Arthralgia, HIV Infections, Infection, Human Immunodeficiency Virus
Conditions
Keywords
dolutegravir/abacavir/lamivudine fixed dose combination, pregnant women, once daily, antiretroviral therapy-naive, HIV-1 Infection, integrase inhibitor
Brief summary
In this study, the dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose combination (FDC) tablet is being made available to women who become pregnant while participating in study ING117172. Continuation of antiretroviral therapy (ART) is key to both mother and the unborn fetus in order to maintain virologic suppression in the mother (thereby decreasing the risk for maternal disease progression), but also to reduce the risk of maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1) to her unborn child. This study also offers the first opportunity to investigate the impact of pregnancy on DTG pharmacokinetics (PK). This is an open-label, single arm interventional study. The number of women that will be enrolled into this study cannot be established a priori, as unintended pregnancies cannot be determined in advance. The maximum number of women would include all of those women randomized to DTG/ABC/3TC FDC (approximately 237), though unintended pregnancies in all of these women would not be anticipated.
Interventions
DRUGDTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablets
The DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablet is a purple, oval, biconvex tablets. The tablet contains 52.6 mg DTG sodium which is equivalent to 50 mg DTG free acid, 702 mg ABC sulphate which is equivalent to 600 mg ABC and 300 mg 3TC.
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV infected females participating in ING117172 on the DTG/ABC/3TC treatment arm who became pregnant with a singleton and have not met any safety or confirmed virologic withdrawal criteria. * Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening. * Willingness and intent to continue pregnancy * Willingness to continue to receive DTG/ABC/3TC FDC. * Willingness to enter the Antiretroviral Pregnancy Registry. * Willingness to share medical information about herself and her infant for collection of delivery and infant outcomes as it relates to this study. * Subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria
* History of allergy/sensitivity to DTG, ABC and/or 3TC. * History of severe pre-clampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP) * Any evidence of an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy or historic or current CD4+ cell levels \<200 cells/millimeter\^3. * Subjects with any degree of hepatic impairment. * Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject. * Subjects who in the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk. * Subjects with evidence of ongoing hepatitis B infection at screening, or anticipated need for Hepatitis C Virus therapy during the study. * Treatment with any of the following agents within 28 days of Baseline: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses. * Subjects enrolled in France: the subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study. * Any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities (total cholesterol, triglycerides, high density lipoprotein \[HDL\] cholesterol, low density lipoprotein \[LDL\] cholesterol). A single repeat test is allowed during the Screening period to verify a result. * Any acute laboratory abnormality observed in ING117172 or in any Screening laboratory assessments for ING200336, which, in the opinion of the Investigator, would preclude the subject's participation in the study. * Hyperbilirubinemia of unknown etiology. * Confirmed (with no more than 1 repeat evaluation) Grade \>= 2 urine protein (dipstick), serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase at the time of the screening lab. * Subject has Creatinine Clearance of \<50 mL/minute via Cockroft-Gault method at the time of the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades | Up to 292 Weeks | Number of participants (pregnant women) with adverse events (AE) as per severity grades were presented. Grade 1 is mild, grade 2 is moderate, grade 3 is severe or medically significant but not immediately life-threatening and grade 4 is life-threatening consequences; urgent intervention required. |
| Maximum Observed Plasma Concentration (Cmax) for Dolutegravir | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir | 24 hours post dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Apparent Oral Clearance (CL/F) for Dolutegravir | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Half-life (T1/2) for Dolutegravir | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin | Up to Week 32 of study | Blood samples were collected for analysis of hemoglobin. Any abnormality was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Number of participants (Pregnant Women) with maximum severity of post-Baseline emergent toxicities with respect to hemoglobin has been presented. |
| Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of chemistry parameters including ALT and AST. |
| Change From Baseline in Chemistry Parameters: ALT and AST | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of chemistry parameters including ALT and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. |
| Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Absolute Values of the Hematology Parameters: Hemoglobin | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of hematology parameters including hemoglobin. |
| Change From Baseline in Hematology Parameters: Hemoglobin | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of hematology parameters including hemoglobin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Absolute Values of the Hematology Parameters: Leukocytes and Platelets | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. |
| Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study | Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Number of Participants (Pregnant Women) Who Discontinued the Treatment Due to Adverse Events (AE) | Up to Week 292 | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment. Number of participants (pregnant women) who discontinued the treatment due to adverse events have been presented. |
| Number of Participants (Pregnant Women) Demonstrated Congenital Malformations | At delivery (up to Week 40 of pregnancy) | Data for participants (pregnant women) demonstrated congenital malformations was reported. |
| Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for Pharmacokinetic (PK) analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre-dose Plasma Concentration (C0) for Dolutegravir | Pre-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 3 hours and 24 hours post dose in Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery | At delivery (up to Week 40 of pregnancy) | Blood samples were collected at the time of delivery for PK analysis of dolutegravir. |
| Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria | Up to Week 32 of study | Number of participants (pregnant women) with treatment-emergent genotypic and/or phenotypic resistance who met confirmed virologic withdrawal criteria are presented. Genotypic and phenotypic analyses were carried out by Monogram Biosciences using, but not limited to, their Standard Phenosense and GenoSure testing methods for protease (PRO) and reverse transcriptase (RT), or with their GeneSeq Integrase and PhenoSense Integrase assays. |
| Number of Participants (Pregnant Women) With Live Birth Outcome Categories | At delivery (up to Week 40 of pregnancy) | Participants (pregnant women) with following live birth outcome categories are reported- Vaginal Birth, Planned Caesarean Section, Unscheduled Caesarean Section and Preterm Delivery. |
| Gestational Age of Infants | At birth | Gestational age is defined as the number of weeks between the first day of the mother's last normal menstrual period and the day of birth. Data for gestational age of infants has been presented. |
| Neonatal Length and Head Circumference at Birth | At birth | Data for neonatal length and head circumference at birth are reported. |
| Neonatal Weight at Birth | At birth | Data for neonatal weight at birth has been reported. |
| Number of Infants by Their Weight Categories at Birth | At birth | Weight of infants at birth were categorized as: Small for Gestational Age (SGA) defined neonates under the 10th percentile in weight, Appropriate for Gestational Age (AGA) characterized neonates between the 10th and 90th percentiles in weight and Large for Gestational Age (LGA) referred to neonates over the 90th percentile in weight. |
| Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth | 1 and 5 minutes after birth | APGAR is a quick test to assess the health of new born. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two with 2 being the best score, then summing up the values obtained from all five categories. APGAR score ranges from 0 to 10 (Higher score indicates better health) where a score of 7 and above is normal. Number of infants by APGAR score at 1 and 5 minutes after birth are presented. |
| Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study | Percentage of participants (pregnant women) with plasma HIV-1 RNA \<50 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA. |
| Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study | Percentage of participants (pregnant women) with plasma HIV-1 RNA \<400 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA. |
| Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study | Blood samples were collected for the analysis of CD4+ T cell counts using cytometry. |
| Change From Baseline in CD4+ T Cell Counts by Visit | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study | Blood samples were collected for the analysis of CD4+ T cell counts using cytometry. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Number of Participants (Pregnant Women) With Disease Progression | Up to Week 32 of study | Disease progression included HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death. Number of participants (pregnant women) with disease progression to Centers for Disease Control and Prevention (CDC) class C or death have been presented. |
| Time to Cmax (Tmax) for Dolutegravir | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
Countries
Russia, Spain
Participant flow
Recruitment details
This is a single arm open-label study in women who became pregnant while participating in study ING117172 (NCT01910402).
Pre-assignment details
In this study, 4 pregnant women were enrolled. Participant flow data was collected only in pregnant women (enrolled population/study participants) and not in infants, as infants were not considered as enrolled per study design.
