per milliliter (c/mL) plasma. HIV RNA values ≥ 1,000 c/mL were considered evidence of infection. A decrease in number of c/mL is an improvement for the participant. HIV RNA was first measured using the ultrasensitive and standard Roche Amplicor PCR, version 1.5, and then the method of measurement was switched to the COBAS AmpliPrep/COBAS TaqMan HIV IVD method. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline through Weeks 60, 72, 84, and 96
CD4 Cell Count Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeters to the third power (cells/mm\^3). An increase from baseline in the number of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline to Weeks 60, 72, 84, and 96
Percent of CD4 Cells Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeter to the third power (cells/mm\^3). Percent of CD4 cells is the number of CD4 cells per total number of cells measured\*100. An increase in the percent of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
Time frame: Baseline to Weeks 60, 72, 84, and 96
This study initiated February 2007 and completed July 2013. All participants enrolled in countries where efavirenz (EFV) oral solution was not commercially available could remain on study until their 7th birthday or until they were able to swallow EFV capsules (whichever occurred first).
| Milestone | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Started | 15 | 10 | 4 | 8 |
| Completed | 7 | 5 | 0 | 5 |
| Not completed | 8 | 5 | 4 | 3 |
| Withdrew: Adverse event | 2 | 0 | 0 | 0 |
| Withdrew: Death | 1 | 0 | 1 | 0 |
| Withdrew: Lack of efficacy | 3 | 3 | 1 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 | 2 | 0 |
| Withdrew: Poor or non-compliance | 1 | 1 | 0 | 1 |
| Withdrew: No longer meets criteria | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 |
Cmax and Cmin were derived from plasma concentrations versus time using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.
| ng/mL | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Cmax | 3790 ± 76 | 1998 ± 51 | 2167 ± 68 | 2632 ± 83 |
| Cmin | 391 ± 141 | 445 ± 57 | 648 ± 75 | 1185 ± 111 |
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 400 c/mL at Week 48; participants were failures if virologic rebound occurred at or before Week 48; therapy discontinued before Week 48; no response by Week 48, or missing HIV RNA at Week 48 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 400 c/mL closest to the planned Week 48 visit and within the predefined Week 48 visit window; those on treatment and missing their Week 48 measurement were responders only if previous and subsequent measurements to the Week 48 visit window were \< 400 c/mL; denominator was all who remained on treatment through Week 48. Snapshot: participants were responders according to the last on-treatment HIV RNA \< 400 c/mL in the predefined Week 48 visit window; denominator was all treated participants.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total Participants |
|---|---|---|---|---|---|
| CVR (NC=F) n=15, 10, 4, 8, 37 | 7 | 6 | 3 | 5 | 21 |
| VR-OC n=9, 9, 3, 6, 27 | 7 | 6 | 3 | 5 | 21 |
| SNAPSHOT n=15, 10, 4, 8, 37 | 7 | 6 | 3 | 5 | 21 |
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 50 c/mL at Week 48; participants were failures if virologic rebound occurred at or before Week 48; therapy discontinued before Week 48; no response by Week 48, or missing HIV RNA at Week 48 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 50 c/mL closest to the planned Week 48 visit and within the predefined Week 48 visit window; those on treatment and missing their Week 48 measurement were responders only if previous and subsequent measurements to the Week 48 visit window were \< 50 c/mL; denominator was all who remained on treatment through Week 48. Snapshot: participants were responders according to the last on-treatment HIV RNA \< 50 c/mL in the predefined Week 48 visit window; denominator was all treated participants.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| CVR (NC=F) n=15, 10, 4, 8, 37 | 6 | 6 | 2 | 4 | 18 |
| VR-OC n=9, 9, 3, 6, 27 | 6 | 5 | 2 | 4 | 17 |
| SNAPSHOT n=15, 10, 4, 8, 37 | 6 | 5 | 2 | 4 | 17 |
