SNPMiner Trials (Home Page)
Report for Mutation I54V
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 4 clinical trials
Clinical Trials
1 A Phase IIIB, Randomized Trial of Open-Label Efavirenz or Atazanavir With Ritonavir in Combination With Double-Blind Comparison of Emtricitabine/Tenofovir or Abacavir/Lamivudine in Antiretroviral-Naive Subjects
Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.
NCT00118898 HIV Infections Drug: Abacavir/Lamivudine Drug: Atazanavir Drug: Efavirenz Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Ritonavir Drug: Abacavir/Lamivudine placebo Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo MeSH:HIV Infections
Major mutations were defined by International AIDS Society-United States of America (2008), as well as T69D, L74I, G190C/E/Q/T/V for reverse transcriptase and L24I, F53L, I54V/A/T/S, G73C/S/T/A, N88D for protease.. Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.. AIDS-defining illnesses were defined per CDC category C definition. --- T69D --- --- L74I --- --- G190C --- --- L24I --- --- F53L --- --- I54V ---
Primary Outcomes
Description: Blood samples for determining virologic failure were obtained at visit weeks 16 and 24 , and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks after randomization and before 24 weeks, or >=200 copies/mL at or after 24 weeks. The 5th percentile for time to virologic failure is the time (in weeks) at which 5% of the participants have experienced virologic failure.
Measure: Time From Randomization to Virologic Failure Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
Measure: Time From Treatment Dispensation to a Grade 3/4 Safety Event Time: All follow-up while on initially assigned regimen; the median (25th, 75th percentile) follow-up while on initial regimen was 120 (54, 156) weeks and the range was 0 to 205 weeks.Description: Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Time From Treatment Dispensation to Treatment Modification Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsSecondary Outcomes
Description: Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsMeasure: The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL Time: At Weeks 48 and 96
Measure: Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL Time: At Weeks 48 and 96
Description: Change was calculated as the CD4 count at Week 48 (or at Week 96) minus the baseline CD4 count (mean of pre-entry and entry values).
Measure: Change in CD4 Count (Cells/mm3) From Baseline Time: At Weeks 48 and 96Description: Emergence of resistant virus was assessed by genotypic testing performed at Stanford University for all participants who met criteria for virologic failure and retrospectively on baseline samples from these participants. Major mutations were defined by International AIDS Society-United States of America (2008), as well as T69D, L74I, G190C/E/Q/T/V for reverse transcriptase and L24I, F53L, I54V/A/T/S, G73C/S/T/A, N88D for protease.
Measure: Number of Participants With Virologic Failure and Emergence of Major Resistance Time: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: AIDS-defining illnesses were defined per CDC category C definition. HIV-1 related events were defined per CDC category B definition. Events underwent study chair review for classification. See link below for more details. http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
Measure: Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting Total Cholesterol Level From Baseline Time: At Weeks 48 and 96Description: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline Time: At Weeks 48 and 96Description: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline Time: At Weeks 48 and 96Description: Only fasting results are included. The protocol did not require that samples be collected fasting.
Measure: Change in Fasting Triglyceride Level From Baseline Time: At Weeks 48 and 96Other Outcomes
Description: Participants were to be followed for 96 weeks after the last enrollment. Accrual was expected to take 96 weeks, thus the planned follow-up time was 96 to 192 weeks, dependent on when in the study the participant enrolled. This outcome summarizes that total amount of actual follow-up in weeks from randomization to last contact.
Measure: Amount of Study Follow-up Time: Follow-up time was variable, median follow-up was 138 weeksDescription: Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks.
Measure: Number of Participants With Virologic Failure Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks.
Measure: Cumulative Probability of Not Experiencing Virologic Failure Time: At week 48 and 96Description: Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables. As-treated analysis censored at 1st modification of initially assigned regimen, participants who never started treatment were excluded.
Measure: Number of Participants With a Grade 3/4 Safety Event Time: Over all study follow-up while on initially assigned treatment, median follow-up was 120 weeksDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables. As-treated analysis censored at 1st modification of initially assigned regimen, participants who never started treatment were excluded.
