IMPAACT 1077HS: Examining Benefits of HAART Continuation in Postpartum Women

NCT ID: NCT00955968

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1653 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-01
• Study Completion Date: 2016-08-31

Brief Summary

This study was a randomized strategy trial conducted among women who received highly active antiretroviral therapy (HAART) during pregnancy for purposes of prevention of mother-to-child transmission (PMTCT) of HIV but did not otherwise meet criteria to initiate HAART for their own health. The study was designed to determine whether continuation of HAART after delivery or other pregnancy outcome reduced morbidity and mortality compared to discontinuation and re-initiation of HAART when protocol specified criteria were met.

Detailed Description

This randomized strategy trial addressed therapeutic questions for women from regions where antepartum HAART for PMTCT (for all CD4+ cell counts) and postpartum formula feeding is standard of care, and who also had both a pre-HAART CD4+ cell count >400 cells/mm^3 and a screening (on-HAART) CD4+ cell count > 400 cells/mm^3. For these women, the objectives related to the relative efficacy and safety of continuing HAART (when it is no longer used for PMTCT) versus discontinuing HAART.

Potential participants were identified/recruited and consented during pregnancy or after delivery or other pregnancy outcome. Study-specific screening was initiated in the third trimester or after pregnancy outcome. Women who were screened for the study were counseled to continue their HAART until they were randomized.

Randomization would occur within 0-42 days after pregnancy outcome. Women who did not carry their pregnancy to the third trimester but otherwise meet study eligibility criteria could be enrolled.

Participants were randomized to one of the two study arms:

Arm A: Continuation of HAART Arm B: Discontinuation of HAART and resume HAART when protocol-specified criteria were met

Participants were to be followed until 84 weeks after the last participant was randomized.

Key evaluations were conducted at Screening, Entry, post entry visits were scheduled to take place 4 weeks after entry, 12 weeks after entry, and every 12 weeks thereafter. Key evaluations included physical examinations, clinical assessments, and blood collection.

On 7 July 2015, the study sites received formal communications regarding the results of the Strategic Timing of Antiretroviral Treatment (START) study and associated changes were implemented to the 1077HS study in response to these results. All sites were instructed that all women in the 1077HS study were to be informed of the START study results and that antiretroviral therapy (ART) was recommended for all women based on the START study results.

Conditions

HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continue HAART

Continue receiving HAART within 0-42 days after delivery or other pregnancy outcome.

Group Type: EXPERIMENTAL

Highly active antiretroviral therapy (HAART)

Intervention Type: DRUG

A combination of three or more HIV medications belonging to two or more drug classes.

The preferred study-supplied HAART regimen was lopinavir/ritonavir (LPV/RTV) plus fixed dose combination tenofovir/emtricitabine (TDF/FTC). Additional ARVs provided for use in this study included fixed dose combination lamivudine/zidovudine (3TC/ZDV), lamivudine (3TC), zidovudine (ZDV), tenofovir (TDF), fixed dose combination tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV), didanosine (ddI), atazanavir (ATV), raltegravir (RAL), and ritonavir (RTV). While LPV/RTV plus TDF/FTC was the preferred study-supplied regimen, the study clinicians in conjunction with participants would determine the optimal drug combination for each participant.

Stop HAART

Stop receiving HAART within 0-42 days after delivery or other pregnancy outcome and resume HAART when protocol specified criteria were met.

Group Type: ACTIVE_COMPARATOR

Highly active antiretroviral therapy (HAART)

Intervention Type: DRUG

A combination of three or more HIV medications belonging to two or more drug classes.

The preferred study-supplied HAART regimen was lopinavir/ritonavir (LPV/RTV) plus fixed dose combination tenofovir/emtricitabine (TDF/FTC). Additional ARVs provided for use in this study included fixed dose combination lamivudine/zidovudine (3TC/ZDV), lamivudine (3TC), zidovudine (ZDV), tenofovir (TDF), fixed dose combination tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV), didanosine (ddI), atazanavir (ATV), raltegravir (RAL), and ritonavir (RTV). While LPV/RTV plus TDF/FTC was the preferred study-supplied regimen, the study clinicians in conjunction with participants would determine the optimal drug combination for each participant.

Interventions

Highly active antiretroviral therapy (HAART)

A combination of three or more HIV medications belonging to two or more drug classes.

