Telephone Support to Improve Adherence to Anti-HIV Medications

A Randomized Trial of Enhanced Nursing Telephone Support to Improve Medication Self-Management and Viral Outcomes of Antiretroviral Therapy-Experienced Patients

This study tested a system of nursing telephone support to determine if it improves adherence to antiretroviral therapy (ART) in at-risk, treatment-experienced people.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Behavioral: Enhanced nursing telephone support; Behavioral: Standard care

Detailed Description

Antiretroviral therapy (ART) is only successful in treating HIV when people take all the medications prescribed to them when and how they are instructed. However, a third or more of patients on ART are not able to adhere to their medication regimens. Therefore, making sure that these patients stay healthy involves making sure they are motivated and informed about the importance of adhering to their ART. Nurses can deliver interventions to motivate and inform patients through regularly scheduled phone calls. These calls allow nurses to check in between clinic visits, are convenient to patients, and are cost efficient. This study tested an enhanced telephone support intervention provided by nurses that aimed to improve ART adherence and treatment outcomes.

Follow-up for this study lasted 72 weeks. Participants were randomly assigned to receive either care as usual or the enhanced telephone support intervention plus care as usual. The telephone support intervention involved phone calls made weekly for the first 8 weeks of the study and then every 2 weeks for the next 40 weeks. Nurses made these calls at a time and place participants chose. During the calls, nurses provided information, motivational enhancement, and problem-solving skills.

Study assessments took place at study entry and after 12, 24, 48, and 72 weeks. Assessments measured CD4 cell count, HIV viral load, adherence, and illness events. Adherence was measured through questionnaires and an electronic pill cap.

This study was closed early to both accrual and follow-up due to low recruitment. The study aimed to enroll 296 participants. The actual study accrual at the time of early closing was 59 participants.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama Therapeutics CRS
  • California
    • San Diego, California, United States, 92103
      • Ucsd, Avrc Crs
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS (2701)
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center ACTG
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ACTG CRS
    • Boston, Massachusetts, United States, 02118
      • Bmc Actg Crs (104)
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Univ. Hosp. CRS (31476)
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School-Adult Clinical Research Ctr. CRS
  • New York
    • New York, New York, United States, 10011
      • Cornell CRS
    • New York, New York, United States, 10032
      • HIV Prevention & Treatment CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Unc Aids Crs
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Adult CRS
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Therapeutics CRS
  • Texas
    • Dallas, Texas, United States, 75208
      • 31443 Trinity Health and Wellness Center CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Enrollment in an AIDS Clinical Trials Group (ACTG) treatment study that is an approved A5251 parent or coenrolling partner study ("ACTG parent study participant") or not enrolled in one of the ACTG parent studies, but receiving routine HIV patient care at an institution that was also an ACTG-funded site ("ACTG clinic patient participant").
• Virologic failure on combination antiretroviral therapy (ART), with an HIV-1 genotype conducted on or soon after the failure, within 16 weeks prior to entry. Availability of HIV-1 genotype results at entry.
• History of prior nonadherence to ART during the past year documented either by patient self-report or recorded in the patient's medical record
• Most recent HIV-1 RNA value of at least 200 copies/mL, obtained within 90 days prior to study entry and measured using any FDA-approved test for quantifying HIV-1 RNA
• Initiating or restarting an ART regimen with 2 or more active ARV medications within 3 days after randomization. The regimen must have been selected for the participant prior to the time of randomization for A5251. An active ARV medication was defined as a medication to which the participant was expected to be susceptible based on HIV-1 resistance testing, as specified in the ACTG parent study, or determined by the participant's health care provider per standard of care.

