Implication for strategies of long term control of viral replication in patient with primary HIV infection (PHI) treated with multitarget antiviral therapy (MT-ART)

Phase 1

• Conditions: subject whith PHI never treated; MedDRA version: 20.1Level: PTClassification code 10000807Term: Acute HIV infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2017-000554-19-IT
• Lead Sponsor: OSPEDALE SAN RAFFAELE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-05
• Last Update Posted: 26 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

-Subjects must be at least 18 years of age at the time of randomization, of either sex and of any race.
-Primary HIV Infection defined according to Fiebig’s classification.
-Subjects must have given written informed consent and must be able to adhere to dose and visit schedules.
-Female subjects of child-bearing potential must agree to use a medically accepted method of contraception.
-Female subjects of child-bearing potential must have a negative serum beta-hCG pregnancy test at Screening, and a negative urine beta-HCG pregnancy test on Day 1 prior to dosing.
A female, may be eligible to enter and participate in the study if she:
ais of non-child-bearing 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;
a.is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
•Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
•Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
•Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see Appendix 4 for an example listing of approved IUDs);
•Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject;
•Approved hormonal contraception for subjects randomized to arm B (TDF/FTC + DTG) (see Appendix 4 for a listing of examples of approved hormonal contraception)
•Approved hormonal contraception and a barrier method for subjects randomized to arm A (TDF/FTC +DRV/cobicistat) and C (TDF/FTC +DRV/cobicistat +DTG)
•Any other method with published data showing that the expected failure rate is <1% per year.
Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IP. Approved hormonal contraception for subjects randomized to the treatment groups should be specified.

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 107
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

-Female subjects of childbearing potential who are breastfeeding, pregnant, or planning to become pregnant.
-Subjects with active opportunistic infection or malignancy.
-Subjects positive for Hepatitis B at screening (HBsAg+), or anticipated need for Hepatitis C virus (HCV) therapy during the study.
-Subjects with known liver cirrhosis.
-Subjects with any clinically significant condition or situation other than the condition being studied that, in the opinion of investigator, would interfere with the study evaluations or optimal participation.
-Subjects with allergy/sensitivity to drugs or its excipients.
-History or presence of allergy to the study drugs or their components
-Alanine aminotransferase (ALT) ¿5 times the upper limit of normal (ULN), OR ALT ¿3xULN and bilirubin ¿1.5xULN (with >35% direct bilirubin)
-Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
-Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
-Subject has creatinine clearance of <70 mL/min via Cockroft-Gault method
-Hepatic failure (Child-Plug grade C)
-Use of not modifiable concomitant drugs: carbamazepine, fenitoine, fenobarbital, rifampicine, Hypericum perforatum, dofelitide.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary end point will be the change in total HIV-DNA level from baseline to 48 weeks;Secondary Objective: •long-term virological efficacy;<br>•safety;<br>•viral reservoirs: HIVDNA in PBMC, anal brushing, nasal brushing and HIVRNA in cerebrospinal fluid (CSF) ;<br>•pharmacokinetic (Ctrough) on plasma and PBMC, anal and nasal brushing and cerebrospinal fluid (CSF), lymph nodes and GALT; <br>•genetic markers: HLA-A, HLA-B, HLA-C;<br>•variation in immunological parameters;<br>•variation in inflammation and immune-activation markers;<br>•variation in T-cells, B-cells and DC-phenotypes;<br>•variation of viral tropism.<br><br>;Primary end point(s): The primary end point will be the change in total HIV-DNA level from baseline to 48 weeks.;Timepoint(s) of evaluation of this end point: 48 WEEKS