HIV Infections
Conditions
Keywords
Mother to Child Transmission, HIV Infection, HAART, Maternal Health, Breastfeeding, Perinatal transmission
Brief summary
The purpose of this study was to examine, in an integrated and comprehensive fashion, three critical questions currently facing HIV-infected pregnant and postpartum women and their infants: 1. What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV? 2. What is the optimal intervention for the prevention of postpartum transmission in breastfeeding (BF) infants? 3. What is the optimal intervention for the preservation of maternal health after the risk period for prevention of mother-to-child-transmission ends (either at delivery or cessation of BF)? The overall PROMISE protocol had three separate interventional components to address each of these three questions and was conducted at locations in Africa and other parts of the world. Due to variations in the standard of care for HIV-infected pregnant and postpartum women and their infants at different sites, not all of these questions were relevant. Therefore, two separate versions of the PROMISE protocol were developed, each containing only the relevant components. The 1077BF protocol was used at sites where the standard method of infant feeding was breastfeeding, whereas the 1077FF protocol was used at sites where the standard method of infant feeding was formula feeding. The analyses were collapsed across the two protocol versions, and therefore the summaries contain the results of the 1077BF and/or the 1077FF protocols.
Detailed description
The incidence of mother-to-child transmission (MTCT) of HIV has decreased in recent years in the United States, Europe, and other resource-advantaged countries. Several factors have contributed to this decrease, including the administration of HAART during pregnancy, caesarean section delivery methods, and the use of formula instead of breastfeeding to feed infants. However, in resource-limited countries, the incidence of pediatric HIV infection remains high. Many pregnant women in these countries do not receive an adequate course of HAART, and the majority breastfeed their children. This study was divided into three components (Antepartum, Postpartum, and Maternal Health Components). The following is a description of each of the three open label sequential randomization components, each designed to address one of the following three main objectives: 1. Antepartum Component: This PROMISE component compared the safety and efficacy of different HAART regimens for preventing the transmission of HIV during pregnancy, labor, and delivery. * Participants were randomly assigned to one of the following three arms: * Maternal Regimens: * Arm A : 1) Zidovudine (ZDV) from study entry through delivery, 2) single dose nevirapine (sdNVP) and emtricitabine-tenofovir disoproxil (TRV ) intrapartum, and 3) TRV postpartum for up to 14 days post-partum. Arm A is also labeled as ZDV+sdNVP+TRV tail. * Arm B: Lamivudine (3TC)-zidovudine (ZDV) + lopinavir (LPV)-ritonavir (RTV) from study entry up to 14 days postpartum. Arm B is also labeled as 3TC-ZDV/LPV-RTV. * Arm C: TRV/LPV-RTV from study entry up to 14 days postpartum. Arm C is also labeled as FTC-TDF/LPV-RTV. * All infants born to women enrolled in this study were to receive NVP once a day as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever was later. Women switched or initiated HAART if it was needed for their own health. * During pregnancy, participants attended study visits at study entry, 2 and 4 weeks after entry, and then every 4 weeks until labor and delivery. Women and infants were monitored during labor and delivery and attended a study visit 6 to 14 days after delivery. After delivery, eligibility criteria were assessed for subsequent randomizations (either Postpartum or Maternal Health). If they failed the entry criteria for the subsequent randomization, the mothers remained in follow-up for safety assessments and the infants were followed until the 104 week visit; otherwise they were followed under the subsequent component. * All three antepartum arms were not available to all women throughout the PROMISE study. When the trial began, there were limited safety data on tenofovir in pregnancy, and randomization to tenofovir-based ART was limited to women coinfected with HIV and HBV, because benefit was felt to outweigh risk in that group. During period 1 (PROMISE protocol version 2.0 - April 2011 through September 2012), women without HBV coinfection were randomized to either Arm A or Arm B; and Hepatitis B (HBV) co-infected women were randomized to either Arm A, Arm B, or Arm C. However, in October 2012, with increased data on tenofovir in pregnancy, the protocol was modified to allow women regardless of HBV status to be assigned to any of the three regimens during period 2 (PROMISE protocol version 3.0 - October 2012 through the end of antepartum enrollment on October 1, 2014). By arm comparisons were restricted to times in which there were contemporaneous randomizations. * Late Presenters: In addition the Antepartum Component, participants could enter PROMISE through the Late Presenters Registration (LP). Late presenters were identified in early or active labor or in the immediate postpartum period (up to 5 days postpartum). The Late Presenters Registration facilitated a structure to screen women and infants for randomization in the Postpartum Component. Women and infants not randomized in the Postpartum Component of PROMISE were followed through the Week 6 visit. * There were 3543 mothers and 3407 live born infants enrolled in the Antepartum Component. There were 204 mothers and 204 live born infants in the Late Presenters Registration. 2. Postpartum Component: This PROMISE component compared the safety and efficacy of maternal triple ARV prophylaxis versus daily infant NVP prophylaxis for the prevention of mother-to-child transmission (PMTCT) through breastfeeding. The Postpartum Component consisted of mothers and infants from the Antepartum Component and the Late Presenters Registration who passed the Postpartum Component entry criteria. * Participants were randomly assigned to one of two arms: * Arm A: Women received LPV-RTV plus TRV from the Week 1 postpartum visit through the end of maternal follow-up (2 to 5 years). Infants received NVP once a day through 42 days of age or until the Week 6 study visit, whichever was later. * Arm B: Infants received NVP once a day from the Week 1 postpartum visit until the end of risk for MTCT or until 18 months postpartum (104 weeks). Women did not receive antiretroviral drugs for MTCT prophylaxis. * The maternal study visits were at entry, at postpartum weeks 6, 14, 26, and every 12 weeks thereafter. Infant study visits were at entry, every 4 weeks between postpartum weeks 6-26, every 12 weeks between postpartum week 38-98, and at postpartum week 104. At the end of risk for MTCT or 18 months postpartum, the mothers' eligibility criteria were assessed for a subsequent randomization in the Maternal Health Component. If they did not meet entry criteria for the Maternal Health randomization, they remained in follow-up for safety assessments; otherwise they were followed under the Maternal Health Component. Infants were followed until the 104 week visit. * Women switched or initiated HAART if it was needed for their own health. If a woman in Arm B initiated HAART then her infant discontinued NVP after 12 weeks of HAART or after her viral load was suppressed, whichever came first. * There were 2431 mothers and 2444 infants randomized as part of the Postpartum Component. 3. Maternal Health Component: This PROMISE component randomized women to continue or discontinue HAART after the end of risk for MTCT, either after delivery or after breastfeeding. Participants included women who were receiving the triple ARV regimen in the Postpartum Component; or receiving the triple ARV regimen in the Antepartum Component and were ineligible for the Postpartum Component. * Participants were randomly assigned to one of two study arms: * Arm A: Participants continued to receive the triple ARV regimen (preferred regimen was LPV-RTV plus TRV). * Arm B: Participants discontinued the triple ARV regimen. * Study visits occurred at Weeks 4 and 12 and then every 3 months thereafter. Study visits included a medical history review, questionnaires, physical exam, and blood collection. Women switched or initiated a triple ARV regimen if it was needed for their own health. * There were 875 mothers randomized as part of the Maternal Health Component. * The analyses for the Maternal Health Component we not solely based on the Maternal Health Randomization. Instead there were four prespecified comparison groups for the Maternal Health Component. The four comparison groups used the three randomizations as appropriate to answer the following questions: * Question 1: What is the effect on women of using a maternal triple ARV regimen to prevent MTCT during pregnancy, relative to using ZDV + sdNVP + TRV tail to prevent MTCT during pregnancy? * Question 2: What is the effect on women of using a maternal triple ARV regimen to prevent MTCT during breastfeeding, relative to using infant NVP to prevent MTCT during breastfeeding? * Question 3: What is the effect on women of extending versus discontinuing the antepartum/intrapartum maternal triple ARV regimen at the time of birth? * Question 4: What is the effect on women of extending versus discontinuing the postpartum maternal triple ARV regimen after the cessation of risk for MTCT during breastfeeding? * There were 1602 mothers included in the analyses for Question 2. PROMISE mothers were followed for 2 to 5 years, depending on when they enrolled. Infants were followed up to 104 weeks of age. Infant and maternal follow-up ended in September 2016. PROMISE randomizations were halted in the summer of 2014 due to slow accrual to the Later Presenters Registration and the Formula Feeding protocol. Due to the results of an external study, on July 7th 2015 the PROMISE interventions were halted and ART was offered to all participants. Per recommendation from the Data and Safety and Monitoring Board on November 4th 2014, the primary analyses for the Antepartum Component include follow-up through September 10th, 2014. Per recommendation from the Data and Safety and Monitoring Board on November 12th 2015, the primary analyses for the Postpartum Component include follow-up through July 7th, 2015. The Adverse Events in the Reported Adverse Event section include all study follow-up.
Interventions
DRUGZidovudine (ZDV)
300 mg twice daily
DRUGNevirapine (NVP): Antepartum Mothers
200 mg at onset of labor
DRUGEmtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail
200 mg/300 mg x 2 tablets at onset of labor or as soon as possible thereafter; 200 mg/300 mg orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.
DRUGLamivudine-Zidovudine (3TC-ZDV)
150 mg/300 mg twice daily
DRUGLopinavir-ritonavir (LPV-RTV)
400 mg/100 mg twice daily beginning at \>= 14 weeks gestation; 600 mg/150 mg twice daily beginning at \>= 28 weeks gestation or at next visit (during third trimester) through delivery; 400 mg/100 mg twice daily after delivery up to 14 days postpartum.
DRUGEmtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])
200 mg/300 mg
DRUGNevirapine (NVP): Infant short-course
Oral suspension (dosing according to birth weight) once a day through 42 days of age or through the week 6 visit, whichever is later.
DRUGNevirapine (NVP): Infant extended
Oral suspension (dosing according to birth weight) once a day from 6 (up to 14) days of age until there was no longer any risk of MTCT or until the end of follow-up (104 weeks), whichever came first.
OTHERNo Intervention
Women registered before/during labor received the full Antepartum Arm A regimen. Women registered after labor, and who received nevirapine outside of the study, received the Emtricitabine-tenofovir disoproxil fumarate (Truvada \[TRV\]) tail.
OTHERDiscontinue triple ARVs
ARVs were discontinued. When protocol specified criteria were met, mothers could be prescribed any licensed antiretroviral medication, as long as the treatment met the definition of HAART (three ARV drugs from two or more drug classes).
