Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries

• Register: ClinicalTrials.gov
• Last refreshed on: 21 February 2022
• Main ID: NCT01061151
• Date of registration: 01/02/2010
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries PROMISE
• Scientific title: Breastfeeding Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere)
• Date of first enrolment: March 1, 2011
• Target sample size: 3747
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01061151
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Double (Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

India, Malawi, South Africa, Tanzania, Uganda, Zambia, Zimbabwe

Contacts

• Name: Mary Glenn Fowler, MD, MPH
• Affiliation: Johns Hopkins Medical Institute, Makerere U.-JHU Research Collaboration

Key inclusion & exclusion 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 Exclusion Criteria:

- Participation in PROMISE in prior pregnancy

- Ingestion of any antiretroviral regimen during current pregnancy (including for solely
for PMTCT), according to self report and available medical records (Note: Use of ARVs
provided as standard of care for PMTCT during labor/delivery or postpartum prior to
Late Presenter registration is not exclusionary.)

- If known: CD4 count < 350 cells/mm3 or below the country-specific threshold for
initiation of treatment, if that threshold is > 350 cells/mm3, on specimen obtained
within 30 days prior to study entry (result not required prior to registration)

- Requires triple ARV therapy (HAART) for own health according to local standard
guidelines

- WHO Stage 4 disease

- Prior receipt of HAART for maternal treatment indications (e.g., CD4 < 350 cells/mm3
or clinical indications); however, could have received ARVs for the sole purpose of
PMTCT in previous pregnancies. (Prior PMTCT regimens could have included a triple ARV
regimen, ZDV, 3TCZDV and/or sdNVP for PMTCT, as well as use of a short dual NRTI
"tail" to reduce risk of NVP resistance.)

- Current or history of TB disease (positive PPD without TB disease is not exclusionary)

- Known positive infant HIV nucleic acid test (NAT) result (result not required prior to
registration)

- Fetal demise or early neonatal death (prior to enrollment/registration)

- Fetus detected with serious congenital malformation (ultrasound not required to rule
out this condition)

- Li


Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: Lopinavir-ritonavir (LPV-RTV)

Drug: Nevirapine (NVP): Infant short-course

Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Drug: Nevirapine (NVP): Antepartum Mothers

Other: Continue triple ARVs

Other: Discontinue triple ARVs

Other: No Intervention

Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail

Drug: Nevirapine (NVP): Infant extended

Drug: Lamivudine-Zidovudine (3TC-ZDV)

Drug: Zidovudine (ZDV)

Primary Outcome(s)

Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Postpartum Component: Incidence of Confirmed Infant HIV Infection [Time Frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first]

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) [Time Frame: Measured at birth]

Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events [Time Frame: Measured through the Week 1 postpartum study visit]

Antepartum Component: Number of Confirmed Infant HIV Infections [Time Frame: Measured at birth or Week 1 study visit]

Antepartum Component: Number of Mothers With Obstetrical Complications [Time Frame: Measured through the Week 1 postpartum study visit]

Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events [Time Frame: Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first]

Secondary Outcome(s)

Maternal Health Component: Incidence of Death [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery [Time Frame: Measured at 12 and 24 months post-delivery]

Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery [Time Frame: Measured through 24 months post-delivery]

Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery [Time Frame: Measured at the time of delivery]

Maternal Health Component: Incidence of HIV/AIDS-related Event or Death [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Other Targeted Medical Conditions [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

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) [Time Frame: Measured from birth through 104 weeks of age]

Antepartum Component: Number of Infant HIV Infections [Time Frame: Measured at the birth (<= 3 days postpartum) visit]

Maternal Health Component: Incidence of AIDS-defining Illness [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Incidence of HIV/AIDS-related Events [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Maternal Health Component: Incidence of Tuberculosis [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

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 [Time Frame: From study entry until July 7, 2015, an average of 94 weeks of follow-up.]

Secondary ID(s)

IMPAACT 1077BF

1077BF (PROMISE)

10777

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/02/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01061151