Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission

NCT01618305 | Completed Phase 4 Results DMC

• 5 other identifiers: P108110770NICHD P1081HHSN2752018000011.UM1AI068616
• Study Type: interventional
• Target: 408
• Locations: 7 countries
• Sites: 19

Brief Summary

HIV-infected pregnant women who begin taking antiretroviral (ARV) medications in the late stages of pregnancy need an effective medication regimen to reduce the risk of transmitting HIV to their children. This study examined the virologic response, safety, and tolerability of two different ARV medication regimens in HIV-infected pregnant women who were between 20 and 36 weeks pregnant when they entered the study.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (4)

• Proportion of Women With Plasma HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery

  If there was no viral load measurement at the delivery visit, the last viral load within three weeks prior to delivery was considered.

  Measured at participants' delivery visit (or last visit within three weeks prior to delivery)

• Proportion of Participants Who Discontinued Randomized Study Drug Prior to Labor and Delivery.

  Only women who initiated (i.e. received at least one dose of) their randomized treatment were eligible for this outcome measure. Women were considered to have discontinued study drug if they stopped receiving efavirenz or raltegravir (whichever was assigned) prior to labor and delivery for any reason, including loss to follow-up.

  Measured from entry through participants' delivery visit (approximately 36 to 40 weeks gestation)

• Proportion of Women Who Experienced at Least One New Adverse Event of Greater Than or Equal to Grade 3 as Defined in the Division of AIDS (DAIDS) Toxicity Table

  "New" adverse events were those with an onset date on or after randomization. Adverse events present at baseline would only be considered "New" if they increased in grade on or after randomization. All women who received at least one dose of study drug were eligible for this analysis.

  Measured from entry through participants' last study visit, approximately 24 weeks after delivery

• Proportion of Infants Who Experienced at Least One Adverse Event of Greater Than or Equal to Grade 3.

  All infants who were live births on study were eligible for this analysis. Adverse event grades were defined based on the DAIDS toxicity table.

  Measured from birth through infants' last study visit, approximately 24 weeks after delivery

Secondary Outcomes (14)

• Proportion of Women Who Achieved HIV-1 RNA Virologic Suppression Below the Lower Limit of Quantification of the Assay at Delivery

  Measured at participants' delivery visit (or last visit within three weeks prior to delivery)

• Proportion of Women With 1) Successful Viral Load (Plasma HIV-1 RNA VL) Decrease From Entry to Week 2 and VL Less Than 1,000 Copies/ml at All Time Points After 4 Weeks on Study Drugs, Until Delivery; and 2) Who Remain on the Assigned Study Regimen

  Measured from entry through delivery (approximately 36 to 40 weeks gestation).

• Log10 Change in Viral Load From Entry to Each Time Point Prior to Delivery

  Measured at antepartum Weeks 1, 2, 4, 6, 8, 10, 12, 14, and 16.

• Proportion of Women With HIV-1 RNA Plasma Viral Load Less Than 200 Copies/mL at Weeks 4 and 6 From Treatment Initiation

  Measured at Weeks 4 and 6 from first dose of randomized treatment, prior to delivery

• Proportion of Women With HIV-1 RNA Vaginal Viral Load Less Than 1200 Copies/mL at Weeks 4 and 6 From Treatment Initiation

  Measured at Weeks 4 and 6 from first dose of randomized treatment, prior to delivery

Study Arms (4)

Arm A (Women)

EXPERIMENTAL

Pregnant women received ZDV/3TC + EFV

Drug: Lamivudine/zidovudine; Drug: Efavirenz

Arm B (Women)

EXPERIMENTAL

Pregnant women received ZDV/3TC + RAL

Drug: Lamivudine/zidovudine; Drug: Raltegravir

Arm A (Infants)

NO INTERVENTION

Infants born to women in Arm A; infants received no study intervention.

Arm B (Infants)

NO INTERVENTION

Infants born to women in Arm B; infants received no study intervention.

Interventions

Lamivudine/zidovudine DRUG

Participants received one lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet twice a day from entry through delivery\*. \* Participants may have received a locally supplied nucleoside reverse transcriptase inhibitor (NRTI) backbone in place of lamivudine/zidovudine with permission of the protocol team obtained prior to randomization.

Also known as: ZDV/3TC

Arm A (Women); Arm B (Women)

Efavirenz DRUG

Participants received one 600 mg tablet of efavirenz each night from entry through delivery.

Also known as: EFV

Arm A (Women)

Raltegravir DRUG

Participants received one 400 mg raltegravir tablet twice a day from entry through delivery.

Also known as: RAL

Arm B (Women)

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Naive to antiretroviral therapy (ART) or have received ART with short course zidovudine (maximum of 8 weeks) for prevention of mother-to-child transmission in previous pregnancies
• Willing and able to sign informed consent. Participant must be of an age to provide legal informed consent as defined by the country in which the participant resides. If not, the informed consent must be signed by a legal guardian/parent, as per country guidelines.
• Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum, or plasma. Documentation may be abstracted from medical records to satisfy these criteria for infection. More information on this criterion can be found in the protocol.
• Viable pregnancy with gestational age of greater than or equal to 20 weeks to less than or equal to 36 weeks based upon menstrual history and/or ultrasound. Note: If menstrual history is unknown or if there is a discrepancy between menstrual history and ultrasound, determination of gestational age should be based upon best available methodology at each site.
• Intends to continue pregnancy
• Willingness and intent to deliver at the participating clinical site and to be followed for the duration of the study at the site or associated outpatient facility
• Willing to comply with the study regimen
• Agrees to use two reliable methods of contraception after delivery if randomized to the efavirenz arm and is sexually active. A barrier method of contraception (condoms, diaphragm, or cervical cap) together with another reliable form of contraception must be used for 4 weeks after stopping efavirenz.

