Clinical trial NCT00955968: IMPAACT 1077HS: Examining Benefits of HAART Continuation in Postpartum Women
Official title: IMPAACT 1077HS: HAART Standard Version of the Promoting Maternal and Infant Survival Everywhere (PROMISE) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: HIV Infection
HAART
Maternal Health
Lead sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2009-08-10
Enrollment: 1653
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Incidence Rates of AIDS - Defining Illness, Serious Non-AIDS Defining, Cardiovascular, Renal, Hepatic Event, or Death
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
Secondary outcomes:
measure: Incidence Rate of AIDS - Defining Illness
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rates of Serious Non- AIDS Defining Cardiovascular, Renal or Hepatic Event
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of Deaths
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of HIV/AIDS Related Events
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of HIV/AIDS Related Events or Death
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of HIV/AIDS Related Events or WHO Clinical Stage 2 or 3 Events
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of Grade 2 and Above Toxicity
timeFrame: All laboratory measures were done at entry,4 and 12 weeks after, and then every 3 months until study end. Signs and Symptoms were recorded from study entry to study end. All were followed until July 7, 2015 (an average of 125 weeks of follow-up)
measure: Incidence Rate of Cardiovascular or Other Metabolic Events
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of Other Targeted Medical Conditions
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Incidence Rate of Any Condition Outlined in Appendix II of Protocol or Death
timeFrame: From study entry to study termination, all participants were followed until July 7, 2015 (an average of 125 weeks of follow-up).
measure: Number of Virologic Failure (VF) Participants With HIV Resistance in the Continue HAART Arm
timeFrame: 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.
measure: Medication Adherence - Last Time Missed Medications
timeFrame: week 0, 48 and 96
measure: Medication Adherence - How Closely Followed Schedule
timeFrame: week 0, 48 and 96
measure: Medication Adherence - How Often Follow Instructions
timeFrame: week 0, 48 and 96
measure: Medication Adherence - Missed Dose Within Past 4 Days
timeFrame: week 0, 48 and 96
measure: Quality of Life - General Health Outcome
timeFrame: week 0, 48 and 96
measure: Quality of Life (QoL) - Health Rating Score
timeFrame: week 0, 48 and 96
measure: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers
timeFrame: 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).
measure: Cost Effectiveness and Feasibility of Treatment Models
timeFrame: 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).
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: University of Southern California MCA Center (5048)
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA (5112)
state: California
city: San Diego
country: United States
facility: UCSD Mother-Child-Adolescent HIV Program (4601)
state: California
city: Torrance
country: United States
facility: Harbor (UCLA) Medical Center (5045)
state: California
city: Aurora
country: United States
facility: University of Colorado (5052)
state: Colorado
city: Washington
country: United States
facility: Howard University (5044)
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University (1008)
state: District of Columbia
city: Washington
country: United States
facility: Washington Hospital Center (5023)
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic and Treatment Center (5055)
state: Florida
city: Jacksonville
country: United States
facility: University of Florida at Jacksonville (5051)
state: Florida
city: Miami
country: United States
facility: University of Miami Pediatric/Perinatal Clinical Research Site (4201)
state: Florida
city: Tampa
country: United States
facility: University of South Florida at Tampa (5018)
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago (4001)
state: Illinois
city: New Orleans
country: United States
facility: Tulane University (5095)
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine (5092)
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center (5011)
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Children's Hospital of Michigan (5041)
state: Michigan
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital Center (5114)
state: New York
city: Bronx
country: United States
facility: Jacobi Medical Center (5013)
state: New York
city: New York
country: United States
facility: Metropolitan Hospital (5003)
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook University Medical Center (5040)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (4701)
state: North Carolina
city: Pittsburgh
country: United States
facility: Pitt CRS (1001)
state: Pennsylvania
city: Memphis
country: United States
facility: St Jude Children's Research Hospital (6501)
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine Texas Children's Hospital (3801)
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital (5017)
state: Washington
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos (5082)
city: Gaborone
country: Botswana
facility: Gaborone Prevention/Treatment Clinical Research Site (12701)
city: Gaborone
country: Botswana
facility: Molepolole Prevention/Treatment Clinical Research Site (12702)
city: Belo Horizonte
country: Brazil
facility: School of Medicine, University of Minas Gerais - FUNDEP (5073)
city: Caxias do Sul
country: Brazil
facility: University Caxias do Sul (5084)
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao (5117)
city: Porto Alegre
country: Brazil
facility: Hospital Santa Casa (5098)
city: Rio de Janeiro
country: Brazil
facility: Hospital dos Servidores do Estado (5072)
city: Rio de Janeiro
country: Brazil
facility: Hospital Geral De Nova Igaucu (5097)
city: Rio de Janeiro
country: Brazil
facility: Instituto de Puericultura E Pediatria Martagao Geseira - FUJB (5071)
city: Sao Paulo
country: Brazil
facility: Ribeirao Preto Medical School, University of Sao Paulo (5074)
city: Nanning
country: China
facility: Guangxi Center for HIV/AIDS Prevention and Control (30274)
state: Guangxi
city: Port-au-Prince
country: Haiti
facility: Les Centres GHESKIO (30022)
city: Lima
country: Peru
facility: IMPACTA Barranco Clinical Research Site (11301)
city: Lima
country: Peru
facility: IMPACTA San Miguel Clinical Research Site (11302)
city: San Juan
country: Puerto Rico
facility: San Juan City Hospital (5031)
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Pediatric HIV/AIDS Research Program (6601)
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University CRS (5115)
state: Ratchathewi,
city: Bangkok
country: Thailand
facility: Bhumibol Adulyadej Hospital (5124)
city: Chanthaburi
country: Thailand
facility: Prapokklao Hospital (5123)
city: Chiang Mai
country: Thailand
facility: Chiang Mai University (31784)
city: Chiang Rai
country: Thailand
facility: Chiang Rai Regional Hospital (5116)
city: Chon Buri
country: Thailand
facility: Chonburi Hospital (5125)
city: Phayao
country: Thailand
facility: Phayao Provincial Hospital (5122)
Study officials:
affiliation: University of California, Los Angeles
name: Judith S. Currier, MD, MS
role: STUDY_CHAIR
References:
citation: 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
citation: Manual for Expedited Reporting of Adverse Events to DAIDS, Version 2.0, January 2010.
citation: 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.