Randomized study in patients with chronic HIV infection.

Phase 1

• Conditions: HIV chronic infection; MedDRA version: 17.0Level: LLTClassification code 10001509Term: AIDSSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2014-000515-14-ES
• Lead Sponsor: Fundación SEIMC-GESIDA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-04
• Last Update Posted: 17 May 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Consent to participate in the study, signing and dating the informed consent.
2. HIV patients > 18 years old.
3.Receiving DRV/r qd + TDF/FTC (or ABC/3TC) for at least 4 weeks.
4.Plasma HIV RNA < 50 cop/ml for at least 6 months (2 tests separated at least 6 months with viremia < 50 cop/ml between both determinations).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 256
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 256

Exclusion Criteria

1.HIV pregnant or breastfeeding women.
2.Evidence of resistance to 3TC (any previous genotype with M184V/I mutation) and/or Darunavir (poblational genotype with demonstration of any of these mutations: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, T74P, L76V, I84V, L89V).
3.History of virologic failure (two consecutive viral loads of 200 cop/mL) while the patient was receiving 3TC or FTC, with the following exceptions:
- Exclusion criteria will not be considered if the genotype performed in the moment of the virologic failure does not demonstrate resistance to 3TC and Darunavir (see exclusion criteria 1).
- Exclusion criteria will not be considered in absence of genotype if after the episode a viral load <50 cop/mL is maintained with a treatment composed of 3TC or FTC + 1 nucleoside + 1 non-nucleoside.
4.History of withdrawal for treatments including 3TC or FTC, with the following exception:
- Viral load prior to withdrawal was <50 cop/mL, followed by reintroduction of the same treatment or other treatment including 3TC or FTC + 1 nucleoside + 1 non-nucleoside showing maintenance of viral load <50 cop/mL.
5. Previous dual therapy or monotherapy with 3TC or FTC.
6. Previous dual therapy or monotherapy with a protease inhibitor finalized due to virologic breakthrough, when a genotype resistance test is not available after the virologic breakthrough which allows to discard resistance mutations to any of the drugs.
7. Use of not allowed concomitant medications.
8.Active diseases including opportunistic infections that can difficult the participation in the trial.
9.Any of the following: Hemoglobin <8.0 g/dL, neutrophils <750 cel/microL, platelets <50.000 cel/mm3, creatinine > or = 1.5 times upper limit.
10.Any analytical or clinical event that could jeopardize the patient's safety.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare safety and efficacy of the dual combination DRV/r qd + 3TC qd versus triple therapy with DRV/r qd + TDF/FTC (or ABC/3TC) in HIV-infected patients who have maintained at least six months of viral suppression while receiving triple therapy with DRV/r qd + TDF/FTC (or ABC/3TC).;Secondary Objective: To evaluate the safety and tolerability of the dual and triple combinations.<br>To evaluate the incidence and type of resistance mutations in patients suffering virologic failure.;Primary end point(s): Proportion of patients with HIV-RNA levels below 50 HIV-RNA copies/ml by intention to treat analysis (FDA snapshot algorithm) at week 48.;Timepoint(s) of evaluation of this end point: 48 weeks

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 24 weeks<br>48 weeks;Secondary end point(s): 1.Proportion of patients with HIV-RNA levels below 50 HIV-RNA copies/ml by intention to treat analysis (FDA snapshot algorithm) at week 24<br>2.Proportion of patients with HIV-RNA levels below 200 HIV-RNA copies/ml by intention to treat analysis (FDA snapshot algorithm) at week 48<br>3.Proportion of patients with virologic failure at week 48. <br>4.Percentage of patients with resistance development at week 48<br>5.Median changes in CD4 cell counts<br>6.Incidence of adverse events and incidence of drug discontinuation due to toxicity or intolerance.<br>7.Median changes in triglycerides, total, LDL- and HDL-cholesterol <br>8.Changes in eGFR<br>9.Changes in proportion of patients with renal tubular dysfunction<br>10. Proportion of resistance genotypic mutations in patients showing virologic failure at week 48.<br>11. Description and frequency of resistance genotypic mutations.