SNPMiner Trials (Home Page)
Report for Mutation M46I
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 12 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 ---
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 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 ---
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 963 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 ---
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
4 Prevention of HIV1 Mother to Child Transmission Without Nucleoside Analogue Reverse Transcriptase Inhibitors in the Pre-partum Phase. A Multicenter Randomised Phase II/III Open Label Study With a Group of 100 Pregnant Women Receiving Lopinavir/Ritonavir and a Group of 50 Receiving Lopinavir/Ritonavir Plus Zidovudine and Lamivudine. ANRS 135 Primeva
In the pre-partum phase the use of antiretroviral therapy for the mother during the last trimester of pregnancy is mandatory. The use of HAART during pregnancy, usually two nucleosides analogues and a protease inhibitor exposes the mother and the child to cumulate toxicities related to both families. The aim of this study is to assess the use of a boosted protease inhibitor without nucleoside analogue during the pre-partum phase for women with no indication of antiretroviral therapy for their own.
NCT00424814 HIV Infections Drug: Kaletra (lopinavir/ritonavir) Drug: Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine) MeSH:HIV Infections
Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) HIV Infections HIV Infections Recent data from the French perinatal cohort and others indicate that HIV-RNA levels at delivery correlate with risk of transmission among women treated with antiretroviral agents. --- V32I --- --- I47A --- --- I50V --- --- V82A --- --- I84V --- --- L24I --- --- L33F --- --- M46I ---
Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) Inclusion Criteria: Assessed between 20 and 24 months of pregnancy - Pregnancy known before 24 weeks of gestation - Documented HIV-1 infection without indication for ARV therapy - CD4 count above or equal to 350 per mm3 - VL under 30 000 copies per ml - Naïve for PI (except treatment during previous pregnancy) - Informed consent signed Exclusion Criteria: - HIV2 infection or HIV1 group O infection - Any pathology related to pregnancy - Contra-indication to study drugs - Unstable hypertension or diabetes - Known risk of premature delivery - In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,) HIV Infections HIV Infections Recent data from the French perinatal cohort and others indicate that HIV-RNA levels at delivery correlate with risk of transmission among women treated with antiretroviral agents. --- V32I --- --- I47A --- --- I50V --- --- V82A --- --- I84V --- --- L24I --- --- L33F --- --- M46I --- --- F53L --- --- I54M --- --- L63P --- --- A71L --- --- V32I --- --- I47A --- --- I50V --- --- V82A --- --- I84V --- --- L24I --- --- L33F --- --- M46I ---
Primary Outcomes
Measure: Proportion of mother with plasma HIV1 below 200 copies per ml after 8 weeks of treatment Time: W8Secondary Outcomes
Measure: Proportion of women maintained with monotherapy until delivery, Time: deliveryMeasure: Proportion of women with a VL below 50 copies per ml at delivery Time: delivery
Measure: Proportion of women harbouring resistant HIV strains four weeks after delivery Time: W4 post partum
Measure: Concentrations of studied drug in plasma and in cord-blood Time: at delivery
Measure: HIV-1 detection and concentrations of studied drug in vaginal secretion before and after treatment Time: W0, W8 of treatment
Measure: concentrations of studied drugs in the new born gastric fluid, HIV diagnostic in infant (criteria for stopping the trial at second infection) Time: birth
5 A 24-week, Randomized, Open-label, 2-arm Study to Compare the Safety, Efficacy and Tolerability of Invirase® Tablets With Ritonavir Versus Kaletra® Tablets in HIV 1 Infected Adults on a Kaletra® Based Regimen With 2 Nucleosides/Nucleotides
This study will compare the benefit for patients switching from Kaletra® to Invirase® tablets over remaining on Kaletra® (based on randomization), to elicit the lipid benefits inferred in previous studies
NCT00438152 HIV Infections Drug: Saquinavir (Invirase®) Drug: Lopinavir/ritonavir (Kaletra®) MeSH:HIV Infections
- Ability and willingness to provide written informed consent and adhere to the study regimen - Females of childbearing potential must have a documented negative serum or urine pregnancy test at screening/baseline and ensure that 2 reliable forms of contraception are being used, including a barrier method, for the duration of the study and for 90 days after the last dose of study medication Exclusion Criteria: - Documented virological failure on a protease inhibitor ARV regimen prior to commencing Kaletra® regimen - Documented protease mutation (one or more from the following list) prior to commencing Kaletra® regimen: - M46I/L/V, I47A/V, G48V/M, I50V, F53L/Y, I54L/M/V/A/T/S, V82A/T/S/F/M/L, I84A/V/C, L90M - Patients with acute hepatitis B or C infection - Females who are pregnant, breast-feeding, or who plan to become pregnant or breast-feed during the study· - Significant renal dysfunction (creatinine clearance [CrCl] <60 mL/min) and/or hepatic impairment (aspartate aminotransferase/alanine aminotransferase [AST/ALT] >3 X ULN and/or documented liver cirrhosis) Note: The site will calculate each patient's CrCl using the Cockcroft-Gault formula [28] as shown below: CrCl = [140 - age (yr)] × weight (kg) × constant 72 × serum creatinine (Cr) (mg/dL) where, constant = 1 for men and 0.85 for women - Any current known clinical or laboratory parameter of ACTG Grade 4 (see Appendix 4). --- M46I ---
Primary Outcomes
Measure: To evaluate the lipid benefits of Invirase® tablets with ritonavir versus Kaletra® tablets in HIV-1 infected adults on an antiretroviral regimen containing Kaletra® with two nucleosides/nucleotides Time: 24 weeksSecondary Outcomes
Measure: To evaluate the efficacy of Invirase® tablets with ritonavir versus Kaletra® tablets in HIV-1 infected adults on an ARV regimen containing Kaletra® with 2 nucleosides/nucleotides. Time: 4 weeks, 12 weeks and 24 weeks.Measure: To evaluate additional safety and tolerability of Invirase® tablets with ritonavir versus Kaletra® tablets in HIV-1 infected adults on an antiretroviral regimen containing Kaletra® with 2 nucleosides/nucleotides. Time: Week 24
6 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 ---
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
7 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 ---
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
8 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 ---
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 days9 A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose-response of TMC114/RTV in 3-class-experienced HIV-1 Infected Subjects, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.