Measure: Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event Time: At week 48 and 96Description: Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Number of Participants With Treatment Modification Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Cumulative Probability of Not Experiencing Treatment Modification Time: At week 48 and 96Description: Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Number of Participants With Regimen Failure Time: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for detailsDescription: Kaplan-Meier estimate of the cumulative survival probability at week 48 and 96. Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
Measure: Cumulative Probability of Not Experiencing Regimen Failure Time: At week 48 and 962 Open-Label, Single-Centre, Randomised Pilot Study to Evaluate Immunovirological and Clinical Evolution of a Combination With Nucleoside Analogues/Nucleotides (Trizivir +Tenofovir) in Multiresistant Patients With Virological Failure
To evaluate whether the combined therapy of two nucleosides plus one nucleotide (Trizivir + TDF) manages to keep CD4 lymphocytes stable in patients with HIV infection on antiretroviral treatment that present virological failure and multiple resistance to antiretrovirals.
NCT00356616 HIV Infections Drug: Trizivir (AZT+3HT+Abacavir) twice daily Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily MeSH:HIV Infections
- 5 or more mutations that confer resistance to PI of the following: I10F/I/R/V, V32I, M46I/L, I54V/M/L, V82A/F/T/S/V, I84V/A/C, L90M. --- I10F --- --- V32I --- --- M46I --- --- I54V ---
Primary Outcomes
Measure: Variations in the immune status of patients in each group throughout follow-up. Time: 48 weeksSecondary Outcomes
Measure: Percentage of patients that increase viral load by > 0.5 log Time: weeks 12, 24, 36 and 48Measure: Percentage of patients that increase viral load by > 100,000 copies/mL Time: weeks 12, 24, 36 and 48
Measure: Percentage of patients that present some clinical event, B or C classification according to the CDC. Time: during the 48 weeks of follow-up
Measure: Percentage of patients that present clinical or analytical adverse effects degree > 2 according to the WHO classification. Time: weeks 12, 24, 36 and 48
Measure: Percentage of patients that drop out of treatment. Time: weeks 12, 24, 36 and 48
Measure: Percentage of patients that drop out of the study due to intolerance or adverse effects. Time: weeks 12, 24, 36 and 48
Measure: Percentage of change in lipid determinations. Time: weeks 12, 24, 36 and 48 with regard to baseline
Measure: Percentage of patients that report changes, improvement or worsening in redistribution of body fat. Time: weeks 12, 24, 36 and 48
Measure: Percentage of patients that present adherence to the antiretroviral treatment > 95%. Time: weeks 12, 24, 36 and 48
Measure: Percentage of patients that present improvement in the quality of life (MOS-HIV) and satisfaction questionnaires. Time: weeks 12, 24, 36 and 48
Measure: Percentage of patients that present an increase in the number of active drugs. Time: at the end of the study
3 Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r) in Adolescents With CD4 + T Cells > 350 Cells/mm3 Initiating HAART
This study proposes to evaluate a pre-DHHS guideline of HAART initiation and then de-intensification management strategy in adolescents with mild immunosuppression and compare changes in CD4% from baseline to week 48 and then during de-intensification.