Exclusion Criteria:

• No regular access to a phone. Candidates without phones may have elected to participate by calling the HIV nurse specialists using an 800 number, rather than being called by the HIV nurse specialist.
• Coenrollment in another adherence trial, unless approved by the A5251 study chair
• Current incarceration
• Any condition that, in the opinion of the site investigator, would have compromised the candidate's ability to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enhanced nursing telephone support with standard care; Participants received enhanced nursing telephone support plus care as usual.	Behavioral: Enhanced nursing telephone support; Weekly phone calls by study nurses for 8 weeks and then calls every 2 weeks for 40 weeks; nurses could schedule more frequent calls at their discretion. Calls provided information, motivational enhancement, problem-solving skills, and affective support.; Behavioral: Standard care; Usual ACTG site care.
Active Comparator: Standard care; Participants received care as usual.	Behavioral: Standard care; Usual ACTG site care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Virologic Suppression	Number of participants with virologic suppression, defined as HIV-1 RNA at less than 200 copies/mL at week 48.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Premature Antiretroviral Therapy (ART) Regimen Discontinuation	Number of premature ART regimen discontinuations, defined as the first substitution, subtraction, or addition of one or more ARVs made to the initial study regimen.	From study entry to Week 72
Change in CD4 Cell Count at Week 12	Change in CD4 cell count from baseline at week 12, calculated as Week 12 CD4 minus baseline CD4.	Baseline and Week 12
Change in CD4 Cell Count at Week 24	Change in CD4 cell count from baseline at Week 24, calculated as Week 24 CD4 minus baseline CD4.	Baseline and Week 24
Change in CD4 Cell Count at Week 48	Change in CD4 cell count from baseline at Week 48, calculated as Week 48 CD4 minus baseline CD4.	Baseline and Week 48
Confirmed Virologic Failure	Number of participants with confirmed virologic failure. Virologic failure is defined as confirmed HIV-1 RNA ≥200 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 20 weeks after the date of randomization).	Week 24 through Week 72
Cost of the Adherence Telephone Interventions	This outcome was planned to be analyzed if the intervention was found to be successful. However, the intervention was not determined to be successful.	Week 48
Number of Participants With Illness Events or Mortality	Number of participants who had acute illnesses and mortality during follow-up. The categories of illness events and mortality are not mutually exclusive.	Measured from entry to Week 72 or premature study discontinuation
Number of Participants With Virological Suppression	Number of participants with virological suppression, defined as HIV-1 RNA less than 200 copies/mL.	Measured from entry to Week 72 or premature study discontinuation
Number of Participants Who Received Last Telephone Call if Prior to the End of Defined Intervention Period	Number of participants whose last telephone call received occurred prior to the end of the defined intervention period.	Measured from entry to Week 72 or premature study discontinuation
Intervention Dosage Score for Enhanced Nursing Telephone Support (Total Percentage of Scheduled Calls Successfully Delivered)	Intervention dosage score for enhanced nursing telephone support. This is the total percentage of scheduled calls successfully delivered.	Measured at Week 12
Intervention Dosage Score for Enhanced Nursing Telephone Support (Total Amount of Time Spent in Calls)	Intervention dosage score for enhanced nursing telephone support. This is the total amount of time spent in calls overall.	Week 12
Number of Participants With Virologic Suppression, Defined as HIV-1 RNA Less Than 200 Copies/mL at Week 12	Number of participants with virologic suppression, defined as HIV-1 RNA less than 200 copies/mL, at week 12.	Week 12
Number of Participants With Virologic Suppression, Defined as HIV-1 RNA Less Than 200 Copies/mL at Week 24.	Number of participants with virologic suppression, defined as HIV-1 RNA less than 200 copies/mL, at week 24.	Week 24
Number of Participants With Virologic Suppression, Defined as HIV-1 RNA Less Than 1,000 Copies/mL at Week 12	Number of participants with virologic suppression, defined as HIV-1 RNA less than 1,000 copies/mL, at week 12.	Week 12
Number of Participants With Virologic Suppression, Defined as HIV-1 RNA Less Than 1,000 Copies/mL at Week 24	Number of participants with virologic suppression, defined as HIV-1 RNA less than 1,000 copies/mL, at week 24.	Week 24
Number of Participants With Virologic Suppression, Defined as HIV-1 RNA Less Than 1,000 Copies/mL at Week 48	Number of participants with virologic suppression, defined as HIV-1 RNA less than 1,000 copies/mL, at week 48.	Measured at Week 48
Antiretroviral (ARV) Medication Adherence at Week 12 Using ACTG Adherence Questionnaire	ARV medication adherence at week 12, as measured by the ACTG adherence questionnaire index. This questionnaire index is on a 0-100 scale, with higher scores indicating higher adherence.	Week 12
Antiretroviral (ARV) Medication Adherence at Week 24 Using ACTG Adherence Questionnaire	ARV medication adherence at week 24, as measured by the ACTG adherence questionnaire index. The ACTG adherence questionnaire index is on a 0-100 scale where higher scores indicate better adherence.	Week 24
Antiretroviral (ARV) Medication Adherence at Week 12 Using Four Day Recall	ARV medication adherence at week 12, as measured by four day recall, i.e. "Missed doses in last 4 days".	Week 12
Antiretroviral (ARV) Medication Adherence at Week 24 Using Four Day Recall	ARV medication adherence, as measured by four day recall, i.e. "Missed doses in last 4 days".	Week 24
Antiretroviral (ARV) Medication Adherence at Week 12 Using Visual Analog Scale	ARV medication adherence at week 12, as measured by the visual analog scale. The visual analog scale is a 0-100% scale that measures the percentage of HIV medication taken in the past month.	Week 12
Antiretroviral (ARV) Medication Adherence at Week 24 Using Visual Analog Scale	ARV medication adherence at Week 24, as measured by the visual analog scale. The visual analog scale is a 0-100% scale that measures the percentage of HIV medication taken in the past month.	Week 24
Quality of Life Measured by Euro-QoL - Mobility	Quality of life measured by Euro-QoL - Question 1: Mobility.	Week 24
Quality of Life Measured by Euro-QoL - Self-Care	Quality of Life Measured by Euro-QoL - Question 2: Self-Care.	Week 24
Quality of Life Measured by Euro-QoL - Usual Activities	Quality of Life Measured by Euro-QoL - Question 3: Usual activities.	Week 24
Quality of Life Measured by Euro-QoL - Pain/Discomfort	Quality of Life Measured by Euro-QoL - Question 4: Pain/Discomfort.	Week 24
Quality of Life Measured by Euro-QoL - Anxiety/Depression	Quality of Life Measured by Euro-QoL - Question 5: Anxiety/Depression.	Week 24

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Nancy R. Reynolds, PhD, RN, NP, Yale University School of Nursing

Publications and helpful links

General Publications

• Reynolds NR, Testa MA, Su M, Chesney MA, Neidig JL, Frank I, Smith S, Ickovics J, Robbins GK; AIDS Clinical Trials Group 731 and 384 Teams. Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial. J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):62-8. doi: 10.1097/QAI.0b013e3181582d54.
• Sitta R, Lert F, Gueguen A, Spire B, Dray-Spira R; VESPA group. No variability across centers in adherence and response to HAART in French hospitals: results from the ANRS-EN12-VESPA study. J Acquir Immune Defic Syndr. 2009 Dec;52(5):643-7. doi: 10.1097/QAI.0b013e3181b26eb9.
• Zaric GS, Bayoumi AM, Brandeau ML, Owens DK. The cost-effectiveness of counseling strategies to improve adherence to highly active antiretroviral therapy among men who have sex with men. Med Decis Making. 2008 May-Jun;28(3):359-76. doi: 10.1177/0272989X07312714. Epub 2008 Mar 18.
• Robbins GK, Cohn SE, Harrison LJ, Smeaton L, Moran L, Rusin D, Dehlinger M, Flynn T, Lammert S, Wu AW, Safren SA, Reynolds NR. Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251. HIV Clin Trials. 2016 Jul;17(4):165-72. doi: 10.1080/15284336.2016.1189754.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: October 1, 2009
• First Submitted That Met QC Criteria: October 1, 2009
• First Posted (Estimate): October 2, 2009

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Treatment; Adherence; treatment experienced; Telephone Intervention; Adherence Intervention
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ACTG A5251; 1U01AI068636 (U.S. NIH Grant/Contract); 10632