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 400 c/mL at Week 24; participants were failures if virologic rebound occurred at or before Week 24; therapy discontinued before Week 24; no response by Week 24, or missing HIV RNA at Week 24 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 400 c/mL closest to the planned Week 24 visit and within the predefined Week 24 visit window; those on treatment and missing their Week 24 measurement were responders only if previous and subsequent measurements to the Week 24 visit window were \< 400 c/mL; denominator was all who remained on treatment through Week 24.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| CVR (n=15, 10, 4, 8, 37) | 8 | 7 | 4 | 7 | 26 |
| VR-OC(n=11,10 ,4, 7, 32) | 8 | 7 | 4 | 6 | 25 |
Algorithms: Confirmed Virologic Response (CVR) non-completer = failure (NC = F): participants were responders if they achieved confirmed HIV RNA \< 50 c/mL at Week 24; participants were failures if virologic rebound occurred at or before Week 24; therapy discontinued before Week 24; no response by Week 24, or missing HIV RNA at Week 24 and beyond. Virologic Response - Observed Cases (VR-OC): participants were responders according to a single on-treatment HIV RNA \< 50 c/mL closest to the planned Week 24 visit and within the predefined Week 24 visit window; those on treatment and missing their Week 24 measurement were responders only if previous and subsequent measurements to the Week 24 visit window were \< 50 c/mL; denominator was all who remained on treatment through Week 24.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| CVR (n=15, 10, 4, 8, 37) | 4 | 4 | 3 | 4 | 15 |
| VR-OC (n=11, 10, 4, 7, 32) | 5 | 5 | 2 | 4 | 16 |
HIV RNA measured as log10 copies per milliliter (c/mL) plasma. HIV RNA values ≥ 1,000 c/mL were considered evidence of infection. A decrease in number of c/mL is an improvement for the participant. HIV RNA was first measured using the ultrasensitive and standard Roche Amplicor PCR, version 1.5, and then the method of measurement was switched to the COBAS AmpliPrep/COBAS TaqMan HIV IVD method. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| log10 c/mL | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Baseline (n=13,10,4,7,34) | 5.88 (5.12 to 5.92) | 5.88 (5.32 to 5.88) | 5.88 (5.38 to 5.88) | 5.50 (4.64 to 5.88) | 5.88 (4.97 to 5.88) |
| Week 2 (n=12, 9, 4, 5, 30) | -1.89 ± 0.270 | -2.26 ± 0.278 | -2.42 ± 0.496 | -1.93 ± 0.277 | -2.11 ± 0.162 |
| Week 4 (n=11, 8, 4, 6, 29) | -2.18 ± 0.372 | -2.49 ± 0.308 | -2.86 ± 0.160 | -3.04 ± 0.343 | -2.63 ± 0.195 |
| Week 8 (n=11, 10, 3, 7, 31) | -2.73 ± 0.412 | -2.91 ± 0.366 | -2.92 ± 0.070 | -3.27 ± 0.338 | -2.92 ± 0.209 |
| Week 12 (n=10, 10, 3, 6, 29) | -2.48 ± 0.541 | -3.19 ± 0.431 | -4.02 ± 0.310 | -3.31 ± 0.362 | -3.14 ± 0.261 |
| Week 16 (n=10, 10, 4, 7, 31) | -2.72 ± 0.527 | -3.17 ± 0.496 | -4.11 ± 0.240 | -3.44 ± 0.326 | -3.27 ± 0.253 |
| Week 24 (n=10, 9, 3, 7, 29) | -3.46 ± 0.610 | -3.92 ± 0.525 | -4.18 ± 0.585 | -2.95 ± 0.372 | -3.28 ± 0.278 |
| Week 32 (n=9, 9, 4, 6, 28) | -2.75 ± 0.547 | -3.28 ± 0.506 | -3.73 ± 0.276 | -2.93 ± 0.461 | -3.27 ± 0.259 |
| Week 40 (n=7, 9, 4 ,6, 26) | -4.01 ± 0.434 | -4.17 ± 0.435 | -4.02 ± 0.236 | -2.93 ± 0.620 | -3.93 ± 0.240 |
| Week 48 (n=9, 9, 3, 6, 27) | -2.92 ± 0.551 | -3.27 ± 0.469 | -3.27 ± 0.320 | -2.93 ± 0.622 | -3.18 ± 0.271 |
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeters to the third power (cells/mm\^3). An increase from baseline in the number of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| cells/mm^3 | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Baseline (n=10, 9, 3, 6, 28) | 1518 (829 to 2202) | 1569 (1149 to 2284) | 517 (129 to 558) | 413 (23 to 688) | 1144 (529 to 1930) |
| Week 24 (n=6, 7, 3, 6, 22) | 259 ± 410.8 | 82 ± 330 | 31 ± 818.3 | 283 ± 195.2 | 177 ± 185.3 |
| Week 48 (n=7, 8, 2, 5, 22) | -258 ± 401.5 | 346 ± 381.8 | 971 ± 956.0 | 284 ± 296.8 | 196 ± 220.8 |
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeter to the third power (cells/mm\^3). Percent of CD4 cells is the number of CD4 cells per total number of cells measured\*100. An increase in the percent of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| percentage of CD4 cells | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Baseline (n=7, 9, 3, 5, 24) | 28 (17 to 40) | 26 (25 to 28) | 12 (5 to 20) | 7 (2 to 23) | 24 (14 to 28) |
| Week 24 (n=3, 7, 3, 5, 18) | 14 ± 12.0 | 2 ± 2.8 | 9 ± 3.2 | 10 ± 4.2 | 9 ± 2.3 |
| Week 48 (n=5, 8, 2, 5, 20) | 5 ± 4.5 | 4 ± 3.5 | 8 ± 8.9 | 11 ± 2.9 | 6 ± 2.1 |
Plasma concentrations were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was \< LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in micromolars\*time (µM•h).
