HIV Infections
Conditions
Brief summary
The purpose of this study was to compare the virologic efficacy and safety of three antiretroviral (ARV) regimens, dolutegravir plus emtricitabine/tenofovir alafenamide, dolutegravir plus emtricitabine/tenofovir disoproxil fumarate, and efavirenz/emtricitabine/tenofovir disoproxil fumarate in pregnant women living with HIV-1 and to compare the safety of these regimens for their infants.
Detailed description
This study compared the virologic efficacy and safety of three ARV regimens in pregnant women living with HIV: dolutegravir (DTG) plus emtricitabine/tenofovir alafenamide (FTC/TAF), DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). The study also compared the safety of these regimens for their infants. At study entry, mothers were randomly assigned to either receive DTG plus FTC/TAF (Arm 1), DTG plus FTC/TDF (Arm 2), or EFV/FTC/TDF (Arm 3) during pregnancy, through delivery, and for 50 weeks postpartum. Mothers completed study visits at study entry and every four weeks during pregnancy. Study visits for mothers and their infants occurred at delivery and at 6, 14, 26, 38, and 50 weeks postpartum. Visits for mothers and infants included physical examinations and blood collection. Select study visits also included breast milk collection from mothers who breastfed, hair and urine collection, ultrasound scans, pregnancy testing, contraception counseling, and, for a subset of participants, dual energy x-ray absorptiometry (DXA) scans for mothers and their infants. For pregnancy outcome measures, mothers and infants were evaluated together as mother-infant pairs, with any outcome between the two counting as an event (for example, if an infant was born small for gestational age, this would be a pregnancy outcome event for the mother-infant pair). For all other outcome measures, women and infants were evaluated separately.
Interventions
DRUGDolutegravir
One 50 mg DTG tablet was administered orally once daily
One fixed-dose combination tablet (FTC 200 mg/TAF 25 mg) was administered orally once daily
DRUGEmtricitabine/tenofovir disoproxil fumarate
One fixed-dose combination tablet (FTC 200 mg/TDF 300 mg) was administered orally once daily
One fixed-dose combination tablet (EFV 600 mg/FTC 200 mg/TDF 300 mg) was administered orally once daily
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mother is able to provide written informed consent for her and her infant's participation in this study * Mother has confirmed HIV-1 infection based on documented testing of two samples collected at different time points: * Sample #1 may be tested using any of the following: * Two rapid antibody tests from different manufacturers or based on different principles and epitopes * One enzyme immunoassay (EIA) OR Western blot OR immunofluorescence assay OR chemiluminescence assay * One HIV DNA polymerase chain reaction (PCR) * One quantitative HIV RNA PCR (above the limit of detection of the assay) * One qualitative HIV RNA PCR * One total HIV nucleic acid test * Sample #2 may be tested using any of the following: * One rapid antibody test. If this option is used in combination with two rapid tests for Sample #1, at least one of the three rapid tests must be FDA-approved and the third rapid test must be from a third manufacturer or based on a third principle or epitope. * One EIA OR Western blot OR immunofluorescence assay OR chemiluminescence assay * One HIV DNA PCR * One quantitative HIV RNA PCR (above the limit of detection of the assay) * One qualitative HIV RNA PCR * One total HIV nucleic acid test. * See the protocol for more information on this inclusion criterion. * At screening, mother is ART-naive, defined as having not received prior antiretroviral therapy other than ARVs received during prior pregnancies or prior periods of breastfeeding (i.e., receipt of any single, dual, or triple ARV regimen during prior time-limited periods of pregnancy and breastfeeding is permitted). Receipt of up to 14 days of ARVs during the current pregnancy is permitted prior to study entry so that initiation of ARVs during the current pregnancy is not delayed during the study screening period. Note: Non-study ART may be initiated in the current pregnancy prior to initiation of the study screening process. For eligible participants, enrollment must occur within 14 days of non-study ART initiation. Note: Receipt of ARVs during a prior pregnancy or prior period of breastfeeding must have concluded at least six months prior to study entry. Receipt of TDF or FTC/TDF for pre-exposure prophylaxis at any time in the past is not exclusionary (even if received within six months prior to study entry). * At screening, mother has the following laboratory test results (based on testing of samples collected within 14 days prior to study entry): * Grade 1 or lower (less than 2.5 times upper limit of normal \[ULN\]) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) * Grade 2 or lower (less than or equal to 1.8 times ULN) creatinine * Grade 2 or lower (greater than or equal to 60 mL/min) estimated creatinine clearance (CrCl; Cockcroft-Gault formula). See the protocol for guidance on severity grading. Laboratory tests may be repeated during the study screening period, with the latest result used for eligibility determination. * At screening and at study entry, no evidence of multiple gestation or fetal anomalies, as assessed by best available method * At study entry, gestational age of 14-28 weeks, defined as greater than 13 weeks plus six days and less than 28 completed weeks gestation, estimated by best available method. Note: For this inclusion criterion and the previous inclusion criterion, fetal ultrasound is preferred but not required for purposes of eligibility determination. If ultrasound cannot be performed during the study screening period prior to study entry, it must be performed within 14 days after study entry. As further explained in the protocol, enrolled participants will not be withdrawn from the study based on ultrasound findings obtained after study entry. * At study entry, mother expects to remain in the geographic area of the study site during pregnancy and for 50 weeks postpartum \[Eligibility criteria added per Letter of Amendment 1 to V2; July 2018\]: * At study entry, mother reports that she does not wish to become pregnant again for at least 50 weeks after her current pregnancy and that she is willing to use effective contraception during this period. Effective contraception may include surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy) or any of the following methods: * Contraceptive intrauterine device (IUD) or intrauterine system (IUS) * Subdermal contraceptive implant * Progestogen injections * Progestogen only oral contraceptive pills * Combined estrogen and progestogen oral contraceptive pills * Percutaneous contraceptive patches * Contraceptive vaginal rings * Note: IUDs, IUSs, implants, and injections are strongly recommended due to their lower failure rates with typical use. Male or female condom use is recommended with all contraceptive methods for dual protection against pregnancy and to avoid transmission of HIV and other sexually transmitted infections.