Participants by arm
| Arm | Count |
|---|---|
| DTG/ABC/3TC - Mother Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | DTG/ABC/3TC - Mother |
|---|---|
| Age, Continuous | 29.3 Years STANDARD_DEVIATION 5.56 |
| Race/Ethnicity, Customized White/Caucasian/European heritage | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 0 |
| other Total, other adverse events | 4 / 4 | 0 / 0 |
| serious Total, serious adverse events | 1 / 4 | 0 / 0 |
Outcome results
Primary
Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Blood samples were collected for the analysis of chemistry parameters including ALT and AST.
Time frame: At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1), n=4 | 10.8 International units per Liter | Standard Deviation 5.56 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 4, n=4 | 15.3 International units per Liter | Standard Deviation 4.43 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 8, n=4 | 19.3 International units per Liter | Standard Deviation 17.21 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 12, n=4 | 11.0 International units per Liter | Standard Deviation 3.16 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 16, n=4 | 10.8 International units per Liter | Standard Deviation 2.36 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 20, n=4 | 10.3 International units per Liter | Standard Deviation 7.27 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 24, n=1 | 19.0 International units per Liter | — |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Week 32, n=2 | 28.0 International units per Liter | Standard Deviation 15.56 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1), n=4 | 14.8 International units per Liter | Standard Deviation 4.19 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 4, n=4 | 17.3 International units per Liter | Standard Deviation 2.22 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 8, n=4 | 17.3 International units per Liter | Standard Deviation 6.18 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 12, n=4 | 15.0 International units per Liter | Standard Deviation 1.83 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 16, n=4 | 14.8 International units per Liter | Standard Deviation 2.63 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 20, n=4 | 16.3 International units per Liter | Standard Deviation 3.3 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 24, n=1 | 20.0 International units per Liter | — |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Week 32, n=2 | 24.0 International units per Liter | Standard Deviation 8.49 |
Primary
Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine
Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine.
Time frame: At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 32, n=2 | 68.90 Micromoles per Liter | Standard Deviation 3.677 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Baseline (Day 1), n=4 | 7.3 Micromoles per Liter | Standard Deviation 3.77 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 4, n=4 | 5.0 Micromoles per Liter | Standard Deviation 1.83 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 8, n=4 | 5.5 Micromoles per Liter | Standard Deviation 2.65 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 12, n=4 | 4.5 Micromoles per Liter | Standard Deviation 1.29 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 16, n=4 | 4.5 Micromoles per Liter | Standard Deviation 1.29 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 20, n=4 | 4.5 Micromoles per Liter | Standard Deviation 1.29 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 24, n=1 | 7.0 Micromoles per Liter | — |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 32, n=2 | 6.5 Micromoles per Liter | Standard Deviation 0.71 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Baseline (Day 1), n=4 | 57.73 Micromoles per Liter | Standard Deviation 16.661 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 4, n=4 | 50.50 Micromoles per Liter | Standard Deviation 2.99 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 8, n=4 | 51.58 Micromoles per Liter | Standard Deviation 3.067 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 12, n=4 | 50.68 Micromoles per Liter | Standard Deviation 3.293 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 16, n=4 | 47.45 Micromoles per Liter | Standard Deviation 2.001 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 20, n=4 | 50.60 Micromoles per Liter | Standard Deviation 6.424 |
| DTG/ABC/3TC - Mother | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 24, n=1 | 63.60 Micromoles per Liter | — |
Primary
Absolute Values of the Hematology Parameters: Hemoglobin
Blood samples were collected for the analysis of hematology parameters including hemoglobin.