| µM•h | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Area Under the Plasma Concentration Time Curve (AUC) Over One Dosing Interval From Time Zero to 24 Hours Post-dose(TAU) at Week 2 - Pharmacokinetic Evaluable Population | 129.5 ± 98 | 71.4 ± 49 | 93.8 ± 68 | 130.8 ± 98 |
Plasma concentrations of EFV were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F was calculated by dividing the dose of EFV by AUC(TAU) of EFV. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).
| L/h | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Apparent Oral Clearance (CLT/F) of EFV at Week 2 - Pharmacokinetic Evaluable Population | 9.54 ± 63 | 19.69 ± 85 | 13.16 ± 58 | 9.11 ± 73 |
Plasma concentrations of EFV were determined using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).
| L/h/kg | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Apparent Oral Clearance Adjusted for Body Weight (CLT/F/kg) of EFV at Week 2 - Pharmacokinetic Evaluable Population | 2.07 ± 71 | 2.36 ± 84 | 1.44 ± 51 | 0.66 ± 72 |
Center for Disease Control and Prevention (CDC) classification of Class C events used to define acquired immunodeficiency syndrome (AIDS): include pneumocystis pneumonia, pneumonia, pulmonary tuberculosis. AE=new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. AE Severity: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling (Division of AIDs Table, published December 2004). Baseline=within 50 days post screening, prior to start of study drug. 2 categories for death presented (on-treatment and enrolled/not treated).
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Death (Treated Participants) | 1 | 0 | 1 | 0 | 2 |
| Deaths (Enrolled Participants, Not treated) | 2 | 0 | 0 | 0 | 2 |
| SAE (Treated Participants) | 8 | 5 | 4 | 3 | 20 |
| AE (All Grades,Treated Participants) | 13 | 9 | 4 | 6 | 32 |
| Grade 2 - 4 AEs (Treated Participants) | 11 | 7 | 4 | 5 | 27 |
| Grade 3 - 4 AEs (Treated Participants) | 4 | 2 | 3 | 1 | 10 |
| Related AE (All Grades,Treated Participants) | 8 | 5 | 4 | 4 | 21 |
| Discontinued due to AE (Treated Participants) | 2 | 0 | 0 | 0 | 2 |
| CDC Class C AIDS event (Treated Participants) | 1 | 1 | 0 | 0 | 2 |
Abnormalities were determined from laboratory measurements analyzed at the central or local laboratory. Division of AIDS Table (DAIDS) for Grading Severity of Adult and Pediatric AEs version (v) Dec 2004. Upper limit of normal (ULN): lower limit of normal (LLN), alanine transaminase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). ALT Grade (Gr) 1: 1.25 to 2.5\*ULN; Gr 2: 2.6 to 5.0\*ULN; Gr 3: 5.1 to 10.0\*ULN; Gr 4: \>10.0\*ULN. AST Gr 1: 1.25 to 2.5\*ULN; Gr 2: 2.6 to 5.0\*ULN; Gr 3: 5.1 to 10.0\*ULN; Gr 4: \>10.0\*ULN. Total bilirubin Gr 1: 1.25 to 1.5\*ULN; Gr 2: 1.6 to 2.5\*ULN; Gr 3: 2.6 to 5.0\*ULN; Gr 4: \>5.0\*ULN. ALP (U/L) Gr 1: 1.25 to 2.5\*ULN, Gr 2: 2.6 to 5.0\*ULN, Gr 3: 5.1 to 10.0\*ULN, Gr 4: \>10.0\*ULN. Albumin (low) Gr 1: 3 grams per deciliter (g/dL) to \<LLN ; Gr 2: 2.0-2.9 g/dL; Gr 3: \< 2 g/dL. Gr 4: Not applicable. Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Albumin (n=12, 10, 4, 7, 33) | 0 | 0 | 1 | 0 | 1 |
