SNPMiner Trials (Home Page)
Report for Mutation N88S
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 5 clinical trials
Clinical Trials
1 Phase IIIb Multicenter, Single Arm, Open-Label Pilot Study to Evaluate the Effectiveness and Safety of Maintenance With Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in HIV-Infected Patients Evidencing Virologic Suppression OREY (Only REYataz) Study
The main purpose is to explore whether atazanavir/ritonavir (ATV/RTV) single enhanced protease inhibitor therapy can maintain virologic suppression without a marked increase in virologic failure.
NCT00337467 Human Immunodeficiency Virus (HIV) Infections Drug: Atazanavir + Ritonavir MeSH:Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes
HPO:Immunodeficiency
International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. --- V32I --- --- L33F --- --- M46I --- --- I47V --- --- G48V --- --- I50L --- --- I54M --- --- I76V --- --- I82A --- --- I84V --- --- N88S ---
Primary Outcomes
Description: Treatment Failure through Week 48 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 48 or study discontinuation before Week 48. Virological rebound is defined as confirmed on-treatment HIV ribonucleic acid (RNA) >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy.
Measure: Percentage of Participants With Treatment Failure Through Week 48 Time: Week 48Secondary Outcomes
Description: Treatment Failure through Week 96 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 96 or study discontinuation before Week 96. In addition, treatment failure defined based on HIV RNA >= 50 c/mL, latter analysis performed on treated subjects with baseline HIV RNA < 50 c/mL.
Measure: Percentage of Participants With Treatment Failure Through Week 96 Time: Week 96Description: Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.
Measure: Percentage of Participants With Virological Rebound Through Week 48 Time: Week 48Description: Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.
Measure: Percentage of Participants With Virological Rebound Through Week 96 Time: Week 96Description: This Kaplan-Meier life table reports the cumulative proportion of participants without treatment failure up to the end of the respective time interval. Failure time is measured from the start of study therapy, and is based on the earliest event defining failure (virologic rebound at or before Week 96, or discontinuation prior to Week 96).
Measure: Cumulative Proportion of Participants Without Treatment Failure Through Week 100 Time: Through Week 100Description: Virologic rebound is defined as confirmed on-study HIV RNA ≥ 400 c/mL or last on-study HIV RNA ≥ 400 c/mL followed by treatment discontinuation.
Measure: Proportion of Participants With Virologic Rebound Through Week 96 Time: Through Week 96Measure: Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 Time: Baseline, Week 24
Measure: Mean Change From Baseline in CD4 Cell Count at Week 48 Time: Baseline, Week 48
Measure: Mean Change From Baseline in CD4 Cell Count at Week 96 Time: Baseline, Week 96
Description: AE=any new untoward medical occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship to treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. AE grades are: mild (1), moderate (2), severe (3), life-threatening (4), and death (5).
Measure: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs Time: From Baseline through Week 96Description: Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Measure: Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 48 Time: Baseline, Week 48Description: Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Measure: Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 96 Time: Baseline, Week 96Description: International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.
Measure: Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48 Time: Week 48Description: International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.
Measure: Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96 Time: Week 962 Prospective Clinical Trial to Assess Safety and Efficacy of DRV/r(TMC 114/r), ETV(TMC 125) and MK-0518 in Addition to OBT in HIV-1 Infected Patients With Limited to No Treatment Options ANRS 139 TRIO
The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: darunavir, etravirine and MK-0518 (raltegravir) in patients who have multi-resistant viruses and limited treatment options. An optimized background regimen that may include nucleoside reverse transcriptase inhibitors (NRTIs) and enfuvirtide can be added, if possible, to this combination. Patients will undergo treatment for 48 weeks and virological efficacy will be evaluated at week 24.