Time frame: At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Baseline (Day 1), n=4 | 127.8 Grams per Liter | Standard Deviation 11.24 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 4, n=4 | 120.8 Grams per Liter | Standard Deviation 7.23 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 8, n=4 | 113.5 Grams per Liter | Standard Deviation 7.05 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 12, n=4 | 116.5 Grams per Liter | Standard Deviation 7.14 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 16, n=4 | 115.0 Grams per Liter | Standard Deviation 4.69 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 20, n=4 | 115.8 Grams per Liter | Standard Deviation 8.3 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 24, n=1 | 127.0 Grams per Liter | — |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Hemoglobin | Week 32, n=2 | 140.5 Grams per Liter | Standard Deviation 0.71 |
Primary
Absolute Values of the Hematology Parameters: Leukocytes and Platelets
Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets.
Time frame: At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Baseline (Day 1), n=4 | 6.48 Giga cells per Liter | Standard Deviation 1.415 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 4, n=4 | 7.88 Giga cells per Liter | Standard Deviation 2.095 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 8, n=4 | 8.43 Giga cells per Liter | Standard Deviation 1.959 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 12, n=4 | 9.15 Giga cells per Liter | Standard Deviation 2.053 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 16, n=4 | 9.23 Giga cells per Liter | Standard Deviation 1.821 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 20, n=4 | 10.03 Giga cells per Liter | Standard Deviation 2.848 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 24, n=1 | 12.60 Giga cells per Liter | — |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 32, n=2 | 5.85 Giga cells per Liter | Standard Deviation 0.636 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Baseline (Day 1), n=4 | 204.8 Giga cells per Liter | Standard Deviation 37.03 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 4, n=4 | 200.5 Giga cells per Liter | Standard Deviation 2.38 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 8, n=4 | 220.8 Giga cells per Liter | Standard Deviation 16.07 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 12, n=4 | 195.5 Giga cells per Liter | Standard Deviation 25.38 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 16, n=4 | 198.0 Giga cells per Liter | Standard Deviation 10.8 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 20, n=4 | 216.5 Giga cells per Liter | Standard Deviation 10.91 |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 24, n=1 | 250.0 Giga cells per Liter | — |
| DTG/ABC/3TC - Mother | Absolute Values of the Hematology Parameters: Leukocytes and Platelets | Platelets, Week 32, n=2 | 206.0 Giga cells per Liter | Standard Deviation 24.04 |
Primary
Apparent Oral Clearance (CL/F) for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Apparent Oral Clearance (CL/F) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 0.739 Liters per hour |
| DTG/ABC/3TC - Mother | Apparent Oral Clearance (CL/F) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 0.952 Liters per hour |
| DTG/ABC/3TC - Mother | Apparent Oral Clearance (CL/F) for Dolutegravir | 8-12 Weeks Postpartum | 0.464 Liters per hour |
Primary
Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir
Blood samples were collected at indicated timepoints for Pharmacokinetic (PK) analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population consists of all participants in the Safety Population (comprised of all participants \[pregnant women\] who received at least one dose of study treatment) who had at least 1 non-missing PK assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 55.045 Micrograms*hours per milliliter |
| DTG/ABC/3TC - Mother | Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 42.473 Micrograms*hours per milliliter |
| DTG/ABC/3TC - Mother | Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir | 8-12 Weeks postpartum | 78.917 Micrograms*hours per milliliter |
Primary
Change From Baseline in Chemistry Parameters: ALT and AST