| ALP (n=12, 10, 4, 7, 33) | 8 | 2 | 2 | 5 | 17 |
| ALT (n=12, 10, 4, 7, 33) | 7 | 3 | 2 | 0 | 12 |
| AST (n=12, 10, 4, 7, 33) | 8 | 1 | 1 | 0 | 10 |
Abnormalities were determined from measurements analyzed at central or local laboratory. DAIDS Grading Severity of Adult and Pediatric AEs v Dec 2004. Total Cholesterol (fasting) Gr 1: 170 - 199 mg/dL; Gr 2: 200 - 300 mg/dL; Gr 3 \>300 mg/dL; Gr 4 Not Applicable(NA). LDL cholesterol, fasting: Gr 1: 110-129 mg/dL; Gr 2: 130-189 mg/dL; Gr 3 \>=190 mg/dL; Gr 4 NA. Triglycerides, fasting: Gr 1: NA; Gr 2 500-750 mg/dL; Gr 3: 751-1,200 mg/dL; Gr 4: \>1,200 mg/dL. Glucose, serum, high, fasting and (non-fasting): Gr 1: 110 - 125 (116-160) mg/dL; Gr 2: 126-250 (161- 250) mg/dL; Gr 3: 251-500 (251-500) mg/dL; Gr 4: \>500 (\> 500) mg/dL. Glucose, serum, low, \>=1 month of age (\<1 month): Gr 1: 55-64 (50-54) mg/dL; Gr 2: 40-54 (40-49) mg/dL; Gr 3: 30-39 (30-39) mg/dL; Gr 4: \<30 (\<30) mg/dL. Baseline: within 50 days after the screening visit and was prior to start of study medication (Week 1). Only those in 4th arm were old enough to fast prior to testing; other arms did not have fasting samples taken.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Total Cholesterol (n=9,10,4,0,23) | 2 | 4 | 1 | NA | 7 |
| Total Cholesterol Fasting (n=0,0,0,7,7) | NA | NA | NA | 1 | 1 |
| Glucose High (n=11,10,3,0,24) | 1 | 0 | 0 | NA | 1 |
| Glucose Low (n=11,10,3,0,24) | 2 | 1 | 0 | NA | 3 |
| Glucose High Fasting (n=0,0,0,7,7) | NA | NA | NA | 1 | 1 |
| LDL cholesterol (n=9,10,4,0,23) | 0 | 4 | 0 | NA | 4 |
| LDL cholesterol fasting (n=0,0,0,7,7) | NA | NA | NA | 1 | 1 |
Central/local laboratory. DAIDS v 2004. Bicarbonate, low: Gr 1: 16 milliequivalents per liter (mEq/L) - \< LLN; Gr 2: 11.0-15.9 mEq/L; Gr 3: 8.0-10.9 mEq/L; Gr 4: \<8.0 mEq/L; calcium, high Gr 1: 10.6-11.5 mg/dL; Gr 2: 11.6-12.5 mg/dL; Gr 3 12.6-13.5 mg/dL; Gr 4: \>13.5 mg/dL; calcium, low Gr1: 7.8-8.4 mg/dL; Gr2: 7.0-7.7 mg/dL; Gr3: 6.1-6.9 mg/dL; Gr 4: \<6.1 mg/dL; creatinine Gr1: 1.1-1.3\*ULN; Gr 2: 1.4-1.8\*ULN; Gr 3: 1.9-3.4\*ULN; Gr 4: \>=3.5\*ULN; lipase Gr 1: 1.1-1.5\*ULN; Gr 2: 1.6-3.0\*ULN; Gr 3: 3.1-5.0\*ULN; Gr 4: \>5.0\*ULN; potassium high (low) Gr 1: 5.6-6.0 (3.0-3.4) mEq/L; Gr 2: 6.1-6.5 (2.5-2.9) mEq/L; Gr 3: 6.6-7.0 (2.0-2.4) mEq/L; Gr 4: \>7.0 (\<2.0) mEq/L; sodium, high (low) Gr 1: 146-150 (130-135) mEq/L; Gr 2: 151-154 (125-129) mEq/L; Gr 3: 155-159 (121-124) mEq/L; Gr 4: \>=160 (\<=120) mEq/L; uric acid Gr 1: 7.5-10.0 mg/dL; Gr 2: 10.1-12.0 mg/dL; Gr 3: 12.1-15.0 mg/dL; Gr 4: \>15.0 mg/dL. Baseline within 50 days post screening, prior to start of study medication.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Bicarbonate, low (n=12, 10, 4, 7, 33) | 10 | 9 | 4 | 5 | 28 |
| Sodium, low (n=12, 10, 4, 7, 33) | 5 | 4 | 2 | 4 | 15 |
| Sodium High (n=12, 10, 4, 7, 33) | 1 | 1 | 0 | 1 | 3 |
| Uric Acid (n=12, 10, 4, 7, 33) | 0 | 1 | 1 | 0 | 2 |
| Calcium High (n= 12, 10, 4, 7, 33) | 0 | 2 | 0 | 1 | 3 |
| Calcium Low (n= 12, 10, 4, 7, 33) | 0 | 4 | 1 | 1 | 6 |
| Potassium High (n= 12, 10, 4, 7, 33) | 5 | 4 | 0 | 0 | 9 |
| Potassium Low (n= 12, 10, 4, 7, 33) | 1 | 0 | 1 | 1 | 3 |