OTHERContinue triple ARVs
Mothers could be prescribed any licensed antiretroviral medication, as long as the treatment met the definition of HAART (three ARV drugs from two or more drug classes).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The investigators and outcomes assessor did not receive by-arm tabulations while the study was ongoing.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antepartum Component: Number of Confirmed Infant HIV Infections | Measured at birth or Week 1 study visit | Defined as HIV nucleic acid test (NAT) positivity of the specimen drawn at either the birth (Day 0-5) or Week 1 (Day 6-14) visit, confirmed by HIV NAT positivity of a second specimen collected at a different time point |
| Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses in Appendix IV of the protocol. These events were reviewed and confirmed by an Endpoint review group. |
| Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first | These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com). |
| Postpartum Component: Incidence of Confirmed Infant HIV Infection | Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first | Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit (i.e., any visit after the Week 1 \[Day 6-14\] visit), confirmed by HIV NAT positivity of a second specimen drawn at a different time point. Analyses were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event. |
| Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies) | Measured at birth | Composite outcome |
| Antepartum Component: Number of Mothers With Obstetrical Complications | Measured through the Week 1 postpartum study visit | Complications included deaths, diagnoses, signs/symptoms, chemistry lab tests, or hematological lab tests, with grades of 3 (Severe) or worse. Obstetrical complications were those classified by the MedDra coding system as Pregnancy, puerperium and perinatal conditions, except if the condition was the death of the fetus: Abortions not specified as induced or spontaneous, Abortions spontaneous, or Stillbirth and foetal death. |
| Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Measured through the Week 1 postpartum study visit | These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery | Measured at 12 and 24 months post-delivery | Analyses (Kaplan-Meier probabilities) conducted for all individual infants (rather than M-I pair) |
| Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | Measured from birth through 104 weeks of age | For overall survival, failure was defined to be death. For HIV-free survival, failure was defined to be either death or developing HIV. The probability of living, or living without HIV infection, at 104 weeks was calculated by Kaplan-Meier estimation of the survival function. |
| Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Measured at the time of delivery | Analysis used the principle of intent to treat. |
| Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery | Measured through 24 months post-delivery | Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit, confirmed by HIV NAT positivity of a second specimen drawn at a different time point, or infant death. Analyses (Kaplan-Meier probabilities) were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event. |
| Maternal Health Component: Incidence of Death | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | Number of women who died during the maternal health component; that is, who had been randomized to either continue or discontinue ART after risk of HIV vertical transmission through breastfeeding was over. |
| Maternal Health Component: Incidence of AIDS-defining Illness | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses listed in Appendix IV. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group. |
| Maternal Health Component: Incidence of HIV/AIDS-related Events | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | HIV/AIDS-related event refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group. |
| Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | Cardiovascular or metabolic events of particular concern were included in this analysis. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Metabolic events considered were diabetes mellitus, lipodystrophy, or dyslipidemia. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy. |
| Maternal Health Component: Other Targeted Medical Conditions | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | Other (non-cardiologic) medical conditions of particular concern were included in this outcome. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Events included were metabolic events, hepatic events, renal events, infections such as pulmonary tuberculosis, malaria, or other serious bacterial infections, and others. |
| Maternal Health Component: Incidence of HIV/AIDS-related Event or Death | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | HIV/AIDS-related event refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group. |
| Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | HIV/AIDS-related event refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group. |
| Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | Particular events were targeted as those of particular concern. This outcome considered all such events: death, events defining WHO stages II, III, or IV, targeted cardiovascular adverse events, other targeted adverse events, or cancers which were not AIDS-defining. A complete list can be found in Appendix IV of the Protocol. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. |
| Maternal Health Component: Incidence of Tuberculosis | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | Incidence of tuberculosis. |
| Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | The maternal safety endpoints summarized include grade 2, 3 or 4 hematologies (hemoglobin (Hb), White Blood Cells (WBC), Absolute Neutrophil Count (ANC), platelet count), chemistries (Alanine Aminotransferase (ALT or SGPT), serum creatinine), and grade 3 or 4 signs and symptoms that occurred post-randomization. These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com). |
| Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event | From study entry until July 7, 2015, an average of 94 weeks of follow-up. | This outcome included AIDS-defining illnesses or cardiovascular, hepatic, or renal adverse events of particular concern which were evaluated as serious. Serious outcomes were both those defined as serious according to the International Conference on Harmonization (ICH) definition, or outcomes with grades equal to or worse than 3 (Severe). A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy. Hepatic events considered were cirrhosis and idiopathic sclerosing cholangitis. Renal events considered were renal insufficiency, acute or chronic. |
| Antepartum Component: Number of Infant HIV Infections | Measured at the birth (<= 3 days postpartum) visit | Detected by HIV NAT positivity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Postpartum Component: Rates and Patterns of Maternal and Infant Resistance to the Maternal and Infant ARV Regimens | Measured at the end of the 5-year study period | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study. |
| Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit (14 days - 9 weeks postpartum); Week 14 visit (10-19 weeks postpartum); Week 26 visit (20 to 31 weeks postpartum); Week 50 visit (44 to 55 weeks postpartum); and Week 74 visit (68 to 80 weeks postpartum). | Adherence is by maternal report; adherence through hair analysis is not included here. The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study. |
| Antepartum Component: Antepartum Change in HBV DNA Viral Load Between Week 8 and Baseline Levels (Using Log HBV DNA) Among Women With Detectable HBV DNA Viral Loads at Baseline and Other HBV Outcome Measures | Measured at Week 8 | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since changes in HBV DNA Viral Load was not a focus of the study. |
| Antepartum Component: Cost Effectiveness and Feasibility of the Trial ARV Regimens | Measured at the end of the 5-year study period | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since cost effectiveness was not a focus of the study. |
| Antepartum Component: Maternal and Infant Viral Resistance to the Maternal and Infant ARV Strategies | Measured at the end of the 5-year study period | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since viral resistance was not a focus of the study. |
| Antepartum Component: Adherence to the Maternal Antiretroviral (ARV) Regimen, as Measured by Maternal Report | Measured through the Week 1 postpartum study visit | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since adherence was not a focus of the study. |
| Maternal Health Component: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers | From study entry until July 7, 2015. | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since inflammation and thrombogenic markers were not a focus of the study. |
| Postpartum Component: Cost-effectiveness and Feasibility of the Study ARV Prophylaxis Regimens | Measured at the end of the 5-year study period | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study. |
| Postpartum Component: Pharmacokinetic Parameters of ARV Drugs Measured in Maternal Plasma, Hair, Breast Milk, and Infant Blood (Plasma or Dried Blood Spot) Samples Collected at Birth; Weeks 1, 6, 14, and 26; and Subsequent Visits During Breastfeeding | Measured through the last study visit during breastfeeding, or 18 months postpartum, whichever comes first | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since pharmacokinetics was not a focus of the study. |
| Postpartum Component: Functional Maternal Antibody and HIV-envelope Binding Responses in Breast Milk and Plasma, Until Cessation of Breastfeeding or 18 Months Postpartum, Whichever Comes First | Measured through the time of cessation of breastfeeding or 18 months postpartum, whichever comes first | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since functional maternal antibody and HIV-envelope binding responses were not a focus of the study. |
| Maternal Health Component: Cost-effectiveness | From study entry until July 7, 2015. | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study. |
| Maternal Health Component: Viral Resistance | From study entry until July 7, 2015. | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study. |
| Maternal Health Component: Self-reported Adherence | From study entry until July 7, 2015. | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study. |
| Maternal Health Component: Quality of Life | From study entry until July 7, 2015. | The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since quality of life was not a focus of the study. |
Countries
India, Malawi, South Africa, Tanzania, Uganda, Zambia, Zimbabwe
Participant flow
Recruitment details
From April 2011 to October 2014, pregnant or just-delivered women were recruited at medical centers in low-income countries.
