There are 4 clinical trials

Clinical Trials

1 Prospective Clinical Trial to Assess Safety and Efficacy of DRV/r(TMC 114/r), ETV(TMC 125) and MK-0518 in Addition to OBT in HIV-1 Infected Patients With Limited to No Treatment Options ANRS 139 TRIO

The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: darunavir, etravirine and MK-0518 (raltegravir) in patients who have multi-resistant viruses and limited treatment options. An optimized background regimen that may include nucleoside reverse transcriptase inhibitors (NRTIs) and enfuvirtide can be added, if possible, to this combination. Patients will undergo treatment for 48 weeks and virological efficacy will be evaluated at week 24.

NCT00460382 HIV Infections Drug: raltegravir potassium Drug: darunavir/ritonavir Drug: etravirine Drug: Optimized background regimen

MeSH:HIV Infections

- Genotypic resistance testing at the screening visit: - Protease inhibitor mutations: over or equal to 3 primary protease inhibitor mutations among: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54M, L76V, V82A/F/L/T/S, I84V, N88S and L90M (IAS list 2006) but below or equal to 3 mutations among the following: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V et L89V (virus sensitivity to darunavir/ritonavir). - Reverse transcriptase mutations: over or equal to 3 NRTI mutations (among IAS list) and below or equal to 3 mutations among: A98G, L100I, K101Q/P/E, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V/C/H/L, Y188C/H/L, G190A/C/E/Q/S, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F (virus sensitivity to etravirine) Exclusion Criteria: - Non effective barrier contraception in women of child bearing potential - Pregnant women or women who are breastfeeding - Opportunistic infection at the acute phase - Decompensated cirrhosis (stage B or C of Child-Pugh score) - Malignancy requiring chemotherapy or radiotherapy - Contraindicated medications being taken by the patient (listed in protocol) - Allergy to the active substances and expedients of darunavir, etravirine and raltegravir. --- D30N --- --- V32I --- --- L33F --- --- M46I --- --- I47A --- --- G48V --- --- I50L --- --- I54M --- --- L76V --- --- V82A --- --- I84V --- --- N88S --- --- L90M --- --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- G73S --- --- L76V --- --- I84V --- --- L89V --- --- A98G --- --- L100I --- --- K101Q --- --- K103H --- --- V106A --- --- V108I --- --- E138G ---

2 A Phase IV, Open-label Single-arm Study Investigating the Pharmacokinetics and Pharmacodynamics of the Antiretroviral Combination of Rilpivirine and Ritonavirboosted Darunavir in Therapy-naive HIV-1 Infected Patients.

For patients who are starting to take antiretroviral medication (to treat HIV) for the first time, there are now a variety of different medicines which may be taken together as a combination in order to form an effective treatment which suppresses the virus for prolonged periods of time. Currently, national guidelines recommend the use of two different drugs of one type (the nucleoside/ nucleotide reverse transcriptase inhibitors, NRTI often known as "nukes") with a third drug from one of two other types (either a nonnucleoside reverse transcriptase inhibitor, known as an NNRTI or "nonnuke", or a protease inhibitor, known as a PI) to form a treatment regime of three active drugs. In the UK and Europe, all PIs are given in combination with a small dose of a second PI, ritonavir, which has the effect of boosting the levels of the active PI in the bloodstream. The investigators know from both research studies and patient experience in clinic that a combination of a ritonavirboosted PI with an NNRTI achieves similar results in suppressing the HIV virus, compared to the use of either a PI or NNRTI with 2 NRTI as described above. In this study, the investigators will observe the combination of two licensed antiretroviral medications, ritonavirboosted darunavir(DRV/r) and rilpivirine (RPV), in suppressing virus when given to patients who are commencing treatment for HIV infection for the first time. Both of these drugs are licensed for treatment of patients with HIV in the UK and Europe, and are currently in standard clinical use. The study will monitor this treatment over the first 48 weeks. The investigators will also examine the levels of both drugs in the bloodstream during the first 4 weeks of starting this regimen, to confirm that they remain at levels which the investigators know to be effective against the virus.