| Lipase Total (n= 12, 10, 4, 7, 33) | 1 | 0 | 0 | 2 | 3 |
Abnormalities were determined from laboratory measurements analyzed at the central or local laboratory. DAIDS DAIDS Grading Severity of Adult and Pediatric AEs v Dec 2004. Hemoglobin Gr 1: 8.5-10.0 g/dL; Gr 2: 7.5-8.4 g/dL; Gr 3: 6.50-7.4 g/dL; Gr 4: \<6.5 g/dL; Platelets, decreased: Gr 1: 100.000-124.999\*10\^9/L; Gr 2: 50.000-99.999\*10\^9/L; Gr 3: 25.000-49.999\*10\^9/L; Gr 4: \<25.000\*10\^9/L; White blood cell count (WBC) decreased Gr 1: 2.000-2.500\*10\^9/L; Gr 2: 1.500-1.999\*10\^9/L; Gr 3: 1.000-1.499\*10\^9/L; Gr 4: \<1.000\*10\^9/L. Baseline visit was within 50 days post screening and was prior to start of study drug (Week 1).
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Hemoglobin (n=11, 10, 4, 7, 32) | 4 | 5 | 2 | 1 | 12 |
| Platelet (n=11, 10, 4, 7, 32) | 1 | 1 | 0 | 0 | 2 |
| Neutrophils (n=11, 10, 4, 7, 32) | 7 | 2 | 0 | 1 | 10 |
At baseline, treatment-naïve screened by genotype; treatment-experienced screened by genotype and phenotype. Genotypic resistance: presence of substitutions in reverse transcriptase (RT) gene and/or presence of mutations that confer resistance to nucleoside reverse transcriptase inhibitor class. Phenotype resistance: FTC: \> 3.1\* the 50% inhibitory concentration (IC50) of the control strain; EFV: \> 3.3\* IC50 ; ddI: \> 2.6\*IC50. Virologic failure: \<1 log10 decrease in HIV RNA from Week 16 on; confirmatory HIV RNA within 14-35 days; HIV RNA \> 10,000 c/mL with prior value \< 400 c/mL; confirmatory HIV RNA 14-35 days. Monogram Biosciences Phenosense™ assay ( EFV and FTC: biologic cutoffs=3 and 3.5, respectively; ddI: clinical cutoff: lower limit=1.39; upper limit = 2.2.); VircoTYPE™ HIV-1 v 4.3.01( EFV, FTC: biologic cutoffs=3.3 and 3.1, respectively;ddI: clinical cutoff: lower limit = 0.9; upper limit = 2.6. No genotypic/phenotypic changes in presence of virologic failure=no resistance.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Lack of suppression with Changes (PP) | 2 | 1 | 0 | 0 | 3 |
| Viral Load Rebound with Changes(PP) | 1 | 1 | 0 | 0 | 2 |
| Viral Failure with Changes (outside 35 day limit) | 0 | 3 | 1 | 1 | 5 |
PK parameters were evaluated 2 weeks post start of dosing. Based on observed AUC, measured in micromoles (μM)\*h, dosing was increased, remained the same, or decreased at next visit to achieve the desired AUC (110-380 μM\*h). Number of participants who became resistant was categorized by those who required additional dosing after Week 2 (AUC\<110 μM\*h) and those who did not. AUC: derived from plasma concentration of EFV versus time. Plasma concentrations for determination of AUC were obtained using a validated LC-MS/MS method. LLOQ for EFV = 10.0 ng/mL and ULOQ = 8,000 ng/mL. AUC calculated by log- and linear trapezoidal summations. Genotypic resistance=presence of substitutions in the RT gene and/or presence of mutations that confer resistance to entire nucleoside reverse transcriptase inhibitor class. Phenotypic resistance=EFV: \> 3.3\* IC50 of control strain. Assays: Monogram Biosciences Phenosense™ GT (EFV biologic cutoff=3) and VircoTYPE™ HIV-1 v 4.3.01( EFV biologic cutoff=3.3).
