Study of Options for Second-Line Effective Combination Therapy (SELECT)

NCT01352715 | Completed Phase 3 Results DMC

• 3 other identifiers: ACTG A52731U01AI0686365UM1AI068634
• Study Type: interventional
• Target: 515
• Locations: 9 countries
• Sites: 16

Brief Summary

The study was conducted on people who were taking their first anti-HIV drug regimen (including an Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), a type of anti-HIV drug) but the drugs in this regimen were not doing a good job of fighting their HIV infection. The main purpose of this study was to compare two other anti-HIV drug regimens to see how well they fight HIV. The study also looked at how well participants tolerate the drug regimens and how safe they are. The study was designed to determine whether taking the combination of lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) works as well as what is usually used for second-line therapy: LPV/r plus the best-available nucleoside (nucleotide) reverse transcriptase inhibitor (NRTI) combination. Testing a regimen that does not include any NRTIs was important because NRTIs may no longer work for patients who received them as part of their first treatment regimen.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Cumulative Probability of Virologic Failure by Week 48

  The primary endpoint was time to virologic failure. Virologic failure was defined as confirmed viral load \>400 copies/mL at or after week 24. The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 48 was used.

  From study entry to week 48

Secondary Outcomes (8)

• Change in CD4+ Cell Count From Baseline to Week 48

  Study entry and week 48

• Number of Participants With HIV-1 Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase in Participants With Virologic Failure at Baseline and at Time of Virologic Failure

  From study entry through to week 96

• Number of Participants With Grade 3 or Higher Adverse Event (AE) at Least One Grade Higher Than Baseline

  From start of randomized treatment to off randomized treatment (up to 96 weeks)

• Number of Participants Discontinuing Randomized Treatment for Toxicity

  From Start of Randomized Treatment to Off Randomized Treatment (up to 96 weeks)

• Number of Participants With a New AIDS-defining Events or Death

  From study entry throughout follow-up (up to 96 weeks)

Study Arms (2)

Arm A: LPV/r plus RAL

EXPERIMENTAL

Participants were administered LPV/r plus RAL orally twice daily throughout follow-up.

Drug: Lopinavir/ritonavir; Drug: Raltegravir

Arm B: LPV/r plus best available NRTIs

EXPERIMENTAL

Participants were administered LPV/r orally twice daily, plus NRTI options provided by the study, to include the best available NRTIs (listed below) throughout follow-up- * FTC/TDF orally twice daily * ABC/3TC/ZDV orally twice daily * ABC/3TC orally once daily * 3TC/ZDV orally twice daily * ABC 300mg orally twice daily or 600 mg once daily * 3TC orally twice daily * ZDV orally twice daily

Drug: Lopinavir/ritonavir; Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Abacavir/lamivudine/zidovudine; Drug: Abacavir/lamivudine; Drug: Lamivudine/zidovudine; Drug: Abacavir; Drug: Zidovudine; Drug: Lamivudine

Interventions

Lopinavir/ritonavir DRUG

Lopinavir 400mg/ritonavir 100mg (given as two LPV 200mg/RTV 50mg fixed-dose combination tablets) orally twice daily, with or without food, throughout follow-up.

Also known as: Aluvia, LPV/r, Kaletra

Arm A: LPV/r plus RAL; Arm B: LPV/r plus best available NRTIs

Raltegravir DRUG

Raltegravir 400 mg tablet orally twice daily, with or without food, throughout follow-up.

Also known as: Isentress, RAL

Arm A: LPV/r plus RAL

Emtricitabine/tenofovir disoproxil fumarate DRUG

Emtricitabine 200 mg/tenofovir disoproxil fumarate 300mg fixed-dose combination tablet orally once daily, with or without food, throughout follow-up.

Also known as: Truvada, FTC/TDF

Arm B: LPV/r plus best available NRTIs

Abacavir/lamivudine/zidovudine DRUG

Abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet orally twice daily, with or without food, throughout follow-up.

Also known as: Trizivir, ABC/3TC/ZDV

Arm B: LPV/r plus best available NRTIs

Abacavir/lamivudine DRUG

Abacavir 600 mg/lamivudine 300 mg fixed-dose combination tablet orally once daily, with or without food, throughout follow-up.

Also known as: Epzicom, ABC/3TC

Arm B: LPV/r plus best available NRTIs

Lamivudine/zidovudine DRUG

Lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet orally twice daily, with or without food, throughout follow-up.

Also known as: Combivir, CBV, 3TC/ZDV

Arm B: LPV/r plus best available NRTIs

Abacavir DRUG

Abacavir 300 mg tablet orally twice daily or 600 mg (given as two 300 mg tablets) once daily, with or without food, throughout follow-up.

Also known as: Ziagen, ABC

Arm B: LPV/r plus best available NRTIs

Zidovudine DRUG

Zidovudine 300 mg tablet orally twice daily, with or without food, throughout follow-up.

Also known as: Retrovir, ZDV

Arm B: LPV/r plus best available NRTIs

Lamivudine DRUG

Lamivudine 150 mg tablet orally twice daily, with or without food, throughout follow-up.

