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

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ClinicalTrials.gov Identifier: NCT00955968
Recruitment Status : Completed
First Posted : August 10, 2009
Results First Posted : February 16, 2018
Last Update Posted : August 7, 2018
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

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.

Condition or disease Intervention/treatment Phase
HIV Infection Drug: Highly active antiretroviral therapy (HAART) Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1653 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: IMPAACT 1077HS: HAART Standard Version of the Promoting Maternal and Infant Survival Everywhere (PROMISE) Study
Actual Study Start Date : January 2010
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Continue HAART
Continue receiving HAART within 0-42 days after delivery or other pregnancy outcome.
Drug: 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.


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





Primary Outcome Measures :
  1. Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    AIDS defining illness, serious non-AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.


Secondary Outcome Measures :
  1. Incidence Rate of AIDS - Defining Illness [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    AIDS defining illness, refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.

  2. Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    Serious non - AIDS defining cardiovascular, renal, or hepatic event, or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.

  3. Incidence Rate of Deaths [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    The incidence rate was obtained by using the Kaplan-Meier method.

  4. Incidence Rate of HIV/AIDS Related Events [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    HIV/AIDS related events refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.

  5. Incidence Rate of HIV/AIDS Related Events or Death [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    HIV/AIDS related events or death refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.

  6. Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    HIV/AIDS related events or WHO Clinical Stage 2 or 3 events refers to illness/diagnoses listed in Appendix II of the protocol. These events were reviewed and confirmed by an Endpoint review group. The incidence rate was obtained by using the Kaplan-Meier method.

  7. Incidence Rate of Grade 2 and Above Toxicity [ Time Frame: All laboratory measures were done at entry,4 and 12 weeks after, and then every 3 months until study end. Signs and Symtoms were recorded from study entry to study end. All were followed until July 7, 2015 (an average of 125 weeks of follow-up) ]
    The toxicity events included all grade 2 and higher hematology or chemistry events and grade 3 or 4 sign or symptoms. 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). The incidence rate was obtained by using the Kaplan-Meier method.

  8. Incidence Rate of Cardiovascular or Other Metabolic Events [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated.

  9. Incidence Rate of Other Targeted Medical Conditions [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated.

  10. Incidence Rate of Any Condition Outlined in Appendix II of Protocol or Death [ Time Frame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. Given the results of the primary analyses it was decided that this outcome was no longer scientifically important. No resources and funding was allocated.

  11. Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm [ Time Frame: At time of confirmation of VF. HIV-1 RNA testing to identify VF was done at week 4, 12, 24, and every 12 weeks thereafter until study end at an average of 125 weeks. If HIV-1 RNA was above 1000 copies/ml, confirmatory testing was done within 4 weeks. ]
    VF was defined as two successive measurements of HIV-1 RNA above 1000 copies/ml at or after 24 weeks of HAART. HIV drug resistance was defined using the Stanford database (Version 6.2)

  12. Medication Adherence [ Time Frame: Measured at baseline, after 4 - 12 and 24 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. The analyses are planned to be completed by May 2018, after which results will be reported to ct.gov.

  13. Quality of Life [ Time Frame: Measured at baseline, after 4 - 12 and 24 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. The analyses are planned to be completed by May 2019, after which results will be reported to ct.gov.

  14. Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers [ Time Frame: Measured at baseline, after 4 and 12 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses conditional on primary results and funding. This outcome required additional funding for laboratory testing which was not available and so this outcome is not reported.

  15. Cost Effectiveness and Feasibility of Treatment Models [ Time Frame: Measured at baseline, after 4 - 12 and 24 weeks, and then every 6 months until study termination. All participants were followed until July 7, 2015 (an average of 125 weeks of follow-up). ]
    This outcome was intended as an exploratory analyses and was not included in the primary analyses. Given the results of the primary analyses and changes in WHO guidelines to recommend lifelong antiretroviral therapy, the protocol team decided that this outcome was no longer scientifically important. No resources and funding was allocated.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00955968


  Hide Study Locations
Locations
United States, California
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
United States, Colorado
University of Colorado (5052)
Aurora, Colorado, United States
United States, District of Columbia
Georgetown University (1008)
Washington, District of Columbia, United States
Howard University (5044)
Washington, District of Columbia, United States
Washington Hospital Center (5023)
Washington, District of Columbia, United States
United States, Florida
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
United States, Illinois
Ann & Robert H Lurie Children's Hospital of Chicago (4001)
Chicago, Illinois, United States
United States, Louisiana
Tulane University (5095)
New Orleans, Louisiana, United States
United States, Maryland
Johns Hopkins University School of Medicine (5092)
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Medical Center (5011)
Boston, Massachusetts, United States
United States, Michigan
Wayne State University/Children's Hospital of Michigan (5041)
Detroit, Michigan, United States
United States, New York
Bronx-Lebanon Hospital Center (5114)
Bronx, New York, United States
Jacobi Medical Center (5013)
Bronx, New York, United States
Metropolitan Hospital (5003)
New York, New York, United States, 10029
SUNY Stony Brook University Medical Center (5040)
Stony Brook, New York, United States
United States, North Carolina
Duke University Medical Center (4701)
Durham, North Carolina, United States
United States, Pennsylvania
Pitt CRS (1001)
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St Jude Children's Research Hospital (6501)
Memphis, Tennessee, United States
United States, Texas
Baylor College of Medicine Texas Children's Hospital (3801)
Houston, Texas, United States
United States, Washington
Seattle Children's Hospital (5017)
Seattle, Washington, United States
Argentina
Hospital General de Agudos (5082)
Buenos Aires, Argentina
Botswana
Gaborone Prevention/Treatment Clinical Research Site (12701)
Gaborone, Botswana
Molepolole Prevention/Treatment Clinical Research Site (12702)
Gaborone, Botswana
Brazil
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)
Sao Paulo, Brazil
China, Guangxi
Guangxi Center for HIV/AIDS Prevention and Control (30274)
Nanning, Guangxi, China
Haiti
Les Centres GHESKIO (30022)
Port-au-Prince, Haiti
Peru
IMPACTA Barranco Clinical Research Site (11301)
Lima, Peru
IMPACTA San Miguel Clinical Research Site (11302)
Lima, Peru
Puerto Rico
San Juan City Hospital (5031)
Rio Piedra, Puerto Rico, 00927
University of Puerto Rico Pediatric HIV/AIDS Research Program (6601)
San Juan, Puerto Rico
Thailand
Siriraj Hospital Mahidol University CRS (5115)
Bangkok, Ratchathewi,, Thailand, 10700
Bhumibol Adulyadej Hospital (5124)
Bangkok, Thailand
Prapokklao Hospital (5123)
Chantaburi, Thailand, 22000
Chiang Mai University (31784)
Chiang Mai, Thailand, 50200
Chiang Rai Regional Hospital (5116)
Chiang Rai, Thailand
Chonburi Hospital (5125)
Chonburi, Thailand, 20000
Phayao Provincial Hospital (5122)
Phayao, Thailand, 56000
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Study Chair: Judith S. Currier, MD, MS University of California, Los Angeles

Additional Information:
Publications:
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
Manual for Expedited Reporting of Adverse Events to DAIDS, Version 2.0, January 2010.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00955968     History of Changes
Other Study ID Numbers: IMPAACT 1077HS
U01AI068632 ( U.S. NIH Grant/Contract )
First Posted: August 10, 2009    Key Record Dates
Results First Posted: February 16, 2018
Last Update Posted: August 7, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:
HIV Infection
HAART
Maternal Health

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases