Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3, Randomized Clinical Trial to Assess the Efficacy and Safety of Tenofovir in Hepatitis B Virus Infected, s and e Antigen Positive, Pregnant Women to Prevent Perinatal Transmission Despite Infant Passive-active HBV Immunization.
Brief Summary: Chronic hepatitis B (CHB) infection is complicated by cirrhosis and liver cancer. In Thailand, 7% of adults are chronically infected by Hepatitis B virus (HBV). The risk of perinatal transmission of HBV is about 12% when a mother has a high HBV load in her plasma, even if her infant receive specific immunoglobulin and vaccine.

The hypothesis of this study is that a potent antiviral, tenofovir, can decrease HBV load in HBV infected pregnant women and therefore reduce the risk of perinatal transmission/ Pregnant women participating in this study will receive tenofovir or placebo during the last trimester of pregnancy and two months postpartum. The risk of perinatal transmission will be compared between the two groups.

The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.


Options:
A: Inclusion Criteria:

* Pregnancy
* At least 18 years of age
* Negative Human Immunodeficiency Virus (HIV) serology
* Positive HBsAg and hepatitis B e antigen (HBeAg) tests
* Gestational age of 28 weeks (+ or - 10 days) as determined by obstetrician
* Alanine Aminotransferase (ALT)≤30 U/L, confirmed ≤60 U/L on a subsequent blood draw
* Agreeing to bring their infants at the planned study visits at one study site until one year after delivery and to inform the site investigators if they plan to move to another place and not be able to return to the clinic.
* Understanding the need for adequate infant immunization and agreeing to the blood draws from their infants and the need for close follow up to manage possible exacerbation of hepatitis.

Exclusion Criteria:

* History of tenofovir treatment at any time, or any other anti-HBV treatment during the current pregnancy
* Creatinine clearance \<50 ml/min, calculated using the Cockcroft-Gault formula
* Dipstick proteinuria\>1+ (\>30 mg/dL) or normoglycemic glucosuria confirmed on two separate occasions
* Positive serology for Hepatitis C infection less than 12 months prior to enrollment
* Evidence of pre-existing fetal anomalies incompatible with life
* Any concomitant condition or treatment that, in the view of the clinical site investigator, would contraindicate participation or satisfactory follow up in the study.
* Concurrent participation in any other clinical trial without written agreement of the two study teams
B: Key Inclusion Criteria:

* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
* Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
* Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA \< 50 copies/mL at the screening visit
* Normal echocardiograph (ECG)
* Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) ≤ 5 × upper limit of the normal range (ULN)
* Direct bilirubin ≤ 1.5 x ULN
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
* Female participants who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
* Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range

Key Exclusion Criteria:

* A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
* Hepatitis B surface antigen position
* Hepatitis C antibody positive
* Participants experiencing decompensated cirrhosis
* Females who are breastfeeding
* Positive serum pregnancy test
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial
* Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
C: Key Inclusion Criteria:

* Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec).
* Currently receiving an antiretroviral regimen of DTG + ABC/3TC, or ABC/DTG/3TC FDC for ≥ 3 months prior to the screening visit.
* HIV ribonucleic acid (RNA) \< 50 copies/mL at the screening visit.
* Currently on a stable regimen for ≥ 3 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 3 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
* Have no documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), DTG, ABC or 3TC.

Key Exclusion Criteria:

* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance.
* Active tuberculosis infection.
* Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
* Females who are pregnant.
* Females who are breastfeeding.
* Acute hepatitis in the 30 days prior to study entry.
* Chronic Hepatitis B Virus (HBV) infection.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
D: Antepartum Component Inclusion Criteria:

* Confirmed HIV-1 infection, defined as documented positive results from two samples collected at different time points prior to study entry. More information on this criterion can be found in the protocol.
* Currently pregnant and greater than or equal to 14 weeks gestation based on clinical or other obstetrical measurements
* CD4 count greater than or equal to 350 cells/mm\^3, or greater than or equal to the country-specific threshold for initiation of treatment (if that threshold is greater than 350 cells/mm\^3), on a specimen obtained within 30 days prior to study entry
* Results of HBV screening (HBsAg testing) available from specimen obtained within 30 days prior to study entry
* The following laboratory values from a specimen obtained within 30 days prior to study entry:

  1. Hemoglobin greater than or equal to 7.5 g/dL
  2. White blood cell count (WBC) greater than or equal to 1,500 cells/mm\^3
  3. Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm\^3
  4. Platelets greater than or equal to 50,000 cells/mm\^3
  5. Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal (ULN)
  6. Estimated creatinine clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation for women
* Plans to deliver in the study-affiliated clinic or hospital
* Has no plans to move outside of the study site area during the 24 months following delivery
* Age of legal majority for the respective country and willing and able to provide written informed consent