The preferred study-supplied HAART regimen was lopinavir/ritonavir (LPV/RTV) plus fixed dose combination tenofovir/emtricitabine (TDF/FTC). Additional ARVs provided for use in this study included fixed dose combination lamivudine/zidovudine (3TC/ZDV), lamivudine (3TC), zidovudine (ZDV), tenofovir (TDF), fixed dose combination tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV), didanosine (ddI), atazanavir (ATV), raltegravir (RAL), and ritonavir (RTV). While LPV/RTV plus TDF/FTC was the preferred study-supplied regimen, the study clinicians in conjunction with participants would determine the optimal drug combination for each participant.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women age ≥ 18 years or who had attained the minimum age of independent consent, as defined by the local Institutional Review Board (IRB), and were willing and able to provide written informed consent Additionally, at sites with IRB approval to enroll younger participants, women age 16-17 years who were willing and able to provide written assent and whose parent or legal guardian was willing and able to provide written informed consent
• Confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry, using protocol-specified tests (see protocol for more details)
• Documentation of hepatitis B surface antibody (HBsAb) status and hepatitis B surface antigen (HBsAg) status (if antibody was negative) within 12 months prior to study entry
• Within 0-42 days after pregnancy outcome
• Antiretroviral treatment naïve, defined as < 14 days of one or more antiretroviral agents, prior to therapy initiated during current pregnancy
• Receipt of at least four weeks of HAART prior to study entry, at least two weeks of which must have been prior to pregnancy outcome (up to seven consecutive days of missed therapy is permitted)
• CD4+ cell count ≥ 400 cells/mm^3 on a specimen obtained within 120 days prior to initiation of HAART for current pregnancy
• CD4+ cell count ≥ 400 cells/mm^3 on a specimen obtained on HAART and within 45 days prior to study entry
• The following laboratory values on a specimen obtained within 45 days prior to study entry:

• Absolute neutrophil count ≥ 750/mm^3
• Hemoglobin ≥ 7.0 g/dL
• Platelet count ≥ 50,000/mm^3
• AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN
• Estimated creatinine clearance of ≥ 60mL/min within 45 days prior to entry using the Cockcroft-Gault formula
• Intent to remain in current geographical area of residence for the duration of the study
• Willingness to attend study visits as required by the study

Exclusion Criteria

• Previous participation in PROMISE (P1077BF - NCT01061151)
• Clinical indication for HAART including any World Health Organization (WHO) Clinical Stage 3 or 4 condition, prior or current tuberculosis disease (a positive (Purified protein Derivative) PPD test alone was not considered exclusionary), and/or any other clinical indication per country-specific treatment guidelines
• Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
• Social or other circumstances which, in the opinion of the site investigator, would hinder long-term follow up
• Use of any prohibited medications within 14 days prior to study entry (refer to the study MOP for a list of prohibited medications)
• Current compulsory detention (involuntary incarceration) in a correctional facility, prison, or jail for legal reasons or compulsory detention in a medical facility for treatment of either a psychiatric or physical (e.g., infectious disease) illness
• Currently breastfeeding or planning to breastfeed
• Current documented conduction heart defect (specialized assessments to rule out this condition were not required; a heart murmur alone and/or type 1 second-degree atrioventricular block (also known as Mobitz I or Wenckebach) was not considered exclusionary)
• Known evidence of HBV DNA levels >2000 IU/mL (approximately 10,000 copies/mL) in the presence of elevated (grade 1 and higher) ALT (HBV DNA testing was not required for study screening or enrollment but was considered to determine whether treatment for HBV was indicated)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith S. Currier, MD, MS

Role: STUDY_CHAIR

University of California, Los Angeles

Locations

University of Southern California MCA Center (5048)

Alhambra, California, United States

David Geffen School of Medicine at UCLA (5112)

Los Angeles, California, United States

UCSD Mother-Child-Adolescent HIV Program (4601)

San Diego, California, United States

Harbor (UCLA) Medical Center (5045)

Torrance, California, United States

University of Colorado (5052)

Aurora, Colorado, United States

Howard University (5044)

Washington D.C., District of Columbia, United States

Georgetown University (1008)

Washington D.C., District of Columbia, United States

Washington Hospital Center (5023)

Washington D.C., District of Columbia, United States

Children's Diagnostic and Treatment Center (5055)

Fort Lauderdale, Florida, United States

University of Florida at Jacksonville (5051)

Jacksonville, Florida, United States

University of Miami Pediatric/Perinatal Clinical Research Site (4201)

Miami, Florida, United States

University of South Florida at Tampa (5018)

Tampa, Florida, United States

Ann & Robert H Lurie Children's Hospital of Chicago (4001)