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Resistant; AUC<110 µM•h(n=2,7,2,3,14) | 1 | 3 | 1 | 1 | 6 |
| Resistant; AUC>=110 µM•h(n=10,3,2,4,19) | 2 | 2 | 0 | 0 | 4 |
Cmax and Cmin were derived from plasma concentration versus time. Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. All reportable Cmin values were \<LLOQ in all age groups except \>=6 months to \< 2 years (Group 2); LLOQ/2 was imputed for those summary statistics;in Group 2, 9 of 10 Cmin values were \<LLOQ; LLOQ/2 was imputed for those samples for summary statistics. The lower limit of quantification (LLOQ) for ddI was 2.50 nanograms per milliliter (ng/mL). Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.
| ng/mL | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Cmax (n=12, 10, 4, 6) | 850 ± 48 | 1193 ± 39 | 356 ± 69 | 376 ± 93 |
| Cmin (n=4, 10, 4, 3) | 1.25 ± 0 | 1.54 ± 132 | 1.25 ± 0 | 1.25 ± 0 |
Plasma concentrations were obtained using a validated LC-MS/MS at Week 2. The lower limit of quantification (LLOQ) for ddI was 2.50 nanograms per milliliter (ng/mL). AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was \< LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in nanograms\*time per milliliter (ng•h/mL).
| ng•h/mL | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| AUC (TAU) of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population | 1445 ± 76 | 2848 ± 53 | 1038 ± 54 | 1000 ± 41 |
Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). CLT/F was calculated by dividing the dose of ddI by AUC(TAU) of ddI. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).
| L/h | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| CLT/F of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population | 40.7 ± 110 | 35.6 ± 42 | 113.9 ± 111 | 143.0 ± 53 |
Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).
| L/h/kg | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| CLT/F/kg of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population | 7.88 ± 85 | 4.26 ± 30 | 11.36 ± 116 | 10.34 ± 70 |
Plasma concentrations for ddI were determined using a validated LC/MS/MS assay. The LLOQ for ddI was 2.50 nanograms per milliliter (ng/mL). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the T-HALF was summarized using a mean. Terminal elimination plasma half-life=ln2 divided by K where K is the absolute value of the slope of the terminal phase of the plasma profile as determined by log-linear regression of at least three data points. T-HALF was measured in hours (h).
| h | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years |
|---|---|---|---|---|
| Terminal Phase Elimination Half-life (T-HALF) in Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population | 0.92 ± 0.1374 | 1.41 ± 0.859 | 1.73 ± 1.007 | 1.14 ± 0.214 |
Virologic Response - Observed Cases (VR-OC): participants were responders at a specific week according to a single on-treatment HIV RNA \< 400 c/mL closest to the planned visit and within the predefined visit window; those on treatment and missing their specific week measurement were responders only if previous and subsequent measurements to that week visit window were \< 400 c/mL; denominator was all who remained on treatment through the specific week.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Week 60 (n=7, 8, 3, 4, 22) | 7 | 6 | 2 | 4 | 19 |
| Week 72 (n=7, 7, 2, 4, 20) | 7 | 5 | 1 | 4 | 17 |
| Week 84 (n=7, 7, 2, 4, 20) | 7 | 5 | 1 | 4 | 17 |
| Week 96 (n=7, 6, 2, 4, 19) | 7 | 5 | 1 | 4 | 17 |
Virologic Response - Observed Cases (VR-OC): participants were responders at a specific week according to a single on-treatment HIV RNA \< 50 c/mL closest to the planned visit and within the predefined visit window; those on treatment and missing their specific week measurement were responders only if previous and subsequent measurements to that week visit window were \< 50 c/mL; denominator was all who remained on treatment through the specific week.