Antepartum Component Exclusion Criteria:

* Participation in PROMISE for a prior pregnancy
* Ingestion of any antiretroviral (ARV) regimen with three or more drugs (regardless of duration) or more than 30 days of a single or dual ARV regimen during current pregnancy, according to self report or available medical records
* Requires triple ARV therapy (HAART) for own health based on local standard guidelines
* World Health Organization (WHO) stage 4 disease
* Prior receipt of HAART for maternal treatment indications (e.g., CD4 less than 350 cells/mm\^3 or clinical indications); however, could have received ARVs for the sole purpose of prevention of mother-to-child transmission (PMTCT) in previous pregnancies (prior PMTCT regimens could have included a triple ARV regimen, ZDV, 3TC-ZDV, and/or sdNVP for PMTCT, as well as use of a short dual nucleoside reverse transcriptase inhibitor \[NRTI\] "tail" to reduce risk of NVP resistance.)
* In labor - at onset or beyond (may be eligible for the Late Presenter registration)
* Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
* Current or history of tuberculosis (TB) disease (positive PPD without TB disease is not exclusionary)
* Use of prohibited medications within 14 days prior to study entry (refer to the protocol for a list of prohibited medications)
* Fetus detected to have serious congenital malformation (ultrasound not required to rule out this condition)
* Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block \[also known as Mobitz I or Wenckebach\] is not considered exclusionary)
* Known to meet the local standard criteria for treatment of HBV (Note: HBV DNA testing or other specialized assessments are not expected to be performed as part of this study. A woman would be excluded only if this information is documented from other sources and she meets the local standard criteria for HBV treatment based on those assessments.)
* Social or other circumstances that would hinder long-term follow-up, in the opinion of the site investigator
* Currently incarcerated

Late Presenter Inclusion Criteria:

* Age of legal majority for the respective country
* HIV-1 infection, defined as documented positive results from tests performed on one sample at any time prior to Late Presenter Registration
* In labor (from onset/early labor or beyond) or within 5 days after delivery (with day of delivery considered day 0)
* Has provided written informed consent
* Has no plans to move outside of the study site area during the 24 months following delivery
* If delivered, infant alive and healthy (In the case of a multiple birth, a mother-infant pair will be included in the Late Presenter registration only if both/all infants and the mother meet the eligibility criteria. If only one infant of a multiple birth is alive, the M-I pair may be registered if the infant and the mother otherwise meet all of the eligibility criteria.)

Late Presenter Exclusion Criteria:

* Participation in PROMISE in prior pregnancy
* Ingestion of any antiretroviral regimen during current pregnancy (including for solely for PMTCT), according to self report and available medical records (Note: Use of ARVs provided as standard of care for PMTCT during labor/delivery or postpartum prior to Late Presenter registration is not exclusionary.)
* If known: CD4 count \< 350 cells/mm3 or below the country-specific threshold for initiation of treatment, if that threshold is \> 350 cells/mm3, on specimen obtained within 30 days prior to study entry (result not required prior to registration)
* Requires triple ARV therapy (HAART) for own health according to local standard guidelines
* WHO Stage 4 disease
* Prior receipt of HAART for maternal treatment indications (e.g., CD4 \< 350 cells/mm3 or clinical indications); however, could have received ARVs for the sole purpose of PMTCT in previous pregnancies. (Prior PMTCT regimens could have included a triple ARV regimen, ZDV, 3TCZDV and/or sdNVP for PMTCT, as well as use of a short dual NRTI "tail" to reduce risk of NVP resistance.)
* Current or history of TB disease (positive PPD without TB disease is not exclusionary)
* Known positive infant HIV nucleic acid test (NAT) result (result not required prior to registration)
* Fetal demise or early neonatal death (prior to enrollment/registration)
* Fetus detected with serious congenital malformation (ultrasound not required to rule out this condition)
* Life threatening infant illness or birth condition incompatible with life
* If delivered, infant birth weight \< 2.0 kg
* Social or other circumstances which would hinder long-term follow-up, in the opinion of the site investigator
* Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block (also known as Mobitz I or Wenckebach) is not considered exclusionary)

Postpartum Component Inclusion Criteria:

* Participation in the Antepartum Component or registered as a Late Presenter
* Provided written informed consent
* Has no plans to move outside of the study site area during the 24 months following delivery
* Maternal CD4 count greater than or equal to 350 cells/mm\^3, or greater than or equal to the country-specific threshold for initiation of treatment (if that threshold is greater than 350 cells/mm\^3), from a specimen obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol.
* The following maternal laboratory values within 30 days prior to entry:

  1. Hemoglobin greater than or equal to 7.0 g/dL
  2. WBC greater than or equal to 1,500 cells/mm\^3
  3. ANC greater than or equal to 750 cells/mm\^3
  4. Platelets greater than or equal to 50,000 cells/mm\^3
  5. ALT less than or equal to 2.5 times the upper limit of normal (ULN)
  6. Estimated creatinine clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation for women
* Infant alive, healthy, less than or equal to 14 days of age, and uninfected (negative HIV NAT result on specimen drawn prior to study entry)
* The following infant lab values on specimen obtained prior to study entry (within 14 days of birth):

  1. Hemoglobin greater than or equal to 10 g/dL
  2. WBC greater than or equal to 1,500 cells/mm\^3
  3. ANC greater than or equal to 750 cells/mm\^3
  4. Platelets greater than or equal to 50,000 cells/mm\^3
  5. ALT less than or equal to 2.5 times the ULN
* For Registered Late Presenters: Confirmed maternal HIV-1 infection, defined as documented positive results from two samples collected at different time points at any time prior to entry. More information on this criterion can be found in the protocol.

Postpartum Component Exclusion Criteria:

* Positive infant HIV NAT result on specimen drawn prior to entry or no infant HIV NAT result on specimen drawn prior to entry
* Life-threatening infant illness or birth condition incompatible with life
* Infant birth weight less than 2.0 kg
* Social or other circumstances that would hinder long-term follow-up, as judged by the site investigator
* Current or history of TB disease (positive PPD without TB disease is not exclusionary)
* Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block \[also known as Mobitz I or Wenckebach\] is not considered exclusionary)
* Requires triple ARV therapy (HAART) for own health

Maternal Health Component Inclusion Criteria:

* Randomly assigned to triple ARV prophylaxis as part of the Postpartum Component and has continued triple ARV prophylaxis until the current randomization without treatment interruption (defined as more than 14 consecutive days of missed dosing) within the previous 30 days; OR randomly assigned to triple ARV prophylaxis in the Antepartum Component but ineligible for the Postpartum Component and has continued triple ARV prophylaxis until the current randomization without treatment interruption (defined as more than 7 consecutive days of missed dosing) within the previous 30 days
* Within two weeks after complete breastfeeding cessation is achieved (defined as completely stopping all exposure to breast milk for greater than or equal to 28 days); i.e., within 29 to 42 days of last breast milk exposure, or reached 18 months postpartum (whichever comes first). Women who reach 18 months postpartum while still breastfeeding will be eligible for entry within 2 weeks before and 4 weeks after the Week 74 visit (Week 72-78); OR if the woman was randomized to triple ARV prophylaxis in the Postpartum Component and her infant is infected and still breastfeeding, she will be eligible for the Maternal Health Component within 42 days of specimen collection for the confirmatory infant HIV NAT; OR if the woman was randomized to triple ARV prophylaxis in the Antepartum Component but mother-infant pair was ineligible for the Postpartum Component she will be eligible for the Maternal Health Component beginning at the Week 1 visit (6-14 days postpartum) through 28 days after delivery; these women should be randomized as soon as possible, ideally within 6-14 days after delivery; OR if the woman was randomized to triple ARV prophylaxis in the Postpartum Component and breastfeeding risk for MTCT ceases for other reasons (e.g., infant death or permanent removal from home through legal services or adoption) within 28 days of event. More information on this criterion can be found in the protocol.
* Provided written informed consent
* CD4 cell count greater than or equal to 350 cells/mm\^3, or greater than or equal to the country-specific threshold for initiation of treatment (if that threshold is greater than 350 cells/mm\^3), on a specimen obtained within 30 days prior to study entry
* The following laboratory values on a specimen obtained within 30 days prior to study entry:

  1. ANC greater than or equal to 750 cells/mm\^3
  2. Hemoglobin greater than or equal to 7.0 gm/dL
  3. Platelet count greater than or equal to 50,000 cells/mm\^3
  4. ALT (SGPT) less than or equal to 2.5 times the ULN
  5. Estimated creatinine clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation for women
* Intend to remain in current geographical area of residence for the duration of study

Maternal Health Component Exclusion Criteria:

* WHO Stage 4 disease
* Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
* Current or history of TB disease (positive PPD without TB disease is not exclusionary)
* Use of prohibited medications within 14 days prior to study entry
* Social or other circumstances that would hinder long term follow-up as judged by the site investigator
* Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block \[also known as Mobitz I or Wenckebach\] is not considered exclusionary)
* Requires a triple ARV regimen for own health

Answer: A