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Report for Clinical Trial NCT01352715

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT01352715 HIV-1 Infection

10 Interventions

Name: Lopinavir/ritonavir

Description: 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.
Type: Drug
Group Labels: 2

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

Name: Lopinavir/ritonavir

Description: Lopinavir 400mg/ritonavir 100mg (given as three LPV 133.3 mg/RTV 33.3 mg fixed-dose combination soft gelatin capsules) orally twice daily, with food, throughout follow-up.
Type: Drug
Group Labels: 2

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

Name: Raltegravir

Description: Raltegravir 400 mg tablet orally twice daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm A: LPV/r plus RAL

Name: Emtricitabine/tenofovir disoproxil fumarate

Description: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300mg fixed-dose combination tablet orally once daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs

Name: Abacavir/lamivudine/zidovudine

Description: Abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet orally twice daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs

Name: Abacavir/lamivudine

Description: Abacavir 600 mg/lamivudine 300 mg fixed-dose combination tablet orally once daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs

Name: Lamivudine/zidovudine

Description: Lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet orally twice daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs

Name: Abacavir

Description: 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.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs

Name: Zidovudine

Description: Zidovudine 300 mg tablet orally twice daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs

Name: Lamivudine

Description: Lamivudine 150 mg tablet orally twice daily, with or without food, throughout follow-up.
Type: Drug
Group Labels: 1

Arm B: LPV/r plus best available NRTIs


Primary Outcomes

Description: 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.

Measure: Cumulative Probability of Virologic Failure by Week 48

Time: From study entry to week 48

Secondary Outcomes

Description: Change in CD4+ cell count was calculated as CD4+ cell count at week 48 minus CD4+ cell count at study entry.

Measure: Change in CD4+ Cell Count From Baseline to Week 48

Time: Study entry and week 48

Description: Mutations were defined as major IAS mutations in the IAS-USA July 2014 list. New mutations were those detected at virologic failure but not at baseline.

Measure: 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

Time: From study entry through to week 96

Description: The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

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

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

Description: Discontinuation of randomized treatment for toxicity included participant decision to discontinue for low grade toxicity. Within class NRTI changes were not considered discontinuations.

Measure: Number of Participants Discontinuing Randomized Treatment for Toxicity

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

Description: AIDS-defining events were those recognized by the Centers for Disease Control (CDC) and World Health Organization (WHO)

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

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

Description: Serious non-AIDS diagnoses were based on ACTG Appendix 60 Diagnosis Codes

Measure: Number of Participants With a Targeted Serious Non-AIDS-defining Event or Death

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

Description: The percentage of total study time that participants were in hospital.

Measure: Percentage of Time Spent in Hospital

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

Description: Fasting was for 8 hours and the metabolic panel was drawn locally.

Measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides, and Glucose From Baseline

Time: Study entry and week 48

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 3 SNPs

SNPs


1 K65R

The most significant of these mutations include M184V, thymidine analogue mutations (TAMs), Q151M complex, and K65R. --- M184V --- --- Q151M --- --- K65R ---

The presence of K65R would result in resistance to most NRTIs (leaving only zidovudine (ZDV) and possibly abacavir (ABC) as active second-line options); the presence of multiple TAMs and/or Q151M alone or in complex with other mutations would also result in resistance to most NRTIs. --- K65R ---


2 M184V

The most significant of these mutations include M184V, thymidine analogue mutations (TAMs), Q151M complex, and K65R. --- M184V ---

Recent data suggest that patients with isolated M184V-related NRTI resistance who subsequently switch to a boosted PI plus lamivudine (3TC)- or emtricitabine (FTC)-based regimen may achieve HIV-1 RNA suppression without the need to switch to more complex regimens [1]. --- M184V ---

Detection of an isolated M184V NRTI mutation is possible when resources allow for early diagnosis of virologic failure. --- M184V ---


3 Q151M

The most significant of these mutations include M184V, thymidine analogue mutations (TAMs), Q151M complex, and K65R. --- M184V --- --- Q151M ---

The presence of K65R would result in resistance to most NRTIs (leaving only zidovudine (ZDV) and possibly abacavir (ABC) as active second-line options); the presence of multiple TAMs and/or Q151M alone or in complex with other mutations would also result in resistance to most NRTIs. --- K65R --- --- Q151M ---



HPO Nodes