Participants by arm
| Arm | Count |
|---|---|
| Antepartum Arm A Mothers received ZDV+sdNVP+TRV tail | 1,547 |
| Antepartum Arm B Mothers received Triple ARV (3TC-ZDV/LPV-RTV) | 1,545 |
| Antepartum Arm C Mothers received Triple ARV (FTC-TDF/LPV-RTV) | 445 |
| Late Presenters Registrational component to assess entry criteria for possible randomization in the Postpartum Component | 204 |
| Total | 3,741 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Protocol Version 2.0: 04/2011-09/2012 | Death | 6 | 9 | 1 | 2 |
| Protocol Version 2.0: 04/2011-09/2012 | Lost to Follow-up | 73 | 65 | 2 | 10 |
| Protocol Version 2.0: 04/2011-09/2012 | Other Reason | 3 | 5 | 1 | 0 |
| Protocol Version 2.0: 04/2011-09/2012 | Protocol Violation | 2 | 0 | 0 | 1 |
| Protocol Version 2.0: 04/2011-09/2012 | Site Closure | 15 | 19 | 1 | 0 |
| Protocol Version 2.0: 04/2011-09/2012 | Subject Unable to Get to Clinic | 44 | 61 | 2 | 5 |
| Protocol Version 2.0: 04/2011-09/2012 | Withdrawal by Subject | 89 | 82 | 2 | 10 |
| Protocol Version 3.0: 10/2012-10/2014 | Adverse Event | 1 | 0 | 0 | 0 |
| Protocol Version 3.0: 10/2012-10/2014 | Death | 3 | 5 | 1 | 1 |
| Protocol Version 3.0: 10/2012-10/2014 | Lost to Follow-up | 49 | 36 | 25 | 4 |
| Protocol Version 3.0: 10/2012-10/2014 | Other Reason | 5 | 8 | 1 | 3 |
| Protocol Version 3.0: 10/2012-10/2014 | Protocol Violation | 0 | 0 | 2 | 4 |
| Protocol Version 3.0: 10/2012-10/2014 | Site Closure | 12 | 11 | 2 | 0 |
| Protocol Version 3.0: 10/2012-10/2014 | Subject Unable to Get to Clinic | 28 | 26 | 15 | 5 |
| Protocol Version 3.0: 10/2012-10/2014 | Withdrawal by Subject | 54 | 52 | 31 | 3 |
Baseline characteristics
| Characteristic | Late Presenters | Antepartum Arm C | Antepartum Arm B | Antepartum Arm A | Total |
|---|---|---|---|---|---|
| Absolute Neutrophil Count at Baseline | 5680 cells/mm^3 | 3990 cells/mm^3 | 4209 cells/mm^3 | 4140 cells/mm^3 | 4220 cells/mm^3 |
| Age, Continuous | 26.8 years | 26.4 years | 26.6 years | 26.5 years | 26.5 years |
| ALT (SGPT) | 16.5 units/liter | 12 units/liter | 12 units/liter | 12 units/liter | 12 units/liter |
| BMI | 23.6 kg/m^2 | 26.3 kg/m^2 | 26.3 kg/m^2 | 25.9 kg/m^2 | 26 kg/m^2 |
| Calculated Creatinine Clearance (ml/min) > 100 - 120 ml/min | 31 Participants | 39 Participants | 108 Participants | 90 Participants | 268 Participants |
| Calculated Creatinine Clearance (ml/min) > 120 ml/min | 154 Participants | 397 Participants | 1401 Participants | 1424 Participants | 3376 Participants |
| Calculated Creatinine Clearance (ml/min) > 50 - 60 ml/min | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Calculated Creatinine Clearance (ml/min) <= 50 ml/min | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Calculated Creatinine Clearance (ml/min) > 60 - 80 ml/min | 2 Participants | 2 Participants | 5 Participants | 5 Participants | 14 Participants |
| Calculated Creatinine Clearance (ml/min) > 80 - 100 ml/min | 10 Participants | 6 Participants | 31 Participants | 27 Participants | 74 Participants |
| CD4 count at screening | 520 cells/mm^3 | 538 cells/mm^3 | 526 cells/mm^3 | 534 cells/mm^3 | 530 cells/mm^3 |
| Gestational age at study entry 14 - <28 weeks | 0 Participants | 264 Participants | 1008 Participants | 956 Participants | 2228 Participants |
| Gestational age at study entry <14 weeks | 0 Participants | 2 Participants | 8 Participants | 10 Participants | 20 Participants |
| Gestational age at study entry 28 - <34 weeks | 1 Participants | 116 Participants | 368 Participants | 418 Participants | 903 Participants |
| Gestational age at study entry 34 - < 37 weeks | 0 Participants | 45 Participants | 113 Participants | 117 Participants | 275 Participants |
| Gestational age at study entry >= 37 weeks | 9 Participants | 18 Participants | 47 Participants | 46 Participants | 120 Participants |
| Gestational age at study entry (weeks) | 38.6 weeks | 26 weeks | 25.2 weeks | 25.7 weeks | 25.6 weeks |
| Hemoglobin | 10.6 g/dl | 11 g/dl | 11.1 g/dl | 11 g/dl | 11 g/dl |
| HIV RNA level prior to randomization | 12140 copies/ml | 8393 copies/ml | 8002 copies/ml | 6409 copies/ml | 7409 copies/ml |
| Platelet count | 255000 cells/mm^3 | 242500 cells/mm^3 | 236000 cells/mm^3 | 238000 cells/mm^3 | 239000 cells/mm^3 |
| Race/Ethnicity, Customized Asian, Pacific Islander | 19 Participants | 1 Participants | 46 Participants | 47 Participants | 113 Participants |
| Race/Ethnicity, Customized Black Non-Hispanic | 183 Participants | 440 Participants | 1487 Participants | 1493 Participants | 3603 Participants |
| Race/Ethnicity, Customized Hispanic (Regardless of Race) | 2 Participants | 4 Participants | 12 Participants | 7 Participants | 25 Participants |
| Region of Enrollment India | 19 Participants | 0 Participants | 46 Participants | 46 Participants | 111 Participants |
| Region of Enrollment Malawi | 31 Participants | 155 Participants | 493 Participants | 489 Participants | 1168 Participants |
| Region of Enrollment South Africa | 27 Participants | 78 Participants | 510 Participants | 513 Participants | 1128 Participants |
| Region of Enrollment Tanzania | 0 Participants | 10 Participants | 24 Participants | 23 Participants | 57 Participants |
| Region of Enrollment Uganda | 9 Participants | 85 Participants | 205 Participants | 207 Participants | 506 Participants |
| Region of Enrollment Zambia | 2 Participants | 18 Participants | 31 Participants | 32 Participants | 83 Participants |
| Region of Enrollment Zimbabwe | 116 Participants | 99 Participants | 236 Participants | 237 Participants | 688 Participants |