NCT00491556 HIV Infections Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy Procedure: Standard Care MeSH:HIV Infections
The following genotypic mutations exclude subjects from participation in ATN 061: Major ATV mutations I50L; I84V; N88D/S, Major PI mutations including: D30N; V32I; L33I/F/V; M46I/L; I47V/A; G48V; I50V/L; I54V/L/A/M/T/S; L76V; V82A/F/T/S/L; L90M, Any major PI mutation as defined by the most current IAS-USA Drug Resistance Mutations Figures that would adversely affect a subject's future PI choices, Major RT mutations: Q151M and 69 insertion complex; Decisions regarding the selection of an NRTI backbone for subjects with NRTI resistance mutations other than those described above will be made by the site PI in consultation with the protocol chair or his designee. --- I50L --- --- I84V --- --- N88D --- --- D30N --- --- V32I --- --- L33I --- --- M46I --- --- I47V --- --- G48V --- --- I50V --- --- I54V ---
Primary Outcomes
Measure: Difference in CD4+ T Cell Percentage Between Week 0 and Week 48 Time: Week 0 and Week 48Measure: Difference in CD4+ T Cell Percentage Between Week 48 and Week 152 Time: 152 Weeks
Secondary Outcomes
Measure: Difference in CD4+ T Cell Count Between Week 0 and Week 48 Time: 48 weeksMeasure: Difference in CD4+ T Cell Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD4+ Naïve T Cell Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD4+ Naïve T Cell Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD4+ Termed Central Memory (TCM) Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD4+ TCM Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD4+ Effector Memory (TEM)Ro Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD4+ TEMRo Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD4+ TEMRa Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD4+ TEMRa Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8+ Naïve T-Cell Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8+ Naïve T-Cell Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8+ TCM Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8+ TCM Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8+ TEMRo Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8+ TEMRo Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8+ TEMRa Count Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8+ TEMRa Count Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 Naïve CD28 Cell Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 Naïve CD28 Cell Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 Naïve CD38 Cell Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 Naïve CD38 Cell Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 Naïve CD57 Cell Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 Naïve CD57 Cell Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 Naïve T-Cell Percentage Expressing Human Leukocyte Antigen-D Related (HLA-DR) Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 Naïve T-Cell Percentage Expressing HLA-DR Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TCM CD28 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TCM CD28 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TCM CD38 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TCM CD38 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TCM CD57 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TCM CD57 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TCM HLA-DR Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TCM HLA-DR Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRo CD28 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRo CD28 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRo CD38 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRo CD38 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRo CD57 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRo CD57 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRO HLADR Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRo HLA-DR Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRa CD28 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRa CD28 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRa CD38 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRa CD38 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRa CD57 Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRa CD57 Percentage Between Week 48 and Week 152 Time: 152 weeks
Measure: Difference in CD8 TEMRa HLA-DR Percentage Between Week 0 and Week 48 Time: 48 weeks
Measure: Difference in CD8 TEMRa HLA-DR Percentage Between Week 48 and Week 152 Time: 152 weeks
4 An Open-Label Phase 3B Study in HIV-Infected Individuals With Viremia on or After Their First-Line Non-Nucleoside Reverse Transcriptase Inhibitor or Integrase Inhibitor-Based Regimen and Starting a Second-Line Regimen Consisting of ATV/RTV or DRV/RTV With an Optimized NRTI Backbone
The purpose of this study is to determine the proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 in patients who failed their first line therapy containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an integrase inhibitor
NCT01605084 HIV Drug: Atazanavir Drug: Darunavir Drug: Ritonavir Drug: Optimized NRTI backbone
An NRTI or PI (reported with or without ritonavir) with a "partially sensitive" net assessment will not be considered "fully sensitive" 4. Mentally able to participate in the study 5. Men and women ≥ 18 years old - Women of child bearing potential who engage in vaginal intercourse and who are not clinically sterilized must use highly effective methods of birth control during the study Exclusion Criteria: 1. Screening HIV genotype showing presence at baseline of any of the following Protease inhibitor (PI) Mutation Patterns associated with genotypic resistance to Atazanavir sulfate/ Ritonavir or Darunavir/Ritonavir will lead to exclusion: 1. Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V) 2. Subjects with a major mutation to Atazanavir sulfate consisting of N88S 3. Subjects with more than 3 of any of the following Atazanavir sulfate related mutations:D30N, M36I/V, M46I/L/T, I54V/L/T/M/A, A71V/T/I/G, G73S/A/C/T, V77I, V82A/F/T/S/I, I84V/A, N88D or L90M 2. Subjects with < 1 fully active NRTI on PhenoSense report, other than lamivudine and emtricitabine 3. Diagnosed with active tuberculosis 4. Chronic hepatitis B infection 5. Hepatitis C-positive patients who are not clinically stable or need treatment during the study period 6. --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- N88S --- --- M36I --- --- M46I --- --- I54V ---
Primary Outcomes
Measure: Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL Time: At Week 48Secondary Outcomes
Measure: Proportion of subjects with HIV-1 RNA < 50 c/mL Time: At week 24Measure: Change from baseline in CD4 cell count Time: Baseline (Week 0) and at week 48
Measure: Incidence rates of serious adverse event (SAEs) and adverse events (AEs) leading to discontinuation Time: up to week 48
Measure: Incidence rates of antiretroviral resistance measured by newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failure Time: up to week 48
Measure: Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence Time: Week 48