Exclusion criteria
* Mother is currently incarcerated or involuntarily confined in a medical facility * Mother is currently receiving: * A psychoactive medication for treatment of a psychiatric illness * Treatment for active tuberculosis * Treatment for active hepatitis C infection * Mother is expected to require treatment with interferon and/or ribavirin for hepatitis C infection during the study follow-up period * Mother has a history of any of the following, as determined by the site investigator or designee based on maternal report and available medical records: * Hypersensitivity or clinically significant adverse reaction to any of the ARVs included in the three study drug regimens (ever) * Antiretroviral drug resistance mutations that would impact selection of ART regimen (ever) * Clinically significant heart disease and/or known prolonged corrected QT (QTc) interval (ever) * Suicidal ideation or attempt (ever) * HIV-2 infection (ever) * Zika virus infection, diagnosed or suspected, during the current pregnancy * Receipt of any antiretroviral medication within six months prior to study entry, with two exceptions: receipt of any duration of TDF or FTC/TDF for pre-exposure prophylaxis or receipt of up to 14 days of ARVs during the current pregnancy * Receipt of any prohibited medication within 14 days prior to study entry (see the protocol for more information) * Clinically significant acute illness requiring systemic treatment and/or hospitalization (i.e., major medical condition that is likely to lead to hospitalization and/or to an adverse pregnancy outcome) within 14 days prior to study entry * Unstable liver disease (defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice) or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) within 14 days prior to study entry * Note: Testing to rule out HIV-2 infection is not required. * Mother or fetus has any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery | Delivery | Percentage of mothers with plasma HIV-1 RNA viral load less than 200 copies/mL at delivery determined using real-time test results obtained at site laboratories. This outcome was evaluated in the non-inferiority (primary outcome) and superiority (secondary outcome) analyses. The intention-to-treat analysis included all randomized women who had viral load data available. The per-protocol analysis excluded women who modified randomized treatment (stopped, paused, switched, added any treatment) before viral load evaluation at delivery, with the exception of women who modified randomized treatment for use of a concomitant medication. |
| Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome | Delivery | Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (\<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (\<37 completed weeks), or small for gestational age (\<10th percentile by INTERGROWTH 21st Standards) |
| Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | From randomization up to 74 weeks | The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks. |
| Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | From birth through Week 50 postpartum | The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory | Delivery | Percentage of mothers with HIV-1 RNA less than 50 copies/mL at delivery using batched test results obtained from central laboratory |
| Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum | 50 weeks postpartum | Percentage of mothers with HIV-1 RNA less than 200 copies/mL at 50 weeks postpartum using real-time test results obtained from site laboratories |
| Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery | Randomization to delivery | Time to first viral HIV-1 RNA less than 200 copies/mL through delivery, determined using real-time results obtained from site laboratories |
| Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm | Delivery | Percentage of mothers with virologic success of HIV-1 RNA less than 200 copies/mL at delivery based on FDA snapshot algorithm using real-time test results obtained from site laboratories |
| Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm | 50 weeks postpartum | Percentage of mothers with virologic success of HIV-1 RNA less than 200 copies/mL at 50 weeks postpartum based on FDA snapshot algorithm using real-time test results obtained from site laboratories |
| Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome | Delivery | Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (\<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (\<37 completed weeks), or small for gestational age (\<10th percentile per INTERGROWTH 21st Standards) |
| Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | From randomization up to 74 weeks | The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks. |
| Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | Birth through Week 50 postpartum | The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. |
| Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly | Delivery through 50 weeks postpartum | Percentage of mother-infant pairs with an adverse pregnancy outcome or major congenital anomaly. Adverse pregnancy outcomes include spontaneous abortions (\<20 weeks gestation), stillbirths (≥20 weeks gestation), preterm deliveries (\<37 weeks gestation), and infants small for gestational age (\<10th percentile per INTERGROWTH 21st Standards). Major congenital anomaly was defined consistent with the definition of malformation provided by Holmes and Westgate (i.e., a structural abnormality with surgical, medical, or cosmetic importance) and evaluated by an internal study team blinded to treatment arm. |
| Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Birth through 50 weeks postpartum | Infant and pregnancy outcomes were classified on a scale of 1 to 10, with mother-infant pairs categorized by the worst outcome they experienced (worst category being 1 and best being 10): 1) Infant death; 2) Spontaneous abortion (\<20 weeks gestation) or stillbirth (≥20 weeks gestation); 3) Infant HIV infection; 4) Extremely and very early preterm (\<32 completed weeks); 5) Major congenital anomaly; 6) Preterm delivery (\<37 completed weeks); 7) Small for gestational age (\<10th percentile); 8) Infant hospitalization; 9) Infant grade 3 or 4 adverse event; 10) None of the above. If a mother-infant pair experienced more than one safety outcome, only the worst was reported. |
| Cumulative Probability of Infant HIV-infection | Birth through 50 weeks after birth | The Kaplan-Meier estimate of the cumulative probability of infants acquiring HIV-1 infection from birth through 50 weeks after birth based on nucleic acid test results. |
| Cumulative Probability of Infant Deaths | Birth through 50 weeks after birth | The Kaplan-Meier estimate of the cumulative probability of infant deaths from birth through 50 weeks after birth. |
| Maternal Change in Creatinine Clearance | Baseline to 50 weeks postpartum | Maternal change in creatinine clearance per week based on generalized estimating equations |
| Infant Creatinine Clearance | Delivery and 26 weeks postpartum | Infant creatinine clearance based on Schwartz formula |
| Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure | From 24 weeks after randomization through Week 50 postpartum | Percentage of mothers with HIV-1 antiretroviral (ARV) drug resistance mutations at the time of maternal virologic failure. Virologic failure was defined as two consecutive plasma HIV-1 RNA viral loads \<200 copies/mL on or after 24 weeks on study. Drug resistance mutations were assessed using the Stanford algorithm, and all ARV regimens were assessed for mutations. |
| Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis | From birth through 50 weeks postpartum | Count of infants with HIV-1 antiretroviral drug resistance mutations (to any antiretroviral drug) at the time of infant HIV diagnosis, based on laboratory blood test results. |
| Percentage of Mother-Infant Pairs With Preterm Deliveries | Delivery | Percentage of mother-infant pairs with preterm deliveries (\<37 weeks gestation) resulting in live born infant |
| Percentage of Infants Born Small for Gestational Age | Birth | Percentage of infants born small for gestational age (\<10th percentile adjusted for sex assigned at birth) based on Intergrowth 21st Standards |
| Change in Maternal Weight Antepartum | Baseline through before delivery (up to one day prior) | Change in maternal antepartum weight per week based on generalized estimating equations |
| Change in Maternal Weight Postpartum | Delivery to 50 weeks postpartum | Change in maternal postpartum weight per week based on generalized estimating equations |
| Change in Maternal Weight Overall | Baseline to 50 weeks postpartum | Change in maternal weight per week based on generalized estimating equations |
Countries
Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, United States, Zimbabwe
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Maternal DTG+FTC/TAF Mothers randomized to receive DTG+FTC/TAF | 217 |
| Arm 2: Maternal DTG+FTC/TDF Mothers randomized to receive DTG+FTC/TDF | 215 |
| Arm 3: Maternal EFV/FTC/TDF Mothers randomized to receive EFV/FTC/TDF | 211 |
| Total | 643 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 0 | 1 |
| Overall Study | Moved | 3 | 2 | 2 |
| Overall Study | Noncompliant with Study Requirements | 2 | 1 | 2 |
| Overall Study | Not Able to Get to Clinic | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 4 |
Baseline characteristics
| Characteristic | Arm 3: Maternal EFV/FTC/TDF | Arm 1: Maternal DTG+FTC/TAF | Arm 2: Maternal DTG+FTC/TDF | Total |
|---|---|---|---|---|
| Age, Continuous | 27.7 years STANDARD_DEVIATION 5.9 | 27.5 years STANDARD_DEVIATION 6.2 | 27.0 years STANDARD_DEVIATION 5.8 | 27.4 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 21 Participants | 21 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 190 Participants | 194 Participants | 192 Participants | 576 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Gestational Age | 21.8 weeks STANDARD_DEVIATION 4.2 | 21.6 weeks STANDARD_DEVIATION 4.2 | 21.4 weeks STANDARD_DEVIATION 4.2 | 21.6 weeks STANDARD_DEVIATION 4.2 |
| Gestational Age Stratification Group 14-18 Weeks | 59 Participants | 58 Participants | 64 Participants | 181 Participants |
| Gestational Age Stratification Group 19-23 Weeks | 77 Participants | 93 Participants | 83 Participants | 253 Participants |
| Gestational Age Stratification Group 24-28 Weeks | 75 Participants | 66 Participants | 68 Participants | 209 Participants |
| Plasma HIV-1 RNA Viral Load | 13,381.2 copies/mL | 14,558.2 copies/mL | 18,420.3 copies/mL | 15,471.2 copies/mL |