| Serum Creatinine | 0.6 mg/dL | 0.5 mg/dL | 0.5 mg/dL | 0.5 mg/dL | 0.5 mg/dL |
| Sex: Female, Male Female | 204 Participants | 445 Participants | 1545 Participants | 1547 Participants | 3741 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| The Last ARV Regimen before Entry during the Current Pregnancy HAART including NNRTI | 7 Participants | 0 Participants | 1 Participants | 1 Participants | 9 Participants |
| The Last ARV Regimen before Entry during the Current Pregnancy No ARVs during the current pregnancy | 153 Participants | 317 Participants | 1200 Participants | 1203 Participants | 2873 Participants |
| The Last ARV Regimen before Entry during the Current Pregnancy One NRTI | 0 Participants | 125 Participants | 336 Participants | 326 Participants | 787 Participants |
| The Last ARV Regimen before Entry during the Current Pregnancy sdNVP | 33 Participants | 0 Participants | 2 Participants | 5 Participants | 40 Participants |
| The Last ARV Regimen before Entry during the Current Pregnancy sdNVP+ZDV | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| The Last ARV Regimen before Entry during the Current Pregnancy Two NRTIs | 10 Participants | 3 Participants | 5 Participants | 2 Participants | 20 Participants |
| The Most Complex ARV Regimen for Prior PMTCT HAART including NNRTI | 0 Participants | 2 Participants | 5 Participants | 7 Participants | 14 Participants |
| The Most Complex ARV Regimen for Prior PMTCT No ARVs for prior PMTCT/no prior pregnancy | 202 Participants | 422 Participants | 1442 Participants | 1456 Participants | 3522 Participants |
| The Most Complex ARV Regimen for Prior PMTCT One NRTI | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| The Most Complex ARV Regimen for Prior PMTCT One PI | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| The Most Complex ARV Regimen for Prior PMTCT sdNVP | 2 Participants | 15 Participants | 46 Participants | 41 Participants | 104 Participants |
| The Most Complex ARV Regimen for Prior PMTCT sdNVP+ZDV | 0 Participants | 6 Participants | 48 Participants | 33 Participants | 87 Participants |
| Viral Load at enrollment | 4.1 log10 copies/mL | 3.9 log10 copies/mL | 3.9 log10 copies/mL | 3.8 log10 copies/mL | 3.9 log10 copies/mL |
| WBC | 8660 (cells/mm^3) | 6840 (cells/mm^3) | 6900 (cells/mm^3) | 6800 (cells/mm^3) | 6900 (cells/mm^3) |
| Weight | 60.9 kg | 64.4 kg | 64.6 kg | 64 kg | 64 kg |
| WHO Clinical Staging of HIV/AIDS Clinical stage I | 165 Participants | 434 Participants | 1506 Participants | 1493 Participants | 3598 Participants |
| WHO Clinical Staging of HIV/AIDS Clinical stage II | 4 Participants | 11 Participants | 34 Participants | 50 Participants | 99 Participants |
| WHO Clinical Staging of HIV/AIDS Clinical stage III | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 1,547 | 14 / 1,545 | 2 / 445 | 3 / 204 | 59 / 1,500 | 46 / 1,478 | 27 / 429 | 5 / 204 |
| other Total, other adverse events | 1,413 / 1,547 | 1,414 / 1,545 | 388 / 445 | 169 / 204 | 1,406 / 1,500 | 1,388 / 1,478 | 403 / 429 | 170 / 204 |
| serious Total, serious adverse events | 267 / 1,547 | 276 / 1,545 | 69 / 445 | 10 / 204 | 296 / 1,500 | 287 / 1,478 | 113 / 429 | 20 / 204 |
Outcome results
Primary
Antepartum Component: Number of Confirmed Infant HIV Infections
Defined as HIV nucleic acid test (NAT) positivity of the specimen drawn at either the birth (Day 0-5) or Week 1 (Day 6-14) visit, confirmed by HIV NAT positivity of a second specimen collected at a different time point
Time frame: Measured at birth or Week 1 study visit
Population: Analysis includes data from periods 1 and 2. Analysis is among the live births with HIV test results summarized for the maternal-infant set (the worst outcome summarized for cases of multiple births). Analysis used the principle of intent to treat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Antepartum Arm A | Antepartum Component: Number of Confirmed Infant HIV Infections | 25 Participants |
| Antepartum Arm B | Antepartum Component: Number of Confirmed Infant HIV Infections | 7 Participants |
| Antepartum Arm C | Antepartum Component: Number of Confirmed Infant HIV Infections | 2 Participants |
Comparison: Arm B and Arm C were combined and compared to Arm A. This comparison was an a priori planned comparison.96.5% CI: [-2.1, -0.4]
Primary
Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies)
Composite outcome
Time frame: Measured at birth
Population: Includes mothers with confirmed infant birth outcome as live birth, stillbirth, or spontaneous abortion and outcome assessments. Multiple gestation pregnancies (twins and triplets) were summarized at the unique mother level. Analysis used the principle of intent to treat.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Antepartum Arm A | Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies) | Periods 1 and 2 | 389 Participants |
| Antepartum Arm A | Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies) | Period 2 | 91 Participants |
| Antepartum Arm B | Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies) | Periods 1 and 2 | 563 Participants |
| Antepartum Arm B | Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies) | Period 2 | 123 Participants |
| Antepartum Arm C | Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies) | Period 2 | 111 Participants |
Comparison: Periods 1 and 2p-value: <0.001Fisher Exact
Comparison: Period 2p-value: 0.04Fisher Exact
Comparison: Period 2p-value: 0.46Fisher Exact
Primary
Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).
