SNPMiner Trials (Home Page)
Report for Mutation G73S
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 6 clinical trials
Clinical Trials
1 A Randomized, Open-Label Study Assessing Safety, Tolerability and Efficacy of an Induction-Maintenance Treatment Strategy Including Lopinavir/Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine Versus Efavirenz Plus Tenofovir Disoproxil Fumarate and Emtricitabine in Antiviral-naïve HIV-1/HCV Co-Infected Subjects
The purpose of this study is to determine whether a simplified lopinavir/ritonavir-based therapy will continue to keep the viral load at very low levels after initial treatment with a combination of Kaletra (lopinavir/ritonavir) plus tenofovir and emtricitabine.
NCT00121017 HIV Infection Hepatitis C Drug: Kaletra (lopinavir/ritonavir) Drug: Sustiva (efavirenz) Drug: Truvada (emtricitabine/tenofovir disoproxil fumarate) MeSH:Hepatitis C
- The screening HIV-1 genotype resistance report suggests resistance or possible resistance to the study RTI(s) or lopinavir/ritonavir; Evidence of possible resistance to efavirenz; Presence of one of the following mutations: RT L1001, K103N, V106A or M, V108I, Y181C or I, Y188L, G190A or S, P225H, M230L; Evidence of possible resistance to emtricitabine or lamivudine; Presence of one of the following mutations: RTm184V or I; Evidence of possible resistance to tenofovir; Presence of RT K65R or insertion at codon 69, or Presence of 2 or more of the following mutations: RTm41L, D67N, K70R, L210W; any change at T215, K219Q or evidence of possible resistance to lopinavir/ritonavir; Presence of one or more of the following mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, 190M or Presence of 3 or more of the following mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L; any change at I54, A71V or T, G73S. --- K103N --- --- V106A --- --- V108I --- --- Y181C --- --- Y188L --- --- G190A --- --- P225H --- --- M230L --- --- K65R --- --- D67N --- --- K70R --- --- L210W --- --- K219Q --- --- I47V --- --- G48V --- --- I50V --- --- V82A --- --- I84V --- --- L10F --- --- K20M --- --- L24I --- --- V32I --- --- L33F --- --- M36I --- --- M46I --- --- F53L --- --- A71V --- --- G73S ---
Primary Outcomes
Measure: The proportion of subjects with a plasma HIV-1 RNA level below 50 copies/mL at Week 96.Secondary Outcomes
Measure: Vital signsMeasure: Physical examinations
Measure: Clinical laboratory tests
2 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 --- --- L90M --- --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- G73S ---
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 Open Label Phase 3b, 48 wk Pilot Study of the Antiviral Efficacy and Tolerability of Combination of PREZISTA/r and TMC125 When Substituted for Enfuvirtide, Current Protease Inhibitor(s) and NNRTI(s) in Antiretroviral Resistant Patients With Viral Suppression But Who Are Intolerant of Enfuvirtide.
The purpose of this study is to examine the safety, tolerability, and effectiveness of darunavir/ritonavir combined with TMC125 when current protease inhibitor(s), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI(s)) and enfuvirtide are replaced by darunavir/ritonavir and TMC125 in HIV positive patients who can no longer tolerate enfuvirtide and are experiencing viral suppression. Other antiviral drugs in the regimen are to remain unchanged.