| Plasma HIV-1 RNA Viral Load <200 copies/mL | 53 Participants | 62 Participants | 66 Participants | 181 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants | 7 Participants | 5 Participants | 18 Participants |
| Race/Ethnicity, Customized Race Black or African American | 194 Participants | 195 Participants | 196 Participants | 585 Participants |
| Race/Ethnicity, Customized Race Other | 4 Participants | 10 Participants | 6 Participants | 20 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 7 Participants | 5 Participants | 7 Participants | 19 Participants |
| Region of Enrollment Botswana | 17 Participants | 16 Participants | 18 Participants | 51 Participants |
| Region of Enrollment Brazil | 17 Participants | 21 Participants | 19 Participants | 57 Participants |
| Region of Enrollment India | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment South Africa | 37 Participants | 37 Participants | 37 Participants | 111 Participants |
| Region of Enrollment Tanzania | 15 Participants | 15 Participants | 13 Participants | 43 Participants |
| Region of Enrollment Thailand | 6 Participants | 5 Participants | 4 Participants | 15 Participants |
| Region of Enrollment Uganda | 36 Participants | 37 Participants | 37 Participants | 110 Participants |
| Region of Enrollment United States | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Zimbabwe | 83 Participants | 82 Participants | 84 Participants | 249 Participants |
| Sex: Female, Male Female | 211 Participants | 217 Participants | 215 Participants | 643 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 64.5 kg STANDARD_DEVIATION 13.3 | 67.7 kg STANDARD_DEVIATION 15.1 | 66.3 kg STANDARD_DEVIATION 16.8 | 66.2 kg STANDARD_DEVIATION 15.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 217 | 0 / 215 | 0 / 211 | 2 / 208 | 4 / 202 | 14 / 207 |
| other Total, other adverse events | 189 / 217 | 198 / 215 | 143 / 211 | 34 / 208 | 40 / 202 | 34 / 207 |
| serious Total, serious adverse events | 39 / 217 | 39 / 215 | 40 / 211 | 35 / 208 | 29 / 202 | 44 / 207 |
Outcome results
Primary
Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
Time frame: From birth through Week 50 postpartum
Population: Live born infants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | 25.3 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | 28.6 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | 30.9 Cumulative probability per 100 persons |
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimated difference of DTG+FTC/TAF - DTG+FTC/TDF.p-value: 0.2595% CI: [-12.8, 6.3]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimate of risk difference DTG+FTC/TDF-EFV/FTC/TDF.p-value: 0.3295% CI: [-12.1, 7.5]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimate of risk difference DTG+FTC/TAF-EFV/FTC/TDF.p-value: 0.1195% CI: [-14.3, 3.2]Z-test
Primary
Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks.
Time frame: From randomization up to 74 weeks
Population: Enrolled women.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | 25.1 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | 30.8 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | 27.9 Cumulative probability per 100 persons |
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Survival probabilities were compared based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.09895% CI: [-14.2, 2.9]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Survival probabilities were compared based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms (DTG+FTC/TDF-EFV/FTC/TDF).p-value: 0.2695% CI: [-5.9, 11.7]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Survival probabilities were compared based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms (DTG+FTC/TAF-EFV/FTC/TDF).p-value: 0.2695% CI: [-11.3, 5.8]Z-test
Primary
Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome
Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (\<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (\<37 completed weeks), or small for gestational age (\<10th percentile by INTERGROWTH 21st Standards)
Time frame: Delivery
Population: Mother-infant pairs with pregnancy outcome evaluated on study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome | 24.1 percentage of mother-infant pairs |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome | 32.9 percentage of mother-infant pairs |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome | 32.7 percentage of mother-infant pairs |
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.04395% CI: [-17.3, -0.3]Wald test of two proportions
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.9795% CI: [-8.8, 9.1]Wald test of two proportions
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.04795% CI: [-17.1, -0.1]Wald test of two proportions
Primary
Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery
Percentage of mothers with plasma HIV-1 RNA viral load less than 200 copies/mL at delivery determined using real-time test results obtained at site laboratories. This outcome was evaluated in the non-inferiority (primary outcome) and superiority (secondary outcome) analyses. The intention-to-treat analysis included all randomized women who had viral load data available. The per-protocol analysis excluded women who modified randomized treatment (stopped, paused, switched, added any treatment) before viral load evaluation at delivery, with the exception of women who modified randomized treatment for use of a concomitant medication.