| participants | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Week 60 (n=7, 8, 3, 4, 22) | 4 | 5 | 2 | 3 | 14 |
| Week 72 (n=7, 7, 2, 4, 20) | 7 | 5 | 1 | 4 | 17 |
| Week 84 (n=7, 7, 2, 4, 20) | 7 | 5 | 1 | 3 | 16 |
| Week 96 (n=7, 6, 2, 4, 19) | 6 | 5 | 0 | 4 | 15 |
HIV RNA measured as log10 copies per milliliter (c/mL) plasma. HIV RNA values ≥ 1,000 c/mL were considered evidence of infection. A decrease in number of c/mL is an improvement for the participant. HIV RNA was first measured using the ultrasensitive and standard Roche Amplicor PCR, version 1.5, and then the method of measurement was switched to the COBAS AmpliPrep/COBAS TaqMan HIV IVD method. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| log10 c/mL | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Baseline (n=13,10,4,7,34) | 5.88 (5.12 to 5.92) | 5.88 (5.32 to 5.88) | 5.88 (5.38 to 5.88) | 5.50 (4.64 to 5.88) | 5.88 (4.97 to 5.88) |
| Week 60 (n=7, 8, 3, 4, 22) | -3.92 ± 0.458 | -3.44 ± 0.539 | -3.26 ± 0.322 | -3.48 ± 0.575 | -3.50 ± 0.259 |
| Week 72 (n=7, 6, 1, 3, 17) | -4.08 ± 0.438 | -2.75 ± 0.603 | -3.20 ± NA | -4.18 ± 0.410 | -3.45 ± 0.290 |
| Week 84 (n=7, 7, 2, 4, 20) | -4.08 ± 0.438 | -3.28 ± 0.563 | -2.18 ± 1.022 | -3.51 ± 0.583 | -3.37 ± 0.283 |
| Week 96 (n=7, 6, 2, 4, 19) | -3.82 ± 0.423 | -3.73 ± 0.686 | -2.15 ± 0.848 | -3.57 ± 0.597 | -3.45 ± 0.296 |
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeters to the third power (cells/mm\^3). An increase from baseline in the number of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| cells/mm^3 | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Baseline (n=10,9,3,6,28) | 1518 (829 to 2202) | 1569 (1149 to 2284) | 517 (129 to 558) | 413 (23 to 688) | 1144 (529 to 1930) |
| Week 60 (n=6, 6, 2,3,17) | -870 (-1331 to -315) | -914 (-1509 to 725) | 580 (-11 to 1171) | 676 (506 to 887) | -315 (-1331 to 676) |
| Week 72 (n=5, 7, 1, 3, 16) | -1178 (-1422 to -588) | 234 (-1540 to 624) | -50 (-50 to -50) | 620 (619 to 811) | 92 (-1300 to 620) |
| Week 84 (n=6, 7, 1, 3, 17) | -937 (-1331 to -155) | 59 (-1416 to 316) | 101 (101 to 101) | 497 (339 to 722) | 59 (-1304 to 334) |
| Week 96 (n=6, 6, 1, 3, 16) | -834 (-1437 to -176) | -43 (-1291 to 222) | 402 (402 to 402) | 744 (295 to 1243) | -40 (-1185 to 314) |
A CD4 cell is an antigenic marker of helper/inducer T cells. These cells were counted during the hematology cell counts performed during a Complete Blood Cell count (CBC) performed by the Central Laboratory. CD4 are measured as number of cells per millimeter to the third power (cells/mm\^3). Percent of CD4 cells is the number of CD4 cells per total number of cells measured\*100. An increase in the percent of CD4 cells is an improvement. The Baseline visit was within 50 days after the screening visit and was prior to start of study medication (Week 1).