NCT00460746 HIV Drug: TMC125, Darunavir; Ritonavir
Exclusion Criteria: - No use of any drug contraindicated in the current US package insert for PREZISTA (darunavir) or in the investigators brochure for TMC125 - No prior or current therapy with PREZISTA (darunavir) or TMC125 - No prior genotypic results demonstrating 3 or more darunavir resistance-associated mutations associated with diminished response to darunavir (V11I, V32I, L33F, I47V, I50V, I54L, I54M, G73S, L76V, I84V or L89V). --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- G73S ---
Primary Outcomes
Measure: Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure. Time: 48 weeksSecondary Outcomes
Measure: Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure. Time: 48 weeksMeasure: CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks. Time: Week 48
Measure: CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks. Time: Week 48
Measure: Median Change From Baseline in Triglycerides at Week 48. Time: Week 48
Measure: Median Change From Baseline in Total Cholesterol at Week 48. Time: Week 48
Measure: Median Change From Baseline in LDL Cholesterol at Week 48. Time: Week 48
Measure: Median Change From Baseline in HDL Cholesterol. Time: Week 48
Measure: Median Change From Baseline in Total Cholesterol (TC) / High Denisty Lipoprotein (HDL) Ratio at Week 48. Time: Week 48
Measure: Median Change From Baseline in Glucose at Week 48. Time: Week 48
4 A Randomized, Open-label Study of Lopinavir/Ritonavir 400/100 mg Tablet Twice Daily + Co-formulated Emtricitabine/Tenofovir Disoproxil Fumarate 200/300 mg Once Daily Versus Lopinavir/Ritonavir 400/100 mg Tablet Twice Daily + Raltegravir 400 mg Twice Daily in Antiretroviral Naive, HIV-1 Infected Subjects
The purpose of this study is to compare the safety, tolerability, and antiviral activity of the lopinavir/ritonavir tablet when administered in combination with reverse transcriptase inhibitors to lopinavir/ritonavir tablets when administered in combination with a human immunodeficiency virus type 1 ( HIV-1) integrase inhibitor in antiretroviral naive HIV-1 infected subjects.
NCT00711009 Human Immunodeficiency Virus Infection Drug: lopinavir/ritonavir (LPV/r) Drug: emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) Drug: raltegravir (RAL) MeSH:Acquired Immunodeficiency Syndrom Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Virus Diseases
HPO:Immunodeficiency
Evidence of lopinavir resistance was more conservatively defined as the presence of 1 or more of these mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, L90M; or presence of at least 3 or more of these mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L, any change to I54, A71V or T, and G73S.. Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey. --- I47V --- --- G48V --- --- I50V --- --- V82A --- --- I84V --- --- L90M --- --- L10F --- --- K20M --- --- L24I --- --- V32I --- --- L33F --- --- M36I --- --- M46I --- --- F53L --- --- A71V --- --- G73S ---
Primary Outcomes
Description: A participant was classified as a responder at the first of 2 consecutive visits with plasma HIV-1 RNA levels below 40 copies/mL. The participant continued to be a responder until one of the following: the participant had 2 consecutive values greater than or equal to 40 copies/mL; the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL; the participant discontinued participation in the study or died.
Measure: Percentage of Participants Responding (Plasma HIV-1 Ribonucleic Acid [RNA] Levels Less Than 40 Copies/Milliliter [mL]) at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm Time: Baseline to Week 48Description: Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Treatment-emergent, moderate or severe drug-related adverse events that occurred in at least 2% of participants in either treatment arm are presented.
Measure: Percentage of Participants With Moderate or Severe Treatment-emergent, Drug-related Adverse Events Time: Week 96Description: Potentially clinically significant laboratory values that occurred in at least 2% of participants in either treatment arm are presented.
Measure: Primary Outcome: Percentage of Participants With Potentially Clinically Significant Laboratory Values Time: Baseline to Week 96Secondary Outcomes
Description: A participant was classified as a responder at the first of 2 consecutive visits with plasma HIV-1 RNA levels below 40 copies/mL. The participant continued to be a responder until one of the following: 1) the participant had 2 consecutive values greater than or equal to 40 copies/mL; the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL; the participant discontinued participation in the study or died.
Measure: Percentage of Participants Responding (Plasma HIV-1 RNA Levels Below 40 Copies/Milliliter [mL]) at Each Visit Based on the FDA Time to Loss of Virologic Response (TLOVR) Algorithm Time: Baseline to Week 96Measure: Mean Change in CD4+ T-Cell Counts From Baseline to Each Visit Time: Baseline to Week 96
Description: Time of loss of virologic response was defined as the first of the following: first of 2 consecutive visits with plasma HIV-1 RNA greater than or equal to 40 copies/milliliter (mL), if the participant previously demonstrated 2 consecutive plasma HIV-1 RNA levels below 40 copies/mL; Study Day 1, if the subject never achieved 2 consecutive plasma HIV-1 RNA levels below 40 copies/mL; the day of the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL.