NCT01736761 HIV Drug: Darunavir, Ritonavir and Rilpivirine

- Disallowed concomitant medication as per the summary of product characteristics for darunavir or rilpivirine (see section 5.2). - Any genotypic resistance mutations on screening or prior tests to darunavir (V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V) or rilpivirine (K101E, K101P, E138A, E138G, E138K, E138R, E138Q, V179L, Y181C, Y181I, Y181V, H221Y, F227C, M230I, and M230L). --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54M --- --- I54L --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- K101E --- --- K101P --- --- E138A --- --- E138G ---

3 Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning, ESCAPE Study

This study will evaluate the effects of switching Atripla to Eviplera on neurocognition measured by neuropsychological testing and functional MRI

NCT02308332 Neurocognitive Decline HIV Associated Neurocognitive Disorder Drug: Eviplera

MeSH:Neurocognitive Disorders

Differences in mean changes between baseline and end of study, as well as between the two study groups will be calculated using a paired T-test.. Inclusion Criteria: - Male, between 30 and 50 years - HIV-1 RNA < 50 copies/mL on screening visit - on Atripla continuously for ≥6 months preceding the screening visit - Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y - Negative TPHA or VDRL < 12 months prior to the screening visit - no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. --- K65R --- --- K101E --- --- E138G ---

Inclusion Criteria: - Male, between 30 and 50 years - HIV-1 RNA < 50 copies/mL on screening visit - on Atripla continuously for ≥6 months preceding the screening visit - Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y - Negative TPHA or VDRL < 12 months prior to the screening visit - no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. --- K65R --- --- K101E --- --- E138G ---

4 A Phase IV 48 Week, Open Label, Pilot Study of Darunavir Boosted by Cobicistat in Combination With Rilpivirine to Treat HIV+ Naïve Subjects (PREZENT)

Current HIV treatment guidelines recommend the use of triple-drug therapy (two nucleoside reverse transcriptase inhibitors and either a protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or an integrase inhibitor) for the treatment of antiretroviral (ARV)-naïve patients. With the introduction of highly active antiretroviral therapy (HAART), patients with HIV are living much longer. With the increasing lifespan of persons with HIV, long-term complications from therapy as well as the occurrence of co-morbidities with aging have prompted HCPs to re-think the current treatment paradigm and consider novel combinations of ARVs. All of the currently approved HIV antiretrovirals have been implicated in causing long-term toxicities; however the greatest body of evidence for long-term metabolic effects has implicated the nucleoside reverse transcriptase (NRTI) class. By utilizing a non-NRTI treatment regimen, it is hypothesized that many of these long-term metabolic effects (renal toxicity, bone loss, body fat changes) can be delayed or avoided altogether. The clinical data on novel combinations is currently limited but rapidly growing and has included several combinations that have utilized darunavir. This study will be the first of its kind using the unique combination of darunavir/cobicistat and rilpivirine. Currently, this drug combination is not a recommended option for first time treatment of HIV

NCT02404233 HIV Positive Drug: darunavir/cobicistat Drug: rilpivirine

MeSH:HIV Seropositivity

Exclusion Criteria 1. Patient with active AIDS-defining opportunistic infection or disease according to the 1993 CDC AIDS surveillance definition (Clinical Category C) in the 30 days prior to baseline and that, in the opinion of the investigator, would preclude the patient from participating in the study (See Appendix C). 2. Patient has none of the following darunavir-associated RAMs: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V 3. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e. at least one of the NNRTI rams from the following list; K101E, K101P, E138A, E138G, E138K, E138R, E138Q, , V179L, Y181C, Y181I, Y181V, Y188L, H221Y, F227C, M230I, M230L, or the combination of the K103N and L100I. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- K101E --- --- K101P --- --- E138A --- --- E138G ---

HPO Nodes