Time frame: Delivery
Population: Women who had plasma HIV-1 RNA viral load data available at delivery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery | Intention-to-Treat Analysis | 97.5 Percentage of participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery | Per-Protocol Analysis | 97.5 Percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery | Intention-to-Treat Analysis | 91.0 Percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery | Per-Protocol Analysis | 91.4 Percentage of participants |
Comparison: Difference in proportions for intention-to-treat analysis.95% CI: [2, 10.7]
Comparison: Difference in proportions for per-protocol analysis.95% CI: [1.6, 10.3]
Comparison: Difference in proportions for superiority and intention-to-treat analysis.p-value: 0.00595% CI: [2, 10.7]Wald test of two proportions
Secondary
Change in Maternal Weight Antepartum
Change in maternal antepartum weight per week based on generalized estimating equations
Time frame: Baseline through before delivery (up to one day prior)
Population: Women with weight data available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Change in Maternal Weight Antepartum | 0.378 kg/week |
| Arm 3: Maternal EFV/FTC/TDF | Change in Maternal Weight Antepartum | 0.319 kg/week |
| Arm 3: Maternal EFV/FTC/TDF | Change in Maternal Weight Antepartum | 0.291 kg/week |
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.01195% CI: [0.013, 0.103]Generalized Estimating Equation
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.1995% CI: [-0.014, 0.07]Generalized Estimating Equation
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TAF - EFV/FTC/TDF).p-value: <0.00195% CI: [0.04, 0.133]Generalized Estimating Equation
Secondary
Change in Maternal Weight Overall
Change in maternal weight per week based on generalized estimating equations
Time frame: Baseline to 50 weeks postpartum
Population: Women with weight data available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Change in Maternal Weight Overall | -0.027 kg/week |
| Arm 3: Maternal EFV/FTC/TDF | Change in Maternal Weight Overall | -0.050 kg/week |
| Arm 3: Maternal EFV/FTC/TDF | Change in Maternal Weight Overall | -0.084 kg/week |
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.04195% CI: [0.001, 0.045]Generalized Estimating Equation
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.00295% CI: [0.013, 0.055]Generalized Estimating Equation
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TAF - EFV/FTC/TDF).p-value: <0.00195% CI: [0.036, 0.078]Generalized Estimating Equation
Secondary
Change in Maternal Weight Postpartum
Change in maternal postpartum weight per week based on generalized estimating equations
Time frame: Delivery to 50 weeks postpartum
Population: Women with weight data available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Change in Maternal Weight Postpartum | 0.014 kg/week |
| Arm 3: Maternal EFV/FTC/TDF | Change in Maternal Weight Postpartum | -0.008 kg/week |
| Arm 3: Maternal EFV/FTC/TDF | Change in Maternal Weight Postpartum | -0.032 kg/week |
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.1195% CI: [-0.005, 0.048]Generalized Estimating Equation
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.05595% CI: [0, 0.049]Generalized Estimating Equation
Comparison: Null hypothesis of no difference between arms (DTG+FTC/TAF - EFV/FTC/TDF).p-value: <0.00195% CI: [0.022, 0.07]Generalized Estimating Equation
Secondary
Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis
Count of infants with HIV-1 antiretroviral drug resistance mutations (to any antiretroviral drug) at the time of infant HIV diagnosis, based on laboratory blood test results.
Time frame: From birth through 50 weeks postpartum
Population: Infants who had an HIV diagnosis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis | 1 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis | 0 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis | 1 Participants |
Secondary
Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome
Infant and pregnancy outcomes were classified on a scale of 1 to 10, with mother-infant pairs categorized by the worst outcome they experienced (worst category being 1 and best being 10): 1) Infant death; 2) Spontaneous abortion (\<20 weeks gestation) or stillbirth (≥20 weeks gestation); 3) Infant HIV infection; 4) Extremely and very early preterm (\<32 completed weeks); 5) Major congenital anomaly; 6) Preterm delivery (\<37 completed weeks); 7) Small for gestational age (\<10th percentile); 8) Infant hospitalization; 9) Infant grade 3 or 4 adverse event; 10) None of the above. If a mother-infant pair experienced more than one safety outcome, only the worst was reported.