Measure: Time to Loss of Virologic Response - Percentage of Participants Still Categorized as Responders at Day 672 Time: Baseline to Week 96Description: Resistance to study drugs was defined as described by the International AIDS Society-USA (IAS-USA) Panel. All participants had an HIV-1 drug resistance genotype (lopinavir/ritonavir, tenofovir, or emtricitabine) obtained at the Screening Visit. Beginning at Week 8, if participant's plasma HIV-1 RNA was greater than or equal to 40 copies/milliliter (mL) and was below 40 copies/mL at the previous visit, additional procedures were undertaken to determine if resistance to study drug occurred.
Measure: Number of Participants Who Developed Resistance to Each Drug in the Study Regimen, as Defined by the International AIDS Society-USA (IAS-USA) Panel. Time: Baseline to Week 96Description: Beginning at Week 8, if participant's plasma HIV-1 RNA was greater than/equal to 40 copies/milliliter (mL) and was below 40 copies/mL at the previous visit, additional procedures were undertaken to determine if resistance occurred. Evidence of lopinavir resistance was more conservatively defined as the presence of 1 or more of these mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, L90M; or presence of at least 3 or more of these mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L, any change to I54, A71V or T, and G73S.
Measure: Number of Participants Who Developed Resistance, Defined Conservatively, to Lopinavir Time: Baseline to Week 96Description: The Survey is a brief, comprehensive health status measure used in studies of people with HIV/AIDS. Participants rate their health and mental/emotional condition, how much their health limits physical activities (eating, dressing, bathing, climbing stairs, walking one block, etc.) and social activities (for example, visiting with friends or relatives), and other questions that measure quality of life. The physical component summarizes answers to questions about physical status. Possible scores range from 0 to 100. A higher score indicates better health, and increases indicate improvement.
Measure: Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey Time: Baseline to Week 96Description: The Survey is a brief, comprehensive health status measure used in studies of people with HIV/AIDS. Participants rate their health and mental/emotional condition, how much their health limits physical activities (eating, dressing, bathing, climbing stairs, walking one block, etc.) and social activities (visiting with friends or relatives, etc.), and other questions that measure quality of life. The mental component summarizes answers to questions about emotional and mental wellbeing. Possible scores range from 0 to 100. Higher scores indicates better health, and increases indicate improvement.
Measure: Change From Baseline on Mental Component of Medical Outcomes Study HIV Health Survey Time: Baseline to Week 96Description: The Effectiveness Scale of the TSQM evaluates the participant's satisfaction or dissatisfaction (1=extremely dissatisfied to 7=extremely satisfied) with the ability of the medication to prevent or treat the condition, the way the medication relieves symptoms, the amount of time it takes for the medication to start working, and other questions. Scores are converted to a range of 0 to 100. A higher score indicates greater satisfaction.
Measure: Score on Effectiveness Scale of Treatment Satisfaction Questionnaire for Medication (TSQM) Time: Week 96Description: The Side Effects scale of the TSQM asks if the participant experiences side effects (yes/no), and if so, how bothersome the side effects are, to what extent they interfere with physical health and ability to function (for example, strength and energy levels), to what extent they interfere with mental function (for example, ability to think clearly, stay awake, etc.), and to what extent the side effects affect the participants overall satisfaction with the medication. Scores are converted to a range of 0 to 100. Higher scores indicate less interference and/or less dissatisfaction.
Measure: Score on Side Effects Scale of Treatment Satisfaction Questionnaire for Medication Time: Week 96Description: The Global Satisfaction scale of the TSQM evaluates the participants rating of whether the good things about the medication outweigh the bad things (1=not at all certain to 5=extremely certain) and how satisfied or dissatisfied the participant is with the medication (1=extremely dissatisfied to 7=extremely satisfied). Scores are converted to a range of 0 to 100. Higher scores indicate greater satisfaction.
