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Report for Clinical Trial NCT01423812

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

DRIVESHAFT : Darunavir/Ritonavir In Virologically-suppressed Experienced Subjects Halving an Antiretroviral by Finetuning Therapy - A Phase IV Randomized, Open-Label Study to Evaluate in HIV-1 Infected , Virologically-suppressed Patients on Regimens With Darunavir 600mg/ Ritonavir 100mg Twice-daily Switching to Darunavir 800mg/ Ritonavir 100mg Once-daily Versus Continuing Darunavir 600mg/ Ritonavir 100mg Twice-daily Containing Regimens

Darunavir is a nonpeptidic protease inhibitor with a high genetic barrier to resistance that evolved from a prototype compound synthesized using structure-based design strategies. Once-daily darunavir at 800mg boosted with 100mg of ritonavir is an effective antiretroviral agent indicated for HIV-infected treatment-naïve patients. In treatment-experienced patients, darunavir was initially approved for twice-daily administration boosted with twice-daily ritonavir at 600mg and 100mg, respectively. Recently, once-daily darunavir/ritonavir was approved for use in treatment-experienced adult patients with viremia with no darunavir resistance mutations. In treatment-experienced patients with viral suppression, switching from an antiretroviral taken twice-daily to a once-daily dose is an attractive option to promote greater patient acceptability and adherence, and potentially minimize side effects and toxicities. Because of darunavir/ritonavir's high genetic barrier to resistance and well-established safety profile at a once-daily dose, switching patients with virologic suppression from twice-daily darunavir/ritonavir to once-daily darunavir/ritonavir will likely confer attributes more favorable to patients through a simplified dosing schedule and lower potential for lipid elevation without the loss of virologic control. DRIVESHAFT is a 48-week Phase 4, randomized, open label, comparative study. The study will be conducted in 60 HIV-1 infected, antiretroviral experienced, virologically-suppressed patients on regimens containing darunavir 600mg/ ritonavir 100mg twice-daily and a minimum of two other antiretrovirals, with a history of 0-1 darunavir-associated resistance mutations. Subjects will be randomized 1:1 to switch to darunavir 800mg/ ritonavir 100mg once-daily or continue on their current regimen. Rates of virologic suppression of once-daily darunavir/ritonavir regimens relative to darunavir/ritonavir twice-daily regimens will be compared, and safety, change from baseline fasting lipid parameters, and adherence will be evaluated.

NCT01423812 HIV

2 Interventions

Name: Twice-daily Darunavir and ritonavir

Description: Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily
Type: Drug
Group Labels: 1

Twice-daily Darunavir and ritonavir

Name: Once-daily Darunavir and ritonavir

Description: Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks
Type: Drug
Group Labels: 1

Once-daily Darunavir and ritonavir


Primary Outcomes

Description: Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using a Missing, Switch, or Discontinuation = Failure (MSDF) algorithm as codified by the FDA's "snapshot" algorithm

Measure: Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects

Time: 48 weeks after randomization to study medication

Secondary Outcomes

Description: Proportion of subjects with plasma HIV-1 RNA <50 c/mL and <400 c/mL at Week 24 Proportion of subjects with plasma HIV-1 RNA <400 c/mL at Week 48

Measure: Secondary Efficacy Endpoints

Time: Within 48 weeks after randomization to study medication

Description: •Compare the tolerability, safety, and change in lipid parameters(total cholesterol, LDL, HDL, triglycerides) of once-daily versus twice-daily darunavir/ritonavir containing regimens over 48 weeks

Measure: Safety Assessment

Time: Within 48 weeks of randomization to study medications

Description: •Absolute values and changes from baseline in CD4+ and CD8+ over time

Measure: Immunologic Endpoints

Time: 48 weeks after randomization to study medications

Description: •Assess the development of viral resistance in subjects experiencing virological failure

Measure: Assessment of Virologic Failure

Time: Within 48 weeks of randomization to study medications

Description: Characterize adherence to once-daily versus twice-daily darunavir/ritonavir containing regimens using the Modified Medication Adherence Self-Report Inventory (M-MASRI) scale

Measure: Medication Adherence Assessment

Time: Within 48 weeks of randomization to study medications

Description: •Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24

Measure: Secondary Efficacy Endpoints

Time: week 24

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 10 SNPs

SNPs


1 I47V

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V ---


2 I50V

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V ---


3 I54L

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L ---


4 I84V

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V --- --- I84V ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V --- --- I84V ---


5 L33F

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F ---


6 L76V

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V ---


7 L89V

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V --- --- I84V --- --- L89V ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V --- --- I84V --- --- L89V ---


8 T74P

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P ---


9 V11I

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I ---


10 V32I

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis Inclusion Criteria: 1. ART-experienced, HIV-1 infected subjects ≥18 years of age. 2. A female subject is eligible to enter and participate in the study if she: 1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, 2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy: - Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications. --- V11I --- --- V32I ---

3. CD4 >50 cells/mm3 4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen 5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals 6. Negative serum pregnancy test at screening visit Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Known hypersensitivity reaction to agents being utilized in the study 2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype 3. Pregnant or breast feeding woman 4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis HIV null --- V11I --- --- V32I ---



HPO Nodes