Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected Adults

NCT00608569 | Completed Results

• 2 other identifiers: ACTG A52341U01AI068636
• Study Type: interventional
• Target: 529
• Locations: 7 countries
• Sites: 8

Brief Summary

Highly active antiretroviral therapy (HAART) has led to better health and survival rates among people with HIV/AIDS. The purpose of this study was to measure the effect of trained partner supervision when taking medication versus self-administered therapy in HIV infected participants. These participants have had their first virologic failure on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen and were starting a protease inhibitor (PI)-based HAART regimen at study entry.

Conditions

HIV Infections

Keywords

Drug Therapy, Combination; HIV Non-Nucleoside Reverse Transcriptase Inhibitors; HIV Protease Inhibitors; Viral Load; Virologic Failure

Outcome Measures

Primary Outcomes (1)

• Confirmed Virologic Failure at or Prior to Week 48

  Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) \<1 log10 copies/mL below the baseline level and \>400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) \>400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤50 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 48 was reported.

  At or prior to Week 48

Secondary Outcomes (7)

• Confirmed Virologic Failure at or Prior to Week 24

  At or prior to Week 24

• CD4 Count at Follow-up Visits

  At Weeks 4, 12, 24, 36, and 48

• CD8 Count at Follow-up Visits

  At week 4, 12, 24, 36, and 48

• Time to First Grade 3 or 4 Lab Event

  52 weeks since randomization

• Time to First Grade 3 or 4 Sign or Symptom

  52 weeks since randomization

Study Arms (2)

mDOT arm

EXPERIMENTAL

Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.

Drug: Lopinavir/ritonavir; Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Tenofovir disoproxil fumarate; Drug: Zidovudine; Drug: Emtricitabine

non-mDOT arm

ACTIVE COMPARATOR

Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.

Drug: Lopinavir/ritonavir; Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Tenofovir disoproxil fumarate; Drug: Zidovudine; Drug: Emtricitabine

Interventions

Lopinavir/ritonavir DRUG

Two tablets (200-mg lopinavir and 50 mg ritonavir in each tablet), taken orally twice daily

Also known as: LPV/RTV, LPV/r, Kaletra

mDOT arm; non-mDOT arm

Emtricitabine/Tenofovir disoproxil fumarate DRUG

200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily

Also known as: FTC/TDF, Truvada

mDOT arm; non-mDOT arm

Tenofovir disoproxil fumarate DRUG

300-mg tablet taken orally once daily

Also known as: TDF, Viread

mDOT arm; non-mDOT arm

Zidovudine DRUG

300-mg tablet taken orally twice daily

Also known as: ZDV, Retrovir

mDOT arm; non-mDOT arm

Emtricitabine DRUG

200-mg tablet taken orally once daily

Also known as: FTC, Emtriva

mDOT arm; non-mDOT arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infected
• Have experienced or currently experiencing first baseline virologic failure on first NNRTI-based HAART regimen with no history of virologic failure on another regimen OR discontinued first NNRTI-based HAART regimen without the recommendations of clinicians and currently experiencing virologic failure with no history of virologic failure on another regimen. More information on this criterion can be found in the protocol.
• Confirmed virologic failure within 45 days of study entry
• Receiving one of the following NNRTI-based regimens for at least 16 weeks prior to study entry: ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP or d4T+3TC+EFV
• Able to identify a close friend, relative, or spouse who is willing to serve as a partner
• Intend to stay in current geographical area of residence for the duration of the study
• Agree to use LPV/rtv with MEMS caps and take the tablets out of the container only at dosing
• Willing to use acceptable forms of contraception
• Ability and willingness of participant or legal guardian/representative to give written informed consent.
• Required laboratory values obtained within 45 days prior to study entry.
• Negative serum or urine pregnancy test obtained within 48 hours prior to study entry for women of reproductive potential.
• Not a participant
• Friend, family member, or spouse who knows of the participant's HIV status. Partners do not have to live with participants.
• Willing to attend a 1- to 2-hour taped training session prior to study entry
• Willing to attend study visits with participant at study screening; entry; and Weeks 4, 8, 12, 24, and 52

You may not qualify if:

• Use of any immunomodulator, HIV vaccine, or other investigational therapy within 45 days of study entry
• Prior treatment with any PI
• Previously diagnosed cancer other than basal cell carcinoma and cutaneous Kaposi's sarcoma
• Use of rifampin or rifabutin within 45 days of study entry or plan use of rifampin or rifabutin
• Requirement for taking any medications that are prohibited by this study. More information on this criterion can be found in the protocol.
• Known allergy to the study medications or their formulations
• Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study
• Acute illness requiring hospitalization within 14 days of study entry
• Active tuberculosis (TB) infection
• Currently incarcerated
• Participation as a partner in this study
• Participation with no access to telephones
• Abnormal laboratory values
• Pregnant, breastfeeding, or intend to become pregnant
• A participant in this study

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (9)

Gaborone Prevention/Treatment Trials CRS

Gaborone, Botswana

Location

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, 21045, Brazil

Location

Les Centres GHESKIO CRS

Bicentenaire, Port-au-Prince, HT-6110, Haiti

Location

San Miguel CRS

San Miguel, Lima region, Peru

Location

Barranco CRS

Lima, 18, Peru

Location

Wits HIV CRS

Johannesburg, Gauteng, South Africa

Location

JCRC CRS

Kampala, Uganda

Location

Kalingalinga Clinic CRS

Lusaka, Zambia

Location

UZ-Parirenyatwa CRS

Harare, Zimbabwe

Location

Related Publications (7)

• Bangsberg DR, Kroetz DL, Deeks SG. Adherence-resistance relationships to combination HIV antiretroviral therapy. Curr HIV/AIDS Rep. 2007 May;4(2):65-72. doi: 10.1007/s11904-007-0010-0.

  PMID: 17547827 BACKGROUND

• Conway B. The role of adherence to antiretroviral therapy in the management of HIV infection. J Acquir Immune Defic Syndr. 2007 Jun 1;45 Suppl 1:S14-8. doi: 10.1097/QAI.0b013e3180600766.

  PMID: 17525686 BACKGROUND

• Goggin K, Liston RJ, Mitty JA. Modified directly observed therapy for antiretroviral therapy: a primer from the field. Public Health Rep. 2007 Jul-Aug;122(4):472-81. doi: 10.1177/003335490712200408.

  PMID: 17639650 BACKGROUND

• Pearson CR, Micek MA, Simoni JM, Hoff PD, Matediana E, Martin DP, Gloyd SS. Randomized control trial of peer-delivered, modified directly observed therapy for HAART in Mozambique. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):238-44. doi: 10.1097/QAI.0b013e318153f7ba.

  PMID: 17693890 BACKGROUND

• Mantshonyane L, Roy J, Levy MZ, Wallis CL, Bar K, Godfrey C, Collier A, LaRosa A, Zheng L, Sun X, Gross R. Participants Switching to Second-Line Antiretroviral Therapy with Susceptible Virus Display Inferior Adherence and Worse Outcomes: An Observational Analysis. AIDS Patient Care STDS. 2021 Dec;35(12):467-473. doi: 10.1089/apc.2021.0115. Epub 2021 Nov 16.

  PMID: 34788110 DERIVED

• De Boni RB, Zheng L, Rosenkranz SL, Sun X, Lavenberg J, Cardoso SW, Grinsztejn B, La Rosa A, Pierre S, Severe P, Cohn SE, Collier AC, Gross R. Binge drinking is associated with differences in weekday and weekend adherence in HIV-infected individuals. Drug Alcohol Depend. 2016 Feb 1;159:174-80. doi: 10.1016/j.drugalcdep.2015.12.013. Epub 2015 Dec 24.

  PMID: 26774947 DERIVED

• Gross R, Zheng L, La Rosa A, Sun X, Rosenkranz SL, Cardoso SW, Ssali F, Camp R, Godfrey C, Cohn SE, Robbins GK, Chisada A, Wallis CL, Reynolds NR, Lu D, Safren SA, Hosey L, Severe P, Collier AC; ACTG 5234 team. Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234): a multinational randomised trial. Lancet HIV. 2015 Jan;2(1):e12-9. doi: 10.1016/S2352-3018(14)00007-1. Epub 2014 Dec 11.

  PMID: 26424232 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Lopinavir; lopinavir-ritonavir drug combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Zidovudine; Emtricitabine

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)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Thymidine; Dideoxynucleosides

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Robert Gross, MD, MSCE

  University of Pennsylvania

  STUDY CHAIR

• Alberto La Rosa, MD

  Asociación Civil Impacta Salud y Educación, Peru

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2008
• First Posted: February 6, 2008
• Study Start: March 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 12, 2018
• Results First Posted: November 15, 2013

Record last verified: 2018-09

Locations

BO (1); PE (2); UG (1); BR (1); ZA (1); ZI (1); HA (1)