Measure: Score on Global Satisfaction Scale of Treatment Satisfaction Questionnaire for Medication Time: Week 96Measure: Mean Change From Baseline in Hemoglobin (Grams/Liter) Time: Baseline to Week 96
Description: Hematocrit fraction is the percentage (%) by volume of packed red blood cells (RBCs) in the participant's blood. It was measured using standard clinical laboratory analysis of participants' blood samples.
Measure: Mean Change From Baseline in Hematocrit (Fraction) Time: Baseline to Week 96Measure: Mean Change From Baseline in Red Blood Cell Count (x 10^12/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Platelet Count (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in White Blood Cell Count (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Neutrophils (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Lymphocytes (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Monocytes (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Eosinophils (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Basophils (x 10^9/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Alanine Aminotransferase (Units/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Aspartate Aminotransferase (Units/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Alkaline Phosphatase (Units/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Creatine Phosphokinase (Units/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Total Bilirubin (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Creatinine (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Blood Urea Nitrogen (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Uric Acid (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Inorganic Phosphate (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Calcium (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Sodium (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Potassium (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Chloride (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Bicarbonate (Micromoles/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Albumin (Grams/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Total Protein (Grams/Liter) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Cholesterol (Micromoles/Liter) Time: Baseline to Week 96
Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in High Density Lipoprotein Cholesterol (HDL) (Micromoles/Liter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Low Density Lipoprotein (LDL) (Micromoles/Liter) Time: Baseline to Week 96Measure: Mean Change From Baseline in Low Density Lipoprotein (LDL): High Density Lipoprotein (HDL) Ratio (Ratio) Time: Baseline to Week 96
Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Triglycerides (Micromoles/Liter) Time: Baseline to Week 96Measure: Mean Change From Baseline in Calculated Creatinine Clearance (Milliliters/Second) Time: Baseline to Week 96
Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Fasting Glucose (Millimoles/Liter) Time: Baseline to Week 96Measure: Mean Change From Baseline in Lactate Dehydrogenase (Units/Liter) Time: Baseline to Week 96
Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Lipase (Units/Liter) Time: Baseline to Week 96Measure: Mean Change From Baseline in Magnesium (Millimoles/Liter) Time: Baseline to Week 96
Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Adiponectin (Micrograms/Milliliter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Interleukin-6 (Nanograms/Liter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Lactate (Millimoles/Liter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-1 (Picograms/Milliliter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-2 (Picograms/Milliliter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Leptin (Nanograms/Milliliter) Time: Baseline to Week 96Description: Included in measures of metabolic toxicity
Measure: Mean Change From Baseline in Insulin (Picomoles/Liter) Time: Baseline to Week 96Description: Urine specific gravity is a laboratory test that measures the concentration of all chemical particles in the urine. The measurement produces a ratio of the urine density to water density.
Measure: Mean Change From Baseline in Urine Specific Gravity Time: Baseline to Week 96Measure: Mean Change From Baseline in Urine pH Time: Baseline to Week 96
Measure: Mean Change From Baseline in Sitting Systolic Blood Pressure (mm Hg) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Sitting Diastolic Blood Pressure (mm Hg) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Sitting Heart Rate (Beats Per Minute) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Weight (kg) Time: Baseline to Week 96
Measure: Mean Change From Baseline in Temperature (°F) Time: Baseline to Week 96
Description: Chest circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Participant's chest circumference was measured at 5 cm above the xiphoid process using non-stretchable measuring tape with half centimeter marks.
Measure: Mean Change From Baseline in Chest Measurement (cm) Time: Baseline to Week 96Description: Waist circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Circumference of participant's waist was measured at the level of the navel using non-stretchable measuring tape with half centimeter marks.
Measure: Mean Change From Baseline in Waist Measurement (cm) Time: Baseline to Week 96Description: Arm circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Particpant's arm circumference was measured halfway between the acromial process on the shoulder and the tip of the elbow (olecranon process) using non-stretchable measuring tape with half centimeter marks.
Measure: Mean Change From Baseline in Mid-Arm Measurement (cm) Time: Baseline to Week 96Description: Hip circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Participant was measured at widest width of the hip using non-stretchable measuring tape with half centimeter marks.