Time frame: Measured through the Week 1 postpartum study visit
Population: Mothers with no safety data available after baseline were not included. Analysis used the principle of intent to treat.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Antepartum Arm A | Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Period 2 | 59 Participants |
| Antepartum Arm A | Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Periods 1 and 2 | 261 Participants |
| Antepartum Arm B | Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Periods 1 and 2 | 318 Participants |
| Antepartum Arm B | Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Period 2 | 61 Participants |
| Antepartum Arm C | Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | Period 2 | 60 Participants |
Comparison: Periods 1 and 2p-value: 0.008Fisher Exact
Comparison: Period 2p-value: 0.77Fisher Exact
Comparison: Period 2p-value: >0.99Fisher Exact
Primary
Antepartum Component: Number of Mothers With Obstetrical Complications
Complications included deaths, diagnoses, signs/symptoms, chemistry lab tests, or hematological lab tests, with grades of 3 (Severe) or worse. Obstetrical complications were those classified by the MedDra coding system as Pregnancy, puerperium and perinatal conditions, except if the condition was the death of the fetus: Abortions not specified as induced or spontaneous, Abortions spontaneous, or Stillbirth and foetal death.
Time frame: Measured through the Week 1 postpartum study visit
Population: Mothers who do not have any obstetrical complications information available after study entry are not included. Analysis used the principle of intent to treat.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Antepartum Arm A | Antepartum Component: Number of Mothers With Obstetrical Complications | Periods 1 and 2 | 89 Participants |
| Antepartum Arm A | Antepartum Component: Number of Mothers With Obstetrical Complications | Period 2 | 20 Participants |
| Antepartum Arm B | Antepartum Component: Number of Mothers With Obstetrical Complications | Periods 1 and 2 | 75 Participants |
| Antepartum Arm B | Antepartum Component: Number of Mothers With Obstetrical Complications | Period 2 | 12 Participants |
| Antepartum Arm C | Antepartum Component: Number of Mothers With Obstetrical Complications | Period 2 | 23 Participants |
Comparison: Periods 1 and 2p-value: 0.3Fisher Exact
Comparison: Period 2p-value: 0.64Fisher Exact
Comparison: Period 2p-value: 0.06Fisher Exact
Primary
Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death
AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses in Appendix IV of the protocol. These events were reviewed and confirmed by an Endpoint review group.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death | 0.24 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death | 0.49 New cases per 100 person-years |
p-value: 0.3795% CI: [0.14, 2.08]Log Rank
Primary
Postpartum Component: Incidence of Confirmed Infant HIV Infection
Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit (i.e., any visit after the Week 1 \[Day 6-14\] visit), confirmed by HIV NAT positivity of a second specimen drawn at a different time point. Analyses were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.
Time frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
Population: All Mother-Infant (M-I) pairs, except 1 M-I pair where infant was infected at date of randomization, were included in the analyses. 35 M-I pairs with no post-randomization HIV test results were included and censored at the date of randomization in the analyses. Analyses were intent to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Postpartum Component: Incidence of Confirmed Infant HIV Infection | 0.56 New cases per 100 person-years |
| Antepartum Arm B | Postpartum Component: Incidence of Confirmed Infant HIV Infection | 0.55 New cases per 100 person-years |
96% CI: [0.3, 3.1]
Primary
Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).
Time frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
Population: All mothers were included in the analyses. 15 mothers with no post-randomization data were included and censored at the date of randomization in the analyses. Analyses were intent to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | 14.4 New cases per 100 person-years |
| Antepartum Arm B | Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events | 14.1 New cases per 100 person-years |
p-value: 0.98Log Rank
Secondary
Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery
Analysis used the principle of intent to treat.
Time frame: Measured at the time of delivery
Population: Analysis includes only mothers with HIV RNA data at delivery. Analysis used the principle of intent to treat.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Antepartum Arm A | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Period 2 | HIV RNA < 400 copies/mL | 102 Participants |
| Antepartum Arm A | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Periods 1 and 2 | HIV RNA < 400 copies/mL | 415 Participants |
| Antepartum Arm A | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Period 2 | HIV RNA >= 400 copies/mL | 210 Participants |
| Antepartum Arm A | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Periods 1 and 2 | HIV RNA >= 400 copies/mL | 929 Participants |
| Antepartum Arm B | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Period 2 | HIV RNA < 400 copies/mL | 259 Participants |
| Antepartum Arm B | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Periods 1 and 2 | HIV RNA < 400 copies/mL | 1092 Participants |
| Antepartum Arm B | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Periods 1 and 2 | HIV RNA >= 400 copies/mL | 275 Participants |
| Antepartum Arm B | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Period 2 | HIV RNA >= 400 copies/mL | 62 Participants |
| Antepartum Arm C | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Period 2 | HIV RNA >= 400 copies/mL | 79 Participants |
| Antepartum Arm C | Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery | Period 2 | HIV RNA < 400 copies/mL | 225 Participants |
Secondary
Antepartum Component: Number of Infant HIV Infections
Detected by HIV NAT positivity
Time frame: Measured at the birth (<= 3 days postpartum) visit
Population: Analysis is among the live births with HIV test results summarized in the maternal-infant set (the worst outcome summarized for multiple births to the same mother). Analysis used the principle of intent to treat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Antepartum Arm A | Antepartum Component: Number of Infant HIV Infections | 22 Participants |
| Antepartum Arm B | Antepartum Component: Number of Infant HIV Infections | 4 Participants |
| Antepartum Arm C | Antepartum Component: Number of Infant HIV Infections | 2 Participants |
Secondary
Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component)
For overall survival, failure was defined to be death. For HIV-free survival, failure was defined to be either death or developing HIV. The probability of living, or living without HIV infection, at 104 weeks was calculated by Kaplan-Meier estimation of the survival function.