Blood samples were collected for the analysis of chemistry parameters including ALT and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 4, n=4 | 4.5 International units per Liter | Standard Deviation 6.03 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 8, n=4 | 8.5 International units per Liter | Standard Deviation 11.79 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 12, n=4 | 0.3 International units per Liter | Standard Deviation 3.3 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 16, n=4 | 0.0 International units per Liter | Standard Deviation 3.56 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 20, n=4 | -0.5 International units per Liter | Standard Deviation 1.73 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 24, n=1 | 0.0 International units per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | ALT, Week 32, n=2 | 19.5 International units per Liter | Standard Deviation 14.85 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 4, n=4 | 2.5 International units per Liter | Standard Deviation 4.43 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 8, n=4 | 2.5 International units per Liter | Standard Deviation 2.38 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 12, n=4 | 0.3 International units per Liter | Standard Deviation 3.1 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 16, n=4 | 0.0 International units per Liter | Standard Deviation 3.37 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 20, n=4 | 1.5 International units per Liter | Standard Deviation 1.29 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 24, n=1 | -1.0 International units per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: ALT and AST | AST, Week 32, n=2 | 11.0 International units per Liter | Standard Deviation 8.49 |
Primary
Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine
Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 4, n=4 | -2.3 Micromoles per Liter | Standard Deviation 2.06 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 8, n=4 | -1.8 Micromoles per Liter | Standard Deviation 1.26 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 12, n=4 | -2.8 Micromoles per Liter | Standard Deviation 2.99 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 16, n=4 | -2.8 Micromoles per Liter | Standard Deviation 2.99 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 20, n=4 | -2.8 Micromoles per Liter | Standard Deviation 2.99 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 24, n=1 | -5.0 Micromoles per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Bilirubin, Week 32, n=2 | 2.0 Micromoles per Liter | Standard Deviation 2.83 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 4, n=4 | -7.23 Micromoles per Liter | Standard Deviation 14.014 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 8, n=4 | -6.15 Micromoles per Liter | Standard Deviation 16.7 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 12, n=4 | -7.05 Micromoles per Liter | Standard Deviation 14.328 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 16, n=4 | -10.28 Micromoles per Liter | Standard Deviation 17.453 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 20, n=4 | -7.13 Micromoles per Liter | Standard Deviation 11.154 |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 24, n=1 | -19.10 Micromoles per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine | Creatinine, Week 32, n=2 | 19.10 Micromoles per Liter | Standard Deviation 3.253 |
Primary
Change From Baseline in Hematology Parameters: Hemoglobin
Blood samples were collected for the analysis of hematology parameters including hemoglobin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 4, n=4 | -7.0 Grams per Liter | Standard Deviation 10.17 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 8, n=4 | -14.3 Grams per Liter | Standard Deviation 7.37 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 12, n=4 | -11.3 Grams per Liter | Standard Deviation 4.92 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 16, n=4 | -12.8 Grams per Liter | Standard Deviation 6.65 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 20, n=4 | -12.0 Grams per Liter | Standard Deviation 4.97 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 24, n=1 | -14.0 Grams per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Hemoglobin | Week 32, n=2 | 14.0 Grams per Liter | Standard Deviation 8.49 |
Primary
Change From Baseline in Hematology Parameters: Leukocytes and Platelets
Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 4, n=4 | 1.40 Giga cells per Liter | Standard Deviation 1.817 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 8, n=4 | 1.95 Giga cells per Liter | Standard Deviation 2.047 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 12, n=4 | 2.68 Giga cells per Liter | Standard Deviation 1.173 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 16, n=4 | 2.75 Giga cells per Liter | Standard Deviation 1.654 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 20, n=4 | 3.55 Giga cells per Liter | Standard Deviation 2.34 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 24, n=1 | 4.90 Giga cells per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Leukocytes, Week 32, n=2 | -0.65 Giga cells per Liter | Standard Deviation 1.061 