You may not qualify if:

• Active labor defined as onset of regular contractions or cervical dilatation greater than 2 cm
• Use of ART during current pregnancy
• Chemotherapy for active malignancy
• Serious active opportunistic infection and/or serious bacterial infection including active tuberculosis (TB) or unstable or severe medical condition within 14 days of study entry
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
• Vomiting or inability to swallow medications due to an active, pre-existing condition that prevents adequate swallowing and absorption of study medication
• Known allergy/sensitivity to any study drugs or their formulations or sulfonamide allergy
• The following laboratory values (within 30 days of enrollment):
• Hemoglobin greater than or equal to Grade 3
• Absolute neutrophil count greater than or equal to Grade 2
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to Grade 2
• Serum creatinine greater than or equal to Grade 1
• Platelet count greater than or equal to Grade 3
• Evidence of pre-eclampsia (such as persistent diastolic blood pressure greater than 90 mm Hg)

Sponsors & Collaborators

• Westat: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (19)

South Flordia Childrens Diagnostic & Treatment Center

Fort Lauderdale, Florida, 33316, United States

Location

Tulane University

New Orleans, Louisiana, 70118, United States

Location

St Jude's Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Hosp. General de Agudos Buenos Aires Argentina NICHD CRS

Ciudad de Buenos Aires, Buenos Aires, C1221ADC, Argentina

Location

Fundacion Huesped - Hospital Juan A Fernandez

Buenos Aires, Argentina

Location

SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, Minas Gerais, 30.130-100, Brazil

Location

Univ. Caxias do Sul Brazil NICHD CRS

Caxias do Sul, Rio Grande do Sul, 95070-560, Brazil

Location

Hospital Nossa Senhora da Conceicao NICHD CRS

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, 20221-903, Brazil

Location

Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS

Rio de Janeiro, 21941-612, Brazil

Location

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, 26030, Brazil

Location

Univ. of Sao Paulo Brazil NICHD CRS

São Paulo, 14049-900, Brazil

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Perinatal HIV Research Unit-Chris Hani Baragwanath Hospital

Soweto, South Africa

Location

Kilimanjaro Christian Medical Centre (KCMC)

Moshi, Tanzania

Location

Siriraj Hospital ,Mahidol University NICHD CRS

Bangkok, Bangkoknoi, 10700, Thailand

Location

Bhumibol Adulyadej Hospital

Bangkok, 10220, Thailand

Location

Chiangrai Prachanukroh Hospital NICHD CRS

Chiang Mai, 50100, Thailand

Location

Related Publications (1)

• Joao EC, Morrison RL, Shapiro DE, Chakhtoura N, Gouvea MIS, de Lourdes B Teixeira M, Fuller TL, Mmbaga BT, Ngocho JS, Njau BN, Violari A, Mathiba R, Essack Z, Pilotto JHS, Moreira LF, Rolon MJ, Cahn P, Prommas S, Cressey TR, Chokephaibulkit K, Werarak P, Laimon L, Hennessy R, Frenkel LM, Anthony P, Best BM, Siberry GK, Mirochnick M. Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial. Lancet HIV. 2020 May;7(5):e322-e331. doi: 10.1016/S2352-3018(20)30038-2.

  PMID: 32386720 DERIVED

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014 (Corrected to Version 2.1, July 2017).
• The Division of AIDS Manual for the Expedited Reporting of Adverse Events, Version 2.0, January 2010.

MeSH Terms

Conditions

HIV Infections

Interventions

lamivudine, zidovudine drug combination; efavirenz; Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Lauren Laimon, Project Manager
• Organization: Westat

laurenlaimon@westat.com

240-453-2987

Study Officials

• Esau Joao, M.D.

  Hospital Federal dos Servidores do Estado - RJ

  STUDY CHAIR

• Mark Mirochnick, M.D.

  Boston Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 13, 2012
• Study Start: September 5, 2013
• Primary Completion: December 11, 2018
• Study Completion: December 11, 2018
• Last Updated: January 30, 2020
• Results First Posted: December 26, 2019

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months following publication and available throughout period of funding of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) by NIH.
• Access Criteria: With whom? Researchers whose proposed use of the data is approved by the NICHD Data and Specimen Hub (DASH) Data Access Committee as scientifically and ethically appropriate and does not conflict with constraints or informed consent limitations. For what types of analyses? To achieve aims in the approved proposal. By what mechanism will data be made available? To gain access, data requestors will need to create a free NICHD DASH account, submit a data access proposal, and if approved, sign a data access agreement. Information regarding creating a NICHD DASH account and accessing data may be found at https://dash.nichd.nih.gov/

Locations

BR (7); AR (2); PR (1); TA (1); TH (3); ZA (1); US (4)