Time frame: Measured from birth through 104 weeks of age
Population: Infants in the antepartum component not excluded from analysis; only one infant was included per pregnancy, the one with the earliest failure time. The Periods 1\&2 group is infants born to mothers randomized in Arms A and B throughout the PROMISE study (both protocol versions). The period 2 group includes infants born to mothers randomized during the last protocol version only. Since Arm C was only available to all under the last protocol version, this enables unbiased comparison with Arm C.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antepartum Arm A | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | Overall survival, Periods 1 & 2 group (arms A & B only) | 0.959 Proportional probability |
| Antepartum Arm A | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | Overall survival, period 2 group | 0.951 Proportional probability |
| Antepartum Arm A | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | HIV-free survival, Periods 1&2 group (arms A&B only) | 0.937 Proportional probability |
| Antepartum Arm A | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | HIV-free survival, period 2 group | 0.936 Proportional probability |
| Antepartum Arm B | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | HIV-free survival, period 2 group | 0.940 Proportional probability |
| Antepartum Arm B | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | HIV-free survival, Periods 1&2 group (arms A&B only) | 0.947 Proportional probability |
| Antepartum Arm B | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | Overall survival, Periods 1 & 2 group (arms A & B only) | 0.967 Proportional probability |
| Antepartum Arm B | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | Overall survival, period 2 group | 0.982 Proportional probability |
| Antepartum Arm C | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | Overall survival, period 2 group | 0.942 Proportional probability |
| Antepartum Arm C | Antepartum Component: Probability of Overall and HIV-free Infant Survival Until 104 Weeks of Age, by Antepartum Arm (in Conjunction With Infants in the Postpartum Component) | HIV-free survival, period 2 group | 0.921 Proportional probability |
Comparison: Overall survivalp-value: 0.16Two-sided Z test
Comparison: Overall survival, period 2 groupp-value: 0.0156Two-sided Z test
Comparison: Overall survival, period 2 groupp-value: 0.31Two-sided Z test
Comparison: Overall survival, period 2 groupp-value: 0.0022Two-sided Z test
Comparison: HIV-free survivalp-value: 0.13Two-sided Z test
Comparison: HIV-free survival, period 2 groupp-value: 0.44Two-sided Z test
Comparison: HIV-free survival, period 2 groupp-value: 0.24Two-sided Z test
Comparison: HIV-free survival, group 2p-value: 0.26Two-sided Z test
Secondary
Maternal Health Component: Incidence of AIDS-defining Illness
AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses listed in Appendix IV. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of AIDS-defining Illness | 0.08 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of AIDS-defining Illness | 0.25 New cases per 100 person-years |
Secondary
Maternal Health Component: Incidence of Death
Number of women who died during the maternal health component; that is, who had been randomized to either continue or discontinue ART after risk of HIV vertical transmission through breastfeeding was over.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of Death | 0.24 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of Death | 0.43 New cases per 100 person-years |
Secondary
Maternal Health Component: Incidence of HIV/AIDS-related Event or Death
HIV/AIDS-related event refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of HIV/AIDS-related Event or Death | 1.30 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of HIV/AIDS-related Event or Death | 1.43 New cases per 100 person-years |
Secondary
Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events
HIV/AIDS-related event refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events | 3.47 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events | 5.61 New cases per 100 person-years |
Secondary
Maternal Health Component: Incidence of HIV/AIDS-related Events
HIV/AIDS-related event refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of HIV/AIDS-related Events | 1.14 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of HIV/AIDS-related Events | 1.24 New cases per 100 person-years |
Secondary
Maternal Health Component: Incidence of Tuberculosis
Incidence of tuberculosis.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence of Tuberculosis | 0.40 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence of Tuberculosis | 0.31 New cases per 100 person-years |
Secondary
Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events
Cardiovascular or metabolic events of particular concern were included in this analysis. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Metabolic events considered were diabetes mellitus, lipodystrophy, or dyslipidemia. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events | 2.9 events per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events | 5.7 events per 100 person-years |
Secondary
Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern
Particular events were targeted as those of particular concern. This outcome considered all such events: death, events defining WHO stages II, III, or IV, targeted cardiovascular adverse events, other targeted adverse events, or cancers which were not AIDS-defining. A complete list can be found in Appendix IV of the Protocol. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern | 9.0 events per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern | 14.0 events per 100 person-years |
Secondary
Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event
This outcome included AIDS-defining illnesses or cardiovascular, hepatic, or renal adverse events of particular concern which were evaluated as serious. Serious outcomes were both those defined as serious according to the International Conference on Harmonization (ICH) definition, or outcomes with grades equal to or worse than 3 (Severe). A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Cardiovascular events considered were hypertension, congestive heart failure, stroke, Transient Ischemia Event (TIA), pulmonary embolism, myocardial infarction (whether acute symptomatic or silent), coronary artery disease, deep vein thrombosis, peripheral vascular disease, or symptomatic HIV-associated cardiomyopathy. Hepatic events considered were cirrhosis and idiopathic sclerosing cholangitis. Renal events considered were renal insufficiency, acute or chronic.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event | 0.5 events per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event | 0.9 events per 100 person-years |
Secondary
Maternal Health Component: Other Targeted Medical Conditions
Other (non-cardiologic) medical conditions of particular concern were included in this outcome. A Poisson model with time to first event as an offset and an over-dispersion parameter was used to estimate incidence rates. Events included were metabolic events, hepatic events, renal events, infections such as pulmonary tuberculosis, malaria, or other serious bacterial infections, and others.
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Other Targeted Medical Conditions | 4.0 events per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Other Targeted Medical Conditions | 4.6 events per 100 person-years |
Secondary
Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results
The maternal safety endpoints summarized include grade 2, 3 or 4 hematologies (hemoglobin (Hb), White Blood Cells (WBC), Absolute Neutrophil Count (ANC), platelet count), chemistries (Alanine Aminotransferase (ALT or SGPT), serum creatinine), and grade 3 or 4 signs and symptoms that occurred post-randomization. These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).
Time frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Population: This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results | 15.3 New cases per 100 person-years |
| Antepartum Arm B | Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results | 13.9 New cases per 100 person-years |
Secondary
Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery
Analyses (Kaplan-Meier probabilities) conducted for all individual infants (rather than M-I pair)
Time frame: Measured at 12 and 24 months post-delivery
Population: All live-born infants were included in the analyses. 4 infants with no post-randomization data were included and censored at the date of randomization in the analyses. Analyses were intent to treat.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antepartum Arm A | Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery | 12 months post delivery | 0.988 Probability |
| Antepartum Arm A | Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery | 24 months post delivery | 0.978 Probability |
| Antepartum Arm B | Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery | 12 months post delivery | 0.989 Probability |
| Antepartum Arm B | Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery | 24 months post delivery | 0.987 Probability |
Secondary
Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery
Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit, confirmed by HIV NAT positivity of a second specimen drawn at a different time point, or infant death. Analyses (Kaplan-Meier probabilities) were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.