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 4, n=4 | -4.3 Giga cells per Liter | Standard Deviation 39.09 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 8, n=4 | 16.0 Giga cells per Liter | Standard Deviation 33.44 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 12, n=4 | -9.3 Giga cells per Liter | Standard Deviation 39.08 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 16, n=4 | -6.8 Giga cells per Liter | Standard Deviation 47.16 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 20, n=4 | 11.8 Giga cells per Liter | Standard Deviation 45.49 |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 24, n=1 | 10.0 Giga cells per Liter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Platelets, Week 32, n=2 | -4.0 Giga cells per Liter | Standard Deviation 50.91 |
Primary
Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: 24 hours post dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 930.1 Nanograms per milliliter |
| DTG/ABC/3TC - Mother | Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 657.5 Nanograms per milliliter |
| DTG/ABC/3TC - Mother | Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir | 8-12 Weeks Postpartum | 2154.7 Nanograms per milliliter |
Primary
Half-life (T1/2) for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Half-life (T1/2) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 9.215 Hours | Standard Deviation 1.8968 |
| DTG/ABC/3TC - Mother | Half-life (T1/2) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 9.401 Hours | Standard Deviation 3.0322 |
| DTG/ABC/3TC - Mother | Half-life (T1/2) for Dolutegravir | 8-12 Weeks Postpartum | 9.699 Hours | Standard Deviation 3.0427 |
Primary
Maximum Observed Plasma Concentration (Cmax) for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Maximum Observed Plasma Concentration (Cmax) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 4.420 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Maximum Observed Plasma Concentration (Cmax) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 3.424 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Maximum Observed Plasma Concentration (Cmax) for Dolutegravir | 8-12 Weeks Postpartum | 5.578 Micrograms per milliliter |
Primary
Number of Participants (Pregnant Women) Demonstrated Congenital Malformations
Data for participants (pregnant women) demonstrated congenital malformations was reported.
Time frame: At delivery (up to Week 40 of pregnancy)
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) Demonstrated Congenital Malformations | 0 Participants |
Primary
Number of Participants (Pregnant Women) Who Discontinued the Treatment Due to Adverse Events (AE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment. Number of participants (pregnant women) who discontinued the treatment due to adverse events have been presented.
Time frame: Up to Week 292
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) Who Discontinued the Treatment Due to Adverse Events (AE) | 0 Participants |
Primary
Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades
Number of participants (pregnant women) with adverse events (AE) as per severity grades were presented. Grade 1 is mild, grade 2 is moderate, grade 3 is severe or medically significant but not immediately life-threatening and grade 4 is life-threatening consequences; urgent intervention required.
Time frame: Up to 292 Weeks
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades | Grade 1 | 2 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades | Grade 2 | 2 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades | Grade 3 | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades | Grade 4 | 0 Participants |
Primary
Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin
Blood samples were collected for analysis of hemoglobin. Any abnormality was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Number of participants (Pregnant Women) with maximum severity of post-Baseline emergent toxicities with respect to hemoglobin has been presented.
Time frame: Up to Week 32 of study
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin | Grade 1 | 1 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin | Grade 2 | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin | Grade 3 | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin | Grade 4 | 0 Participants |
Primary
Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 9.665 Liters |
| DTG/ABC/3TC - Mother | Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 12.326 Liters |
| DTG/ABC/3TC - Mother | Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir | 8-12 Weeks Postpartum | 6.326 Liters |
Secondary
Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit
Blood samples were collected for the analysis of CD4+ T cell counts using cytometry.