Time frame: Birth through 50 weeks postpartum
Population: Mother-infant pairs with pregnancy outcome evaluated on study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Death | 2 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Spontaneous abortion or stillbirth | 8 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | HIV-1 Infection | 2 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Extremely and Very Preterm Delivery | 1 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Major Congenital Anomaly | 2 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Preterm Delivery | 10 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Small for Gestational Age | 29 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Hospitalization | 18 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Grade 3 or 4 Adverse Event | 7 Participants |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | None | 137 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Grade 3 or 4 Adverse Event | 8 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Death | 4 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Preterm Delivery | 17 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Major Congenital Anomaly | 0 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Spontaneous abortion or stillbirth | 11 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | None | 120 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Hospitalization | 14 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | HIV-1 Infection | 0 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Small for Gestational Age | 38 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Extremely and Very Preterm Delivery | 1 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Hospitalization | 19 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Extremely and Very Preterm Delivery | 2 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Major Congenital Anomaly | 1 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Preterm Delivery | 18 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Grade 3 or 4 Adverse Event | 6 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Small for Gestational Age | 36 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Infant Death | 14 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | None | 110 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | Spontaneous abortion or stillbirth | 4 Participants |
| Arm 3: Maternal EFV/FTC/TDF | Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome | HIV-1 Infection | 1 Participants |
Comparison: Null hypothesis of odds ratio equal to 1, with odds of experiencing a worse outcome equal between groups (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.09595% CI: [0.5, 1.06]Regression, Ordinal
Comparison: Null hypothesis of odds ratio equal to 1, with odds of experiencing a worse outcome equal between groups (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.395% CI: [0.58, 1.19]Regression, Ordinal
Comparison: Null hypothesis of odds ratio equal to 1, with odds of experiencing a worse outcome equal between groups (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.00895% CI: [0.42, 0.88]Regression, Ordinal
Secondary
Cumulative Probability of Infant Deaths
The Kaplan-Meier estimate of the cumulative probability of infant deaths from birth through 50 weeks after birth.
Time frame: Birth through 50 weeks after birth
Population: Live born infants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Cumulative Probability of Infant Deaths | 1.0 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infant Deaths | 2.0 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infant Deaths | 6.9 Cumulative probability per 100 persons |
p-value: 0.295% CI: [-3.4, 1.3]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimate of risk difference DTG+FTC/TDF-EFV/FTC/TDF.p-value: 0.00895% CI: [-8.9, -0.9]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimate of risk difference DTG+FTC/TAF-EFV/FTC/TDF.p-value: <0.00195% CI: [-9.7, -2.2]Z-test
Secondary
Cumulative Probability of Infant HIV-infection
The Kaplan-Meier estimate of the cumulative probability of infants acquiring HIV-1 infection from birth through 50 weeks after birth based on nucleic acid test results.
Time frame: Birth through 50 weeks after birth
Population: Live born infants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Cumulative Probability of Infant HIV-infection | 0.98 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infant HIV-infection | 0.50 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infant HIV-infection | 0.55 Cumulative probability per 100 persons |
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Survival probabilities were compared based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.2895% CI: [-1.2, 2.1]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Survival probabilities were compared based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.4795% CI: [-1.5, 1.4]Z-test
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Survival probabilities were compared based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.3195% CI: [-1.3, 2.2]Z-test
Secondary
Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
Time frame: Birth through Week 50 postpartum
Population: Live born infants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | 26.8 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event | 30.9 Cumulative probability per 100 persons |
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimated difference of combined DTG arms - EFV/FTC/TDF.p-value: 0.1595% CI: [-3.8, 12]Z-test
Secondary
Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks.