Time frame: Measured through 24 months post-delivery
Population: All M-I pairs, except 1 M-I pair where infant was infected at date of randomization, were included in the analyses. 3 M-I pairs with no post-randomization data were included and censored at the date of randomization. Analyses were intent to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antepartum Arm A | Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery | 0.971 Probability |
| Antepartum Arm B | Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery | 0.977 Probability |
Other Pre-specified
Antepartum Component: Adherence to the Maternal Antiretroviral (ARV) Regimen, as Measured by Maternal Report
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since adherence was not a focus of the study.
Time frame: Measured through the Week 1 postpartum study visit
Other Pre-specified
Antepartum Component: Antepartum Change in HBV DNA Viral Load Between Week 8 and Baseline Levels (Using Log HBV DNA) Among Women With Detectable HBV DNA Viral Loads at Baseline and Other HBV Outcome Measures
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since changes in HBV DNA Viral Load was not a focus of the study.
Time frame: Measured at Week 8
Other Pre-specified
Antepartum Component: Cost Effectiveness and Feasibility of the Trial ARV Regimens
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since cost effectiveness was not a focus of the study.
Time frame: Measured at the end of the 5-year study period
Other Pre-specified
Antepartum Component: Maternal and Infant Viral Resistance to the Maternal and Infant ARV Strategies
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome measure since viral resistance was not a focus of the study.
Time frame: Measured at the end of the 5-year study period
Other Pre-specified
Maternal Health Component: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since inflammation and thrombogenic markers were not a focus of the study.
Time frame: From study entry until July 7, 2015.
Other Pre-specified
Maternal Health Component: Cost-effectiveness
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study.
Time frame: From study entry until July 7, 2015.
Other Pre-specified
Maternal Health Component: Quality of Life
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since quality of life was not a focus of the study.
Time frame: From study entry until July 7, 2015.
Other Pre-specified
Maternal Health Component: Self-reported Adherence
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study.
Time frame: From study entry until July 7, 2015.
Other Pre-specified
Maternal Health Component: Viral Resistance
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study.
Time frame: From study entry until July 7, 2015.
Other Pre-specified
Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures
Adherence is by maternal report; adherence through hair analysis is not included here. The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since adherence was not a focus of the study.
Time frame: Week 6 visit (14 days - 9 weeks postpartum); Week 14 visit (10-19 weeks postpartum); Week 26 visit (20 to 31 weeks postpartum); Week 50 visit (44 to 55 weeks postpartum); and Week 74 visit (68 to 80 weeks postpartum).
Population: Women or infants in the postpartum component who had been included in the primary efficacy analysis (outcome measure #5 above), i.e., who had not yet reached the site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first, and whose adherence questionnaire was filled out.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Never missed a dose | 1003 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Missed dose over 1 month ago | 12 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Missed dose 2-4 weeks ago | 17 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Missed dose within last 2 weeks | 140 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Never missed a dose | 956 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Missed dose over 1 month ago | 20 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Missed dose 2-4 weeks ago | 35 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Missed dose within last 2 weeks | 112 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Never missed a dose | 888 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Missed dose over 1 month ago | 48 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Missed dose 2-4 weeks ago | 31 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Missed dose within last 2 weeks | 103 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Never missed a dose | 716 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Missed dose over 1 month ago | 37 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Missed dose 2-4 weeks ago | 34 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Missed dose within last 2 weeks | 64 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Never missed a dose | 311 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Missed dose over 1 month ago | 15 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Missed dose 2-4 weeks ago | 17 Participants |
| Antepartum Arm A | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Missed dose within last 2 weeks | 34 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Missed dose over 1 month ago | 2 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Never missed a dose | 1104 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Missed dose 2-4 weeks ago | 8 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Missed dose over 1 month ago | 0 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Missed dose within last 2 weeks | 30 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Missed dose 2-4 weeks ago | 4 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Missed dose within last 2 weeks | 47 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 6 visit | Missed dose within last 2 weeks | 74 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Missed dose within last 2 weeks | 9 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Never missed a dose | 1081 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Never missed a dose | 841 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Missed dose over 1 month ago | 0 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Never missed a dose | 377 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Missed dose 2-4 weeks ago | 9 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Missed dose over 1 month ago | 9 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 14 visit | Missed dose within last 2 weeks | 50 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 74 visit | Missed dose 2-4 weeks ago | 1 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Never missed a dose | 1035 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 50 visit | Missed dose 2-4 weeks ago | 7 Participants |
| Antepartum Arm B | Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures | Week 26 visit | Missed dose over 1 month ago | 1 Participants |
Other Pre-specified
Postpartum Component: Cost-effectiveness and Feasibility of the Study ARV Prophylaxis Regimens
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since cost-effectiveness was not a focus of the study.
Time frame: Measured at the end of the 5-year study period
Other Pre-specified
Postpartum Component: Functional Maternal Antibody and HIV-envelope Binding Responses in Breast Milk and Plasma, Until Cessation of Breastfeeding or 18 Months Postpartum, Whichever Comes First
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since functional maternal antibody and HIV-envelope binding responses were not a focus of the study.
Time frame: Measured through the time of cessation of breastfeeding or 18 months postpartum, whichever comes first
Other Pre-specified
Postpartum Component: Pharmacokinetic Parameters of ARV Drugs Measured in Maternal Plasma, Hair, Breast Milk, and Infant Blood (Plasma or Dried Blood Spot) Samples Collected at Birth; Weeks 1, 6, 14, and 26; and Subsequent Visits During Breastfeeding
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since pharmacokinetics was not a focus of the study.
Time frame: Measured through the last study visit during breastfeeding, or 18 months postpartum, whichever comes first
Other Pre-specified
Postpartum Component: Rates and Patterns of Maternal and Infant Resistance to the Maternal and Infant ARV Regimens
The protocol did not distinguish between outcomes essential to the primary publication and outcomes for subsequent publications of lesser priority. This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome since viral resistance was not a focus of the study.
Time frame: Measured at the end of the 5-year study period