| percentage of CD4 cells | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | EFV+ddI+FTC in All Participants |
|---|---|---|---|---|---|
| Baseline (n=7,9,3,5,24) | 28 (17 to 40) | 26 (25 to 28) | 12 (5 to 20) | 7 (2 to 23) | 24 (14 to 28) |
| Week 60 (n=3,6,2,3,14) | 10 (-9 to 13) | 3 (-5 to 5) | 7 (-1 to 15) | 13 (9 to 26) | 7 (-1 to 13) |
| Week 72 (n=2,7,1,3,13) | -14 (-17 to -10) | 1 (-5 to 13) | -1 (-1 to -1) | 12 (11 to 26) | 1 (-5 to 12) |
| Week 84 (n=3,7,1,3,14) | -3 (-22 to 21) | 8 (0 to 11) | 2 (2 to 2) | 12 (5 to 34) | 7 (0 to 12) |
| Week 96 (n=3,6,1,3,13) | -2 (-19 to 6) | 7 (3 to 10) | 15 (15 to 15) | 14 (14 to 28) | 7 (3 to 14) |
Collected over 96 Weeks (Last patient, last visit).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| EFV+ddI+FTC in All Participants | — | 20/37 (54.1%) | 30/37 (81.1%) |
| Event | EFV+ddI+FTC in All Participants |
|---|---|
| PneumoniaInfections and infestations | 8/37 |
| GastroenteritisInfections and infestations | 3/37 |
| VaricellaInfections and infestations | 2/37 |
| EczemaSkin and subcutaneous tissue disorders | 1/37 |
| Oral herpesInfections and infestations | 1/37 |
| Bacterial infectionInfections and infestations | 1/37 |
| BronchiolitisInfections and infestations | 1/37 |
| EpilepsyNervous system disorders | 1/37 |
| Appendicitis perforatedInfections and infestations | 1/37 |
| Bovine tuberculosisInfections and infestations | 1/37 |
| Event | EFV+ddI+FTC in All Participants |
|---|---|
| DiarrhoeaGastrointestinal disorders | 19/37 |
| NasopharyngitisInfections and infestations | 13/37 |
| PharyngitisInfections and infestations | 10/37 |
| Upper respiratory tract infectionInfections and infestations | 10/37 |
| PyrexiaGeneral disorders | 9/37 |
| VomitingGastrointestinal disorders | 7/37 |
| Blood alkaline phosphatase increasedInvestigations | 7/37 |
| GastroenteritisInfections and infestations | 7/37 |
| Otitis mediaInfections and infestations | 7/37 |
| InfluenzaInfections and infestations | 6/37 |
Treated participants who received at least one dose of study drug (EFV) were analyzed.
| Age, Continuous(years) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| Median | 0.392 (0.296 to 0.501) | 0.825 (0.586 to 1.906) | 2.313 (2.094 to 2.995) | 3.922 (2.998 to 6.976) | 0.663 (0.296 to 6.976) |
| Sex: Female, Male(Participants) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| Female | 6 | 0 | 1 | 6 | 13 |
| Male | 9 | 10 | 3 | 2 | 24 |
| Race/Ethnicity, Customized(participants) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| White | 3 | 9 | 4 | 8 | 24 |
| Black or African American | 7 | 0 | 0 | 0 | 7 |
| Asian | 2 | 0 | 0 | 0 | 2 |
| Other | 3 | 1 | 0 | 0 | 4 |
| Region of Enrollment(participants) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| Panama | 3 | 0 | 0 | 1 | 4 |
| Mexico | 2 | 7 | 3 | 7 | 19 |
| Argentina | 0 | 3 | 1 | 0 | 4 |
| Thailand | 2 | 0 | 0 | 0 | 2 |
| South Africa | 7 | 0 | 0 | 0 | 7 |
| Colombia | 1 | 0 | 0 | 0 | 1 |
| Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) Viral Load (log10 c/mL)(log10 c/mL) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| Median | 5.88 (3.34 to 6.74) | 5.88 (2.12 to 5.88) | 5.88 (4.88 to 5.88) | 5.26 (3.38 to 5.88) | 5.88 (2.12 to 6.74) |
| HIV RNA Viral Load Category(participants) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| < 30,000 copies/mL | 3 | 1 | 0 | 1 | 5 |
| 30,000 to <100,000 copies/mL | 0 | 1 | 1 | 2 | 4 |
| 100,000 to <500,000 copies/mL | 2 | 1 | 0 | 2 | 5 |
| 500,000 to <=750,000 copies/mL | 1 | 1 | 0 | 1 | 3 |
| >750,000 copies/mL | 9 | 6 | 3 | 2 | 20 |
| CD4 Cell Count (n=13, 9, 3, 7, 32)(cells/mm^3) | EFV+ddI+FTC in Infants >=3 Months to < 6 Months | EFV+ddI+FTC in Infants >=6 Months to < 2 Years | EFV+ddI+FTC in Children >= 2 Years to < 3 Years | EFV+ddI+FTC in Children >= 3 Years to <= 6 Years | Total |
|---|---|---|---|---|---|
| Median | 1785 (200 to 3584) | 1569 (516 to 2879) | 517 (129 to 558) | 540 (11 to 1363) | 1144 (11 to 3584) |
The record gives a start of Feb 2007, a primary completion of Dec 2011 and a completion of Jul 2013. It does not say whether these dates are actual or estimated.
Results were first posted in Apr 2014, 2 years 4 months after primary completion.
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Studies of the drugs tested here: Efavirenz · Didanosine · Emtricitabine