Chicago, Illinois, United States

Tulane University (5095)

New Orleans, Louisiana, United States

Johns Hopkins University School of Medicine (5092)

Baltimore, Maryland, United States

Boston Medical Center (5011)

Boston, Massachusetts, United States

Wayne State University/Children's Hospital of Michigan (5041)

Detroit, Michigan, United States

Metropolitan Hospital (5003)

New York, New York, United States

SUNY Stony Brook University Medical Center (5040)

Stony Brook, New York, United States

Bronx-Lebanon Hospital Center (5114)

The Bronx, New York, United States

Jacobi Medical Center (5013)

The Bronx, New York, United States

Duke University Medical Center (4701)

Durham, North Carolina, United States

Pitt CRS (1001)

Pittsburgh, Pennsylvania, United States

St Jude Children's Research Hospital (6501)

Memphis, Tennessee, United States

Baylor College of Medicine Texas Children's Hospital (3801)

Houston, Texas, United States

Seattle Children's Hospital (5017)

Seattle, Washington, United States

Hospital General de Agudos (5082)

Buenos Aires, , Argentina

Gaborone Prevention/Treatment Clinical Research Site (12701)

Gaborone, , Botswana

Molepolole Prevention/Treatment Clinical Research Site (12702)

Gaborone, , Botswana

School of Medicine, University of Minas Gerais - FUNDEP (5073)

Belo Horizonte, , Brazil

University Caxias do Sul (5084)

Caxias do Sul, , Brazil

Hospital Nossa Senhora da Conceicao (5117)

Porto Alegre, , Brazil

Hospital Santa Casa (5098)

Porto Alegre, , Brazil

Hospital dos Servidores do Estado (5072)

Rio de Janeiro, , Brazil

Hospital Geral De Nova Igaucu (5097)

Rio de Janeiro, , Brazil

Instituto de Puericultura E Pediatria Martagao Geseira - FUJB (5071)

Rio de Janeiro, , Brazil

Ribeirao Preto Medical School, University of Sao Paulo (5074)

São Paulo, , Brazil

Guangxi Center for HIV/AIDS Prevention and Control (30274)

Nanning, Guangxi, China

Les Centres GHESKIO (30022)

Port-au-Prince, , Haiti

IMPACTA Barranco Clinical Research Site (11301)

Lima, , Peru

IMPACTA San Miguel Clinical Research Site (11302)

Lima, , Peru

San Juan City Hospital (5031)

San Juan, , Puerto Rico

University of Puerto Rico Pediatric HIV/AIDS Research Program (6601)

San Juan, , Puerto Rico

Siriraj Hospital Mahidol University CRS (5115)

Bangkok, Ratchathewi,, Thailand

Bhumibol Adulyadej Hospital (5124)

Bangkok, , Thailand

Prapokklao Hospital (5123)

Chanthaburi, , Thailand

Chiang Mai University (31784)

Chiang Mai, , Thailand

Chiang Rai Regional Hospital (5116)

Chiang Rai, , Thailand

Chonburi Hospital (5125)

Chon Buri, , Thailand

Phayao Provincial Hospital (5122)

Phayao, , Thailand

Countries

United States; Argentina; Botswana; Brazil; China; Haiti; Peru; Puerto Rico; Thailand

References

U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 with Clarification dated August 2009, which can be found on the DAIDS RSC Web site: http://rsc.tech-res.com

Reference Type: BACKGROUND

Manual for Expedited Reporting of Adverse Events to DAIDS, Version 2.0, January 2010.

Reference Type: BACKGROUND

Currier JS, Britto P, Hoffman RM, Brummel S, Masheto G, Joao E, Santos B, Aurpibul L, Losso M, Pierre MF, Weinberg A, Gnanashanmugam D, Chakhtoura N, Klingman K, Browning R, Coletti A, Mofenson L, Shapiro D, Pilotto J; 1077HS PROMISE Team. Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 >/= 400 cells/mm3. PLoS One. 2017 May 10;12(5):e0176009. doi: 10.1371/journal.pone.0176009. eCollection 2017.

Reference Type: DERIVED

PMID: 28489856 (View on PubMed)

Related Links

http://www.impaactnetwork.org/studies/1077HS.asp

Related Info

http://apps.who.int/iris/handle/10665/43699

WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-related Disease in Adults and Children (World Health Organization 2007).

Other Identifiers

U01AI068632

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IMPAACT 1077HS

Identifier Type: -

Identifier Source: org_study_id