The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir
NCT00650832 HIV Drug: TMC114; darunavir; Prezista
Inclusion Criteria: - Patients with documented HIV-1 infection - Patients receiving a PI-containing regimen at screening initiated at least 8 weeks prior to screening with plasma HIV-1 RNA > 1000 copies/mL - Prior use of more than 1 NRTI for at least 3 months in total - Prior use of one or more NNRTIs (investigational included) as part of a failing regimen - Patients having at least 1 primary PI mutation at screening as defined by the IAS guidelines (D30N, M46I/L, G48V, I50V/L, V82A/F/T/S, I84V, L90M)16 - patients experienced to at least one PI for a total period of at least 3 months - Patients voluntarily signs the informed consent form - Patients can comply with the protocol requirements - Patients having a general medical condition that, in the investigator's opinion, does not interfere with the assessments and the completion of the trial. --- D30N --- --- M46I ---
Primary Outcomes
Measure: The primary objective of the trial is to compare all TMC114/RTV dose groups with control at Week 24 (the primary endpoint) by means of the confirmed virologic response, defined as a drop in viral load of at least 1 log10 versus baseline.Secondary Outcomes
Measure: To evaluate safety and tolerability over 24 to 144 weeks; To evaluate the durability of the antiviral activity; To investigate the dose-response by comparing the different TMC114/RTV dosages.10 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 ---
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 9611 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 ---
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
12 A Pilot Trial Evaluating Maintenance Therapy With Lamivudine(Epivir®) and Dolutegravir(Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple HAART - ANRS 167 Lamidol
The principal objective is to evaluate the antiviral efficacy of 48 weeks treatment with the two-drugs combination dolutegravir(Tivicay®) and lamivudine(TEpivir®) in HIV-1 infected patients virologically suppressed with triple HAART.
NCT02527096 HIV-1 Infection Drug: dolutegravir (Tivicay®) - Phase 1 Drug: lamivudine (Epivir®) - Phase 2 Drug: dolutegravir (Tivicay®) - Phase 2 MeSH:Acquired Immunodeficiency Syndrome HIV Infections
Inclusion Criteria: - HIV-1 infected patient - Age ≥ 18 years - CD4 cell count nadir > 200/mm3 - Genotype on pre-HAART interpreted with the last version of the ANRS AC11 resistance group's algorithm which presents: - no major mutation on protease among: D30N, V32I, M46I/L, I47A/V, G48V, I50L/V, 154M/L, L76V, V82A/F/T/S, I84V, N88D/S, L90M,- no mutation on RT (except the mutation A98S if the patient is not infected by the virus subtype C), - no mutation on integrase (if the genotype is available), - First-line treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, 1 NNRTI or 1 INI). --- D30N --- --- V32I --- --- M46I ---
Primary Outcomes
Description: Virological failure is defined by plasma HIV RNA > 50 cp/mL on 2 following samples at 2 to 4 weeks apart.
Measure: Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis) Time: from week 8 to week 56 (± 4 weeks)Secondary Outcomes
Description: Evaluation was calculated as the CD4 count at the corresponding week minus the baseline CD4 count
Measure: Evolution of CD4 and CD8 lymphocytes count (analysis) Time: from week 8 to week 32 and week 56Measure: Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis) Time: week 56
Measure: Profile of resistance mutations in plasma in case of virological failure Time: week 56
Measure: Percentage of participants with plasma HIV RNA < 1 cp/mL Time: Day 0, week 8, week 32 and week 56
Description: Influence of total DNA at Day 0 on the occurrence of virological failure or blip
Measure: Influence of total DNA on the occurrence of virological failure or blip Time: from Day 0 to week 56Measure: Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip Time: week 56
Measure: Measure of adherence to treatment (self-reported) Time: Day 0, week 4, week 8, week 32 and week 56
Measure: Measure of quality of life (self-reported) Time: Day 0, week 8 and week 56
Description: Evaluation of medico-economic aspects. Evaluate the direct medical cost related to dolutegravir and lamivudine versus the cost of the previous treatment.
Measure: Comparison of Medico-economic substudy (analysis) Time: week 56Description: Measure of concentrations of dolutegravir and NRTI, and HIV RNA in semen at Week 8 and Week 32 in a subgroup of 20 participants
Measure: Sperm substudy measure of concentration Time: Week 8 and week 32