Time frame: From randomization up to 74 weeks
Population: Enrolled women.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | 27.9 Cumulative probability per 100 persons |
| Arm 3: Maternal EFV/FTC/TDF | Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event | 27.9 Cumulative probability per 100 persons |
Comparison: The Kaplan-Meier method was used to estimate survival probabilities. Comparisons of survival probabilities was based on a Z-test using Greenwoods estimate of the standard error. The null hypothesis was no difference between arms, with estimate of risk difference combined DTG arms-EFV/FTC/TDF.p-value: 0.4995% CI: [-7.6, 7.5]Z-test
Secondary
Infant Creatinine Clearance
Infant creatinine clearance based on Schwartz formula
Time frame: Delivery and 26 weeks postpartum
Population: Live born infants with creatinine clearance data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Infant Creatinine Clearance | Delivery | 52.7 mL/min | Standard Deviation 29.6 |
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Infant Creatinine Clearance | 26 Weeks Postpartum | 134.8 mL/min | Standard Deviation 109.6 |
| Arm 3: Maternal EFV/FTC/TDF | Infant Creatinine Clearance | Delivery | 53.1 mL/min | Standard Deviation 69.7 |
| Arm 3: Maternal EFV/FTC/TDF | Infant Creatinine Clearance | 26 Weeks Postpartum | 123.6 mL/min | Standard Deviation 40.3 |
| Arm 3: Maternal EFV/FTC/TDF | Infant Creatinine Clearance | Delivery | 49.0 mL/min | Standard Deviation 24.7 |
| Arm 3: Maternal EFV/FTC/TDF | Infant Creatinine Clearance | 26 Weeks Postpartum | 135.0 mL/min | Standard Deviation 51.1 |
Comparison: Null hypothesis of no difference between arms at delivery (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.9495% CI: [-11.3, 10.5]t-test, 2 sided
Comparison: Null hypothesis of no difference between arms at delivery (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.4495% CI: [-6.5, 14.9]t-test, 2 sided
Comparison: Null hypothesis of no difference between arms at delivery (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.1895% CI: [-1.8, 9.3]t-test, 2 sided
Comparison: Null hypothesis of no difference between arms at week 26 (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.2795% CI: [-8.9, 31.1]t-test, 2 sided
Comparison: Null hypothesis of no difference between arms at week 26 (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.04895% CI: [-22.6, -0.1]t-test, 2 sided
Comparison: Null hypothesis of no difference between arms at week 26 (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.9895% CI: [-21, 20.5]t-test, 2 sided
Secondary
Maternal Change in Creatinine Clearance
Maternal change in creatinine clearance per week based on generalized estimating equations
Time frame: Baseline to 50 weeks postpartum
Population: Women with creatinine clearance data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Maternal Change in Creatinine Clearance | -0.980 mL/min |
| Arm 3: Maternal EFV/FTC/TDF | Maternal Change in Creatinine Clearance | -0.887 mL/min |
| Arm 3: Maternal EFV/FTC/TDF | Maternal Change in Creatinine Clearance | -0.935 mL/min |
Comparison: Null hypothesis of no difference in weekly change in creatinine clearance from baseline (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.1295% CI: [-0.208, 0.023]Generalized Estimating Equation
Comparison: Null hypothesis of no difference in weekly change in creatinine clearance from baseline (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.3995% CI: [-0.061, 0.158]Generalized Estimating Equation
Comparison: Null hypothesis of no difference in weekly change in creatinine clearance from baseline (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.4595% CI: [-0.161, 0.072]Generalized Estimating Equation
Secondary
Percentage of Infants Born Small for Gestational Age
Percentage of infants born small for gestational age (\<10th percentile adjusted for sex assigned at birth) based on Intergrowth 21st Standards
Time frame: Birth
Population: Live born infants with weight and sex data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Infants Born Small for Gestational Age | 16.3 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Infants Born Small for Gestational Age | 22.5 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Infants Born Small for Gestational Age | 20.5 percentage of participants |
p-value: 0.1295% CI: [-13.9, 1.5]Wald test of two proportions
p-value: 0.6395% CI: [-6, 10]Wald test of two proportions
p-value: 0.2895% CI: [-11.7, 3.4]Wald test of two proportions
Secondary
Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome
Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (\<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (\<37 completed weeks), or small for gestational age (\<10th percentile per INTERGROWTH 21st Standards)
Time frame: Delivery
Population: Mother-infant pairs with pregnancy outcome evaluated on study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome | 28.4 percentage of mother-infant pairs |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome | 32.7 percentage of mother-infant pairs |
Comparison: Null hypothesis of no difference between groups (DTG groups - EFV/FTC/TDF).p-value: 0.2795% CI: [-3.4, 11.9]Wald test of two proportions
Secondary
Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly
Percentage of mother-infant pairs with an adverse pregnancy outcome or major congenital anomaly. Adverse pregnancy outcomes include spontaneous abortions (\<20 weeks gestation), stillbirths (≥20 weeks gestation), preterm deliveries (\<37 weeks gestation), and infants small for gestational age (\<10th percentile per INTERGROWTH 21st Standards). Major congenital anomaly was defined consistent with the definition of malformation provided by Holmes and Westgate (i.e., a structural abnormality with surgical, medical, or cosmetic importance) and evaluated by an internal study team blinded to treatment arm.