Measure: Mean Change From Baseline in Hips Measurement (cm) Time: Baseline to Week 96Description: Mid-thigh circumference is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen. Particpant's thigh circumference was measured halfway between the inguinal crease and the midpoint of the upper border of the patella using non-stretchable measuring tape with half centimeter marks.
Measure: Mean Change From Baseline in Mid-Thigh Measurement (cm) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Fat (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Lean Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Total Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Fat (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in DEXA Scan of Lower Extremity Lean Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Total Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Fat (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Lean Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Fat (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Lean Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan is included in the measures of somatic toxicity, which is characterized by loss of fat in the face, arms, and legs, and increase in fat in the base of the back of the neck and in the abdomen.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Mass (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan of bone mineral content was used to evaluate potential bone effects of treatment.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Content (Grams) Time: Baseline to Week 96Description: The dual energy X-ray absorptiometry (DEXA) scan of bone mineral content was used to evaluate potential bone effects of treatment.
Measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Density (Grams/cm^2) Time: Baseline to Week 965 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 --- --- A71V --- --- G73S ---
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
6 An Open Label Randomized Clinical Trial, to Evaluate the Treatment With Darunavir/Ritonavir + Lamivudine Once Daily Versus Continuing With Darunavir/Ritonavir Once Daily + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject With Suppressed Plasma Viremia
This is an open label randomized clinial trial to evaluate the treatment with darunavir/ritonavir (800mg/100mg) plus lamivudine (300 mg) once daily versus continuing with darunavir/ritonavir (800mg/100mg) once daily plus tenofovir/emtricitabine (300mg/200mg) or abacavir/lamivudine (600mg/300mg) in HIV infected subject with suppressed plasma viremia.
NCT02159599 HIV Infection Drug: Darunavir/Ritonavir Drug: Lamivudine Drug: Emtricitabine/tenofovir or abacavir/lamivudine MeSH:HIV Infections
3. Treatment with darunavir/ritonavir once a day and tenofovir/emtricitabine or abacavir/lamivudine during at least 4 weeks at the moment of the screening 4. Plasma HIV RNA levels below 50 copies / ml for at least 6 months (two separate measurements at least 6 months with viremia <50 copies / ml between both). 5. HbsAg negative Exclusion Criteria: 1. Pregnant or breastfeeding woman 2. Evidence of Lamivudine resistance (any previous genotype with mutation M184V/I or K65R) and/or to darunavir (population genotype show any of the following mutations: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, T74P, L76V, I84V, L89V). --- M184V --- --- K65R --- --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- G73S ---
Primary Outcomes
Description: Undetectable viral load <50 copies/ml according to the FDA snapshot algorithm
Measure: Proportion of patients with undetectable viral load Time: week 48Secondary Outcomes
Description: Undetectable viral load < 50 copies/ml according to the FDA snapshot algorithm
Measure: Proportion of patients with undetectable viral load Time: Week 24Description: Proportion of patients with viral load < 200 copies/ml according to FDA snapshot algorithm
Measure: Proportion of patients with viral load < 200 copies/ml Time: week 48Description: Viral load ≥ 50 copies/ml
Measure: Proportion of patients who present viral load ≥ 50 copies /ml one time Time: From basal visit until week 48 visitDescription: Viral load ≥ 50 copies /ml
Measure: Proportion of patients who present viral load ≥ 50 copies /ml more tan two times Time: From basal visit until week 48 visitDescription: Viral load < 50 copies/ml
Measure: Proportion of patients who maintained viral load < 50 copies/ml in all determinations Time: week 48Description: CD4/µl
Measure: Median of change cells CD4/µl count from basal to week 48 Time: week 48Measure: Median of change in triglycerides , LDL-cholesterol, HDL-cholesterol and total cholesterol from basal to week 48 Time: week 48
Description: Change in glomerular filtration
Measure: Change in renal function Time: week 48Measure: Change in proportion of patients with renal tubular dysfunction Time: week 48
Other Outcomes
Description: Mutations in patients viral failure
Measure: Proportion of genotypic resistance mutations Time: Week 48Measure: Change in proportion of genotypic resistance mutations Time: week 48