Also known as: Epivir, 3TC

Arm B: LPV/r plus best available NRTIs

Eligibility Criteria

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

You may qualify if:

• HIV-1 infected
• Confirmation of first-line virologic failure
• Certain laboratory values obtained within 45 days prior to study entry. More information on this criterion can be found in the study protocol.
• Negative pregnancy test within 48 hours prior to study entry.
• Must refrain from participating in a conception process, and, if participating in sexual activity that could lead to pregnancy, must use at least one acceptable type of contraceptive. More information on this criterion can be found in the study protocol.
• Karnofsky performance score \>= 70 within 45 days prior to study entry.
• Ability and willingness of participant or legal guardian/representative to provide informed consent.
• No intention to relocate away from current geographical area of residence for the duration of study participation.

You may not qualify if:

• Use of any immunomodulator, HIV vaccine, or other investigational therapy within 45 days prior to study entry, with the exception of a tapering course of corticosteroids as acute therapy for pneumocystis jiroveci pneumonia (PCP) or acute asthma/chronic obstructive pulmonary disease flare and/or prednisone at a daily dose of \<10 mg (physiologic replacement dose).
• If the potential participant has had resistance testing, evidence of broad NRTI cross-resistance that, in the opinion of the investigator, would not allow selection of an effective NRTI combination if the participant were randomized to the LPV/r + best available NRTIs arm.
• Prior exposure to a Protease Inhibitor.
• Known history of congenital long QT syndrome, hypokalemia, or planned use of other drugs that prolong the QT interval.
• Pregnancy or breast-feeding.
• Known history of chronic hepatitis B virus (HBV) infection or current HBV infection defined by the presence of hepatitis B surface antigen in serum or plasma.
• Active tuberculosis (TB) requiring treatment with rifampicin.
• Previously diagnosed malignancies other than basal cell carcinoma and cutaneous Kaposi sarcoma.
• Requirement for taking any medications that are prohibited with the study drugs. More information on this criterion can be found in the study protocol, section 5.4.
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
• Active drug or alcohol use or dependence or other condition that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

Sponsors & Collaborators

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

Study Sites (16)

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, 21045, Brazil

Location

BJ Medical College CRS (31441)

Pune, Maharashtra, 411001, India

Location

NARI Pune CRS

Pune, Maharashtra, India

Location

Y.R.G Ctr, for AIDS Research and Education (11701)

Chennai, India

Location

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)

Eldoret, 30100, Kenya

Location

College of Med. JHU CRS (30301)

Blantyre, Malawi

Location

University of North Carolina Lilongwe CRS (12001)

Lilongwe, Malawi

Location

San Miguel CRS

San Miguel, Lima region, Peru

Location

Barranco CRS (11301)

Lima, 18 PE, Peru

Location

Wits HIV CRS (11101)

Johannesburg, Gauteng, South Africa

Location

Durban Adult HIV CRS (11201)

Durban, 4013 SF, South Africa

Location

Soweto ACTG CRS (12301)

Johannesburg, South Africa

Location

Univ. of Witwatersrand CRS (11101)

Johannesburg, South Africa

Location

Kilimanjaro Christian Medical CRS

Kilimanjaro Region, Moshi, Tanzania

Location

Chiang Mai University ACTG CRS (11501)

Chiang Mai, 50202, Thailand

Location

UZ-Parirenyatwa CRS (30313)

Harare, Zimbabwe

Location

Related Publications (3)

• [1] Hull M, Moore D, Harris M, et al. A lamivudine (3TC)-based backbone in conjunction with a boosted protease inhibitor (PI) is sufficient to achieve virologic suppression in the presence of M184V mutations. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12-15, 2009; San Francisco, California. Abstract H-916.

  BACKGROUND

• Torres TS, Harrison LJ, La Rosa AM, Zheng L, Cardoso SW, Ulaya G, Akoojee N, Kadam D, Collier AC, Hughes MD; for AIDS Clinical Trials Group (ACTG) A5273 Study Group. Poor quality of life and incomplete self-reported adherence predict second-line ART virological failure in resource-limited settings. AIDS Care. 2021 Oct;33(10):1340-1349. doi: 10.1080/09540121.2021.1874275. Epub 2021 Jan 23.

  PMID: 33487029 DERIVED

• La Rosa AM, Harrison LJ, Taiwo B, Wallis CL, Zheng L, Kim P, Kumarasamy N, Hosseinipour MC, Jarocki B, Mellors JW, Collier AC; ACTG A5273 Study Group. Raltegravir in second-line antiretroviral therapy in resource-limited settings (SELECT): a randomised, phase 3, non-inferiority study. Lancet HIV. 2016 Jun;3(6):e247-58. doi: 10.1016/S2352-3018(16)30011-X. Epub 2016 Apr 18.

  PMID: 27240787 DERIVED

MeSH Terms

Interventions

Lopinavir; lopinavir-ritonavir drug combination; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; abacavir, lamivudine, and zidovudine drug combination; abacavir, lamivudine drug combination; lamivudine, zidovudine drug combination; abacavir; Zidovudine; Lamivudine

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrrolidinones; Pyrrolidines; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; 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; Zalcitabine

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

• Alberto M La Rosa, MD

  Asociacion Civil Impacta Salud y Educacion - Miraflores, CRS

  STUDY CHAIR

• Ann C Collier, MD

  Univ. of Washington Clinical HIV Research Program (CHIRP)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: May 12, 2011
• Study Start: March 13, 2012
• Primary Completion: October 29, 2014
• Study Completion: October 29, 2014
• Last Updated: August 5, 2021
• Results First Posted: January 6, 2016

Record last verified: 2021-08

Locations

PE (2); ZA (4); IN (3); MA (2); TH (1); BR (1); TA (1); KE (1); ZI (1)