Time frame: Delivery through 50 weeks postpartum
Population: Mother-infant pairs with pregnancy outcome evaluated on study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly | 24.1 percentage of mother-infant pairs |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly | 32.9 percentage of mother-infant pairs |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly | 33.2 percentage of mother-infant pairs |
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.04395% CI: [-17.3, -0.3]Wald test of two proportions
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.9595% CI: [-9.3, 8.6]Wald test of two proportions
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.03795% CI: [-17.6, -0.6]Wald test of two proportions
Secondary
Percentage of Mother-Infant Pairs With Preterm Deliveries
Percentage of mother-infant pairs with preterm deliveries (\<37 weeks gestation) resulting in live born infant
Time frame: Delivery
Population: Women with pregnancies resulting in a live born infant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mother-Infant Pairs With Preterm Deliveries | 5.8 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-Infant Pairs With Preterm Deliveries | 9.4 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mother-Infant Pairs With Preterm Deliveries | 12.1 percentage of participants |
p-value: 0.3895% CI: [-8.7, 3.3]Wald test of two proportions
p-value: 0.02395% CI: [-11.8, -0.9]Wald test of two proportions
p-value: 0.1695% CI: [-8.8, 1.5]Wald test of two proportions
Secondary
Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure
Percentage of mothers with HIV-1 antiretroviral (ARV) drug resistance mutations at the time of maternal virologic failure. Virologic failure was defined as two consecutive plasma HIV-1 RNA viral loads \<200 copies/mL on or after 24 weeks on study. Drug resistance mutations were assessed using the Stanford algorithm, and all ARV regimens were assessed for mutations.
Time frame: From 24 weeks after randomization through Week 50 postpartum
Population: All enrolled women
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure | 0.92 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure | 1.86 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure | 6.16 percentage of participants |
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.495% CI: [-3.1, 1.3]Wald test of two proportions
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.02395% CI: [-8, -0.6]Wald test of two proportions
Comparison: Null hypothesis of no difference between groups (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.00395% CI: [-8.7, -1.8]Wald test of two proportions
Secondary
Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum
Percentage of mothers with HIV-1 RNA less than 200 copies/mL at 50 weeks postpartum using real-time test results obtained from site laboratories
Time frame: 50 weeks postpartum
Population: Women with viral load data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum | 96.3 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum | 96.4 percentage of participants |
Comparison: Difference in proportions for intention-to-treat analysis with null hypothesis of no difference between arms (DTG arms - EFV/FTC/TDF).p-value: 0.9795% CI: [-3.3, 3.2]Wald test of two proportions
Secondary
Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory
Percentage of mothers with HIV-1 RNA less than 50 copies/mL at delivery using batched test results obtained from central laboratory
Time frame: Delivery
Population: Women with viral load data available from central laboratory
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory | 94.4 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory | 78.8 percentage of participants |
Comparison: Difference in proportions between arms for intention-to-treat analysis with null hypothesis of no difference (DTG groups - EFV/FTC/TDF).p-value: <0.000195% CI: [9.3, 22]Wald test of two proportions
Secondary
Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm
Percentage of mothers with virologic success of HIV-1 RNA less than 200 copies/mL at 50 weeks postpartum based on FDA snapshot algorithm using real-time test results obtained from site laboratories
Time frame: 50 weeks postpartum
Population: Enrolled women
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm | 75.6 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm | 77.7 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm | 76.3 percentage of participants |
Comparison: Difference between arms with null hypothesis of no difference (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.6195% CI: [-5.9, 10.1]Wald test of two proportions
Comparison: Difference between arms with null hypothesis of no difference (DTG+FTC/TDF - EFV/FTC/TDF).p-value: 0.7495% CI: [-9.4, 6.6]Wald test of two proportions
Comparison: Difference between arms with null hypothesis of no difference (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.8695% CI: [-7.4, 8.8]Wald test of two proportions
Secondary
Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm
Percentage of mothers with virologic success of HIV-1 RNA less than 200 copies/mL at delivery based on FDA snapshot algorithm using real-time test results obtained from site laboratories
Time frame: Delivery
Population: Enrolled women
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm | 88.9 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm | 92.6 percentage of participants |
| Arm 3: Maternal EFV/FTC/TDF | Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm | 81.0 percentage of participants |
Comparison: Difference between arms with null hypothesis of no difference (DTG+FTC/TAF - DTG+FTC/TDF).p-value: 0.1995% CI: [-1.8, 9.1]Wald test of two proportions
Comparison: Difference between arms with null hypothesis of no difference (DTG+FTC/TDF - EFV/FTC/TDF).p-value: <0.00195% CI: [-17.9, -5.2]Wald test of two proportions
Comparison: Difference between arms with null hypothesis of no difference (DTG+FTC/TAF - EFV/FTC/TDF).p-value: 0.02295% CI: [-14.6, -1.2]Wald test of two proportions
Secondary
Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery
Time to first viral HIV-1 RNA less than 200 copies/mL through delivery, determined using real-time results obtained from site laboratories
Time frame: Randomization to delivery
Population: Women with viral load data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF | Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery | 4.26 weeks | Standard Error 0.09 |
| Arm 3: Maternal EFV/FTC/TDF | Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery | 6.49 weeks | Standard Error 0.31 |
p-value: <0.00195% CI: [1.9, 3.1]Kaplan-Meier