Evaluating the Efficacy and Safety of Dolutegravir-Containing Versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and Their Infants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Dolutegravir; Emtricitabine/tenofovir alafenamide; Emtricitabine/tenofovir disoproxil fumarate; Efavirenz/emtricitabine/tenofovir disoproxil fumarate
Intervention description: 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; 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
Intervention MeSH terms: Tenofovir; Emtricitabine; Efavirenz; Dolutegravir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine tenofovir alafenamide; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 643.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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