Time frame: At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study
Population: Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Baseline (Day 1), n=4 | 476.3 Cells per cubic millimeter | Standard Deviation 123.31 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 4, n=4 | 569.5 Cells per cubic millimeter | Standard Deviation 238.51 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 8, n=4 | 569.8 Cells per cubic millimeter | Standard Deviation 296.43 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 12, n=4 | 575.0 Cells per cubic millimeter | Standard Deviation 331.22 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 16, n=4 | 626.8 Cells per cubic millimeter | Standard Deviation 270.63 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 20, n=4 | 791.5 Cells per cubic millimeter | Standard Deviation 524.96 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 24, n=2 | 874.5 Cells per cubic millimeter | Standard Deviation 516.9 |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 28, n=1 | 488.0 Cells per cubic millimeter | — |
| DTG/ABC/3TC - Mother | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit | Week 32, n=2 | 677.5 Cells per cubic millimeter | Standard Deviation 40.31 |
Secondary
Change From Baseline in CD4+ T Cell Counts by Visit
Blood samples were collected for the analysis of CD4+ T cell counts using cytometry. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study
Population: Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 4, n=4 | 93.3 Cells per cubic millimeter | Standard Deviation 124.64 |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 8, n=4 | 93.5 Cells per cubic millimeter | Standard Deviation 174.54 |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 12, n=4 | 98.8 Cells per cubic millimeter | Standard Deviation 208.5 |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 16, n=4 | 150.5 Cells per cubic millimeter | Standard Deviation 148.73 |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 20, n=4 | 315.3 Cells per cubic millimeter | Standard Deviation 402 |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 24, n=2 | 353.0 Cells per cubic millimeter | Standard Deviation 332.34 |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 28, n=1 | 98.0 Cells per cubic millimeter | — |
| DTG/ABC/3TC - Mother | Change From Baseline in CD4+ T Cell Counts by Visit | Week 32, n=2 | 246.0 Cells per cubic millimeter | Standard Deviation 97.58 |
Secondary
Gestational Age of Infants
Gestational age is defined as the number of weeks between the first day of the mother's last normal menstrual period and the day of birth. Data for gestational age of infants has been presented.
Time frame: At birth
Population: Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Gestational Age of Infants | 38.3 Weeks | Standard Deviation 1.71 |
Secondary
Neonatal Length and Head Circumference at Birth
Data for neonatal length and head circumference at birth are reported.
Time frame: At birth
Population: Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Neonatal Length and Head Circumference at Birth | Neonatal Length | 51.5 Centimeter | Standard Deviation 3.11 |
| DTG/ABC/3TC - Mother | Neonatal Length and Head Circumference at Birth | Neonatal Head Circumference | 34.9 Centimeter | Standard Deviation 1.65 |
Secondary
Neonatal Weight at Birth
Data for neonatal weight at birth has been reported.
Time frame: At birth
Population: Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Neonatal Weight at Birth | 3262.5 Grams | Standard Deviation 731.36 |
Secondary
Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth
APGAR is a quick test to assess the health of new born. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two with 2 being the best score, then summing up the values obtained from all five categories. APGAR score ranges from 0 to 10 (Higher score indicates better health) where a score of 7 and above is normal. Number of infants by APGAR score at 1 and 5 minutes after birth are presented.
Time frame: 1 and 5 minutes after birth
Population: Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth | 1 Minute, Score 0 to 6 | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth | 1 Minute, Score 7 to 10 | 4 Participants |
| DTG/ABC/3TC - Mother | Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth | 5 Minute, Score 0 to 6 | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth | 5 Minute, Score 7 to 10 | 4 Participants |
Secondary
Number of Infants by Their Weight Categories at Birth
Weight of infants at birth were categorized as: Small for Gestational Age (SGA) defined neonates under the 10th percentile in weight, Appropriate for Gestational Age (AGA) characterized neonates between the 10th and 90th percentiles in weight and Large for Gestational Age (LGA) referred to neonates over the 90th percentile in weight.
Time frame: At birth
Population: Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Number of Infants by Their Weight Categories at Birth | LGA | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Infants by Their Weight Categories at Birth | AGA | 4 Participants |
| DTG/ABC/3TC - Mother | Number of Infants by Their Weight Categories at Birth | SGA | 0 Participants |
Secondary
Number of Participants (Pregnant Women) With Disease Progression
Disease progression included HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death. Number of participants (pregnant women) with disease progression to Centers for Disease Control and Prevention (CDC) class C or death have been presented.
Time frame: Up to Week 32 of study
Population: Intent-to-Treat Exposed Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Disease Progression | 0 Participants |
Secondary
Number of Participants (Pregnant Women) With Live Birth Outcome Categories
Participants (pregnant women) with following live birth outcome categories are reported- Vaginal Birth, Planned Caesarean Section, Unscheduled Caesarean Section and Preterm Delivery.
