Phase 3
N=1,870
Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT01061151 ↗Enrolled (actual)
1,870
Serious AEs
18.2%
Results posted
Feb 2018
Primary outcome: Primary: Antepartum Component: Number of Confirmed Infant HIV Infections — 25; 7; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Zidovudine (ZDV) (Drug); Nevirapine (NVP): Antepartum Mothers (Drug); Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail (Drug); Lamivudine-Zidovudine (3TC-ZDV) (Drug); Lopinavir-ritonavir (LPV-RTV) (Drug); Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) (Drug); Nevirapine (NVP): Infant short-course (Drug); Nevirapine (NVP): Infant extended (Drug); No Intervention (Other); Discontinue triple ARVs (Other); Continue triple ARVs (Other)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Sep 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Antepartum Component: Number of Confirmed Infant HIV Infections |
25; 7; 2 | — |
| PRIMARY Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events |
261; 318; 59; 61; 60 | 0.008 sig |
| PRIMARY Antepartum Component: Number of Mothers With Obstetrical Complications |
89; 75; 20; 12; 23 | 0.30 |
| 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) |
389; 563; 91; 123; 111 | <0.001 sig |
| PRIMARY Postpartum Component: Incidence of Confirmed Infant HIV Infection |
0.56; 0.55 | — |
| PRIMARY Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events |
14.4; 14.1 | 0.98 |
| PRIMARY Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death |
0.24; 0.49 | 0.37 |
| SECONDARY Antepartum Component: Number of Infant HIV Infections |
22; 4; 2 | — |
| 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) |
0.959; 0.967; 0.951; 0.982; 0.942; 0.937 | 0.16 |
| SECONDARY Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery |
415; 1092; 929; 275; 102; 259 | — |
| SECONDARY Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery |
0.971; 0.977 | — |
| SECONDARY Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery |
0.988; 0.989; 0.978; 0.987 | — |
| SECONDARY Maternal Health Component: Incidence of Death |
0.24; 0.43 | — |
| SECONDARY Maternal Health Component: Incidence of AIDS-defining Illness |
0.08; 0.25 | — |
| SECONDARY Maternal Health Component: Incidence of HIV/AIDS-related Events |
1.14; 1.24 | — |
| SECONDARY Maternal Health Component: Incidence Rate of Cardiovascular or Other Metabolic Events |
2.9; 5.7 | — |
| SECONDARY Maternal Health Component: Other Targeted Medical Conditions |
4.0; 4.6 | — |
| SECONDARY Maternal Health Component: Incidence of HIV/AIDS-related Event or Death |
1.30; 1.43 | — |
| SECONDARY Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events |
3.47; 5.61 | — |
| SECONDARY Maternal Health Component: Incidence Rate of Death or Any Condition of Particular Concern |
9.0; 14.0 | — |
| SECONDARY Maternal Health Component: Incidence of Tuberculosis |
0.40; 0.31 | — |
| 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 |
15.3; 13.9 | — |
| SECONDARY Maternal Health Component: Incidence Rate of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event |
0.5; 0.9 | — |
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.
Eligibility 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:
- Hemoglobin greater than or equal to 7.5 g/dL
- White blood cell count (WBC) greater than or equal to 1,500 cells/mm^3
- Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
- Platelets greater than or equal to 50,000 cells/mm^3
- Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal (ULN)
- 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 tim
Data sourced from ClinicalTrials.gov (NCT01061151). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.