NCT00460382 HIV Infections Drug: raltegravir potassium Drug: darunavir/ritonavir Drug: etravirine Drug: Optimized background regimen MeSH:HIV Infections
- Genotypic resistance testing at the screening visit: - Protease inhibitor mutations: over or equal to 3 primary protease inhibitor mutations among: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54M, L76V, V82A/F/L/T/S, I84V, N88S and L90M (IAS list 2006) but below or equal to 3 mutations among the following: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V et L89V (virus sensitivity to darunavir/ritonavir). - Reverse transcriptase mutations: over or equal to 3 NRTI mutations (among IAS list) and below or equal to 3 mutations among: A98G, L100I, K101Q/P/E, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V/C/H/L, Y188C/H/L, G190A/C/E/Q/S, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F (virus sensitivity to etravirine) Exclusion Criteria: - Non effective barrier contraception in women of child bearing potential - Pregnant women or women who are breastfeeding - Opportunistic infection at the acute phase - Decompensated cirrhosis (stage B or C of Child-Pugh score) - Malignancy requiring chemotherapy or radiotherapy - Contraindicated medications being taken by the patient (listed in protocol) - Allergy to the active substances and expedients of darunavir, etravirine and raltegravir. --- D30N --- --- V32I --- --- L33F --- --- M46I --- --- I47A --- --- G48V --- --- I50L --- --- I54M --- --- L76V --- --- V82A --- --- I84V --- --- N88S ---
Primary Outcomes
Measure: Proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at week 24 Time: week 24Secondary Outcomes
Measure: Proportions of patients with HIV RNA levels of less than 50 copies/ml at week 48, with HIV RNA levels of less than 400 copies/ml at weeks 24 and 48 Time: week 24 and 48Measure: HIV RNA level evolution between baseline and week 48 Time: from week 0 to 48
Measure: HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48 Time: from week 0 to 48
Measure: Number and type of resistance mutations in case of virologic failure occurrence Time: from week 0 to 48
Measure: CD4 lymphocyte count and proportion evolution between baseline and week 48 Time: from week 0 to 48
Measure: HIV infection progression Time: from week 0 to 48
Measure: Frequency of the study regimen modifications and interruption Time: from week 0 to 48
Measure: Study regimen tolerance Time: from week 0 to 48
Measure: Study regimen adherence Time: from week 0 to 48
Measure: Association between study drugs' minimum concentrations at week 4 and week 12 and virologic success at week 24 Time: from week 4 to 24
Measure: Evolution of pharmacokinetics parameters of study drugs in the PK substudy Time: betwwen week 1 and 4
3 Phase 2 Dose-escalating, P-C, D-B, Parallel Group Study in HIV Treatment-experienced Patients to Evaluate the Safety, Tolerability and Efficacy of PA103001-04 Administered as Functional Monotherapy for 14 Days *(PART B)
The purpose of this study is to evaluate antiretroviral activity of up to five different oral doses administered for two weeks of bevirimat versus placebo in HIV treatment experienced patients, who have documented genotypic resistance to at least one major mutation from the IAS-USA list (2007)of resistance mutations for NRTIs, NNRTIs, or PIs. Patients will also be monitored for side effects, and the pharmacokinetics of bevirimat will be determined.
NCT00511368 HIV Infections Drug: matching placebo Drug: Bevirimat MeSH:HIV Infections
- Have documented evidence of genotypic resistance in their medical records (at screening) or have resistance at screening by genotype to any major mutation from the IAS-USA list of resistance drug mutations, defined as: NRTI resistance: M41L, K65R, D67N, K70R, K70E, L74V, Y115F, M184V, M184V/I, L210W, T215Y/F, K219Q/E; NNRTI resistance: L100I, K103N, V106M, V106A/M, V108I, Y181C, Y181C/I, Y188L, Y188C/L/H, G190S/A, G190A, P225H; Major PI resistance: D30N, V32I, L33F, M46I/L, I47V/A, G48V, I50L, I50V, I54M/L, L76V, V82A/F/T, V82A/F/T/S, V82L/T, I84V, N88S, L90M - Be receiving an antiretroviral therapy regimen containing at least 3 drugs (regimens containing ritonavir must not exceed a total daily dose of 400 mg) which has been unchanged for at least 8 weeks prior to initial screening. --- M41L --- --- K65R --- --- D67N --- --- K70R --- --- K70E --- --- L74V --- --- Y115F --- --- M184V --- --- M184V --- --- L210W --- --- T215Y --- --- K219Q --- --- L100I --- --- K103N --- --- V106M --- --- V106A --- --- V108I --- --- Y181C --- --- Y181C --- --- Y188L --- --- Y188C --- --- G190S --- --- G190A --- --- P225H --- --- D30N --- --- V32I --- --- L33F --- --- M46I --- --- I47V --- --- G48V --- --- I50L --- --- I50V --- --- I54M --- --- L76V --- --- V82A --- --- V82A --- --- V82L --- --- I84V --- --- N88S ---
Primary Outcomes
Measure: HIV-1 RNA change from baseline over the first 14 days of study Time: 14 daysSecondary Outcomes
Measure: safety and tolerability; pharmacokinetics Time: 14 days4 A Phase II, Randomized Trial of Open-Label Truvada With Darunavir/Ritonavir Versus Multiclass Therapy With Truvada, Darunavir/Ritonavir, Maraviroc and Raltegravir in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects
The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses: - Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication. - Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa. - Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.
NCT00525733 HIV Infections Drug: darunavir 800 mg Drug: FTC 200 mg/TDF 300mg Drug: Maraviroc Drug: Raltegravir Drug: Ritonavir 100 mg MeSH:Infection HIV Infections
Major resistance-associated mutations include: NRTI: K65R or inserts Q151M, M184V/I, PI: I50L/V, I84V, N88S. --- K65R --- --- Q151M --- --- M184V --- --- I50L --- --- I84V --- --- N88S ---
Primary Outcomes
Measure: The Primary Outcome of This Study is the Proportion of Patients Having Detectable HIV-1 RNA Using the Single Copy Assay After 48 Weeks of Treatment and the Study Hypothesis is That New Treatment is Better Than the Control Group. Time: 48 weeks5 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 ---
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