Time frame: At delivery (up to Week 40 of pregnancy)
Population: Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Live Birth Outcome Categories | Vaginal Birth | 1 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Live Birth Outcome Categories | Planned Caesarean Section | 2 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Live Birth Outcome Categories | Unscheduled Caesarean Section | 1 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Live Birth Outcome Categories | Preterm Delivery | 1 Participants |
Secondary
Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria
Number of participants (pregnant women) with treatment-emergent genotypic and/or phenotypic resistance who met confirmed virologic withdrawal criteria are presented. Genotypic and phenotypic analyses were carried out by Monogram Biosciences using, but not limited to, their Standard Phenosense and GenoSure testing methods for protease (PRO) and reverse transcriptase (RT), or with their GeneSeq Integrase and PhenoSense Integrase assays.
Time frame: Up to Week 32 of study
Population: Intent-to-Treat Exposed (ITT-E) Population includes all participants (pregnant women) who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria | Participants with genotypic resistance | 0 Participants |
| DTG/ABC/3TC - Mother | Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria | Participants with phenotypic resistance | 0 Participants |
Secondary
Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit
Percentage of participants (pregnant women) with plasma HIV-1 RNA \<400 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
Time frame: At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study
Population: Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 4, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 8, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 12, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 16, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 20, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 24, n=2 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 28, n=1 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit | Week 32, n=2 | 100 Percentage of participants |
Secondary
Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit
Percentage of participants (pregnant women) with plasma HIV-1 RNA \<50 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
Time frame: At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study
Population: Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 4, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 8, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 12, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 16, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 20, n=4 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 24, n=2 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 28, n=1 | 100 Percentage of participants |
| DTG/ABC/3TC - Mother | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit | Week 32, n=2 | 100 Percentage of participants |
Secondary
Pre-dose Plasma Concentration (C0) for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Pre-dose Plasma Concentration (C0) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 666.9 Nanograms per milliliter |
| DTG/ABC/3TC - Mother | Pre-dose Plasma Concentration (C0) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 1084.6 Nanograms per milliliter |
| DTG/ABC/3TC - Mother | Pre-dose Plasma Concentration (C0) for Dolutegravir | 8-12 Weeks Postpartum | 1225.0 Nanograms per milliliter |
Secondary
Time to Cmax (Tmax) for Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Time to Cmax (Tmax) for Dolutegravir | Trimester 2 (Weeks 18-26 of pregnancy) | 3.508 Hours | Standard Deviation 1.7082 |
| DTG/ABC/3TC - Mother | Time to Cmax (Tmax) for Dolutegravir | Trimester 3 (Weeks 30-36 of pregnancy) | 2.729 Hours | Standard Deviation 0.4877 |
| DTG/ABC/3TC - Mother | Time to Cmax (Tmax) for Dolutegravir | 8-12 Weeks Postpartum | 4.242 Hours | Standard Deviation 2.0522 |
Secondary
Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery
Blood samples were collected at the time of delivery for PK analysis of dolutegravir.
Time frame: At delivery (up to Week 40 of pregnancy)
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTG/ABC/3TC - Mother | Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery | Cord plasma concentration | 1436.0 Nanograms per milliliter | Standard Deviation 1287.43 |
| DTG/ABC/3TC - Mother | Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery | Maternal plasma concentration | 1806.3 Nanograms per milliliter | Standard Deviation 1125.04 |
Secondary
Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Time frame: At 3 hours and 24 hours post dose in Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| DTG/ABC/3TC - Mother | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 3 hours post dose in Trimester 2 | 7.856 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 3 hours post dose in Trimester 3 | 7.371 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 3 hours post dose 8-12 Weeks postpartum | 6.898 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 24 hours post dose in Trimester 2 | 1.798 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 24 hours post dose in Trimester 3 | 2.065 Micrograms per milliliter |
| DTG/ABC/3TC - Mother | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir | At 24 hours post dose 8-12 Weeks postpartum | 2.881 Micrograms per milliliter |