Implication for Strategies of Long Term Control of Viral Replication in Patient With Primary HIV Infection (PHI).
- Conditions
- HIV-1-infection
- Interventions
- Combination Product: SYMTUZACombination Product: DESCOVY+DOLUTEGRAVIRCombination Product: SYMTUZA+DOLUTEGRAVIR
- Registration Number
- NCT04225325
- Lead Sponsor
- ADRIANO LAZZARIN, MD
- Brief Summary
Multicenter, parallel group, randomised, open label, study. Twenty-five clinical centers constituting the InAction network will participate the study.
Eligible patients will be randomised in a ratio 10:10:8 to be treated with one of the three antiretroviral regimens:
* TDF/FTC 245 mg/200 mg single tablet QD + DRV /cobicistat 800 mg /150 mg single tablet QD (Arm A, standard regimen),
* TDF/FTC 245 mg/200 mg single tablet QD + DTG 50 mg QD (Arm B, standard regimen).
* TDF/FTC 245 mg/200 mg single tablet QD + DRV 800 mg /cobicistat single tablet QD + DTG 50 mg QD (Arm C, experimental regimen).
One-hundred-and-twelve PHI subjects will be recruited for this study among those attending the outpatient Clinic of Infectious Diseases, Ospedale San Raffaele and other Italian centres, involved in the INACTION network.
- Detailed Description
At Screening, potential subjects will perform serology for HIV, ELISA and Western Blot (WB), to assess Fiebig stage:
* Stage I: ELISA negative, WB negative, HIV-1 RNA positive.
* Stage II: ELISA positive for p24, WB negative.
* Stage III: ELISA positive, WB negative.
* Stage IV: ELISA positive, WB undetermined.
* Stage V: ELISA positive, WB partially positive with p31 negative.
* Stage VI: ELISA positive, WB positive, previous HIV negative test within 6 months
On Day 0 (Baseline-BL), within 0-5 days from screening, subjects will:
* perform biochemical and haematological tests, virological test (HIV-1 RNA, tropism test, genotype resistance test), immunological test (CD4+, CD4%, CD8+, CD8%, CD4/CD8).
* Perform anal and nasal brushing
* Perform microbiome
* Have behavioral survey questionnaire administered
* collect an additional sample of blood (80 mL) to perform the following evaluations:
* HIV-DNA
* T cells, B cells and DC subsets
* HLA-A, B and C
* Inflammatory markers
* Pharmacokinetic: Ctrough
* start one of the study treatment according to randomization
* Arm A: TDF/FTC 10 mg/200 mg single tablet QD +DRV /cobicistat 800 mg /150 mg single tablet QD
* Arm B: TDF/FTC 25 mg/200 mg single tablet QD +DTG 50 mg QD
* Arm C: TDF/FTC 10 mg/200 mg single tablet QD +DRV/cobicistat single tablet QD +DTG 50 mg QD
In addition, on Day 0 (Baseline-BL), subjects who will sign an additional specific informed consent:
* cerebrospinal fluid (CSF) will be collected to evaluate HIV-1 RNA
* GALT biopsies will be performed in order to allow the evaluation of viral reservoirs.
* Lymph nodes biopsies to evaluate immunological subset Following Day 0, subjects will return for visits at Weeks 2, 4, 8, 12, 24, 36 and 48 or at discontinuation.
HIV-1 RNA levels will be measured and physical examination will be performed at all the scheduled study visits CD4+, CD4%, CD8+, CD8%, CD4/CD8 will be repeated at Weeks 4, 8, 12, 24, 36, 48 or at discontinuation.
Laboratory safety parameters (complete blood count, renal function, hepatic function, lipids and glucidic profile) will be tested at Weeks 4, 8, 12, 24, 36, 48 or at discontinuation.
At week 12 and 48 or at discontinuation, an additional blood sample of 80 mL will be collected to perform the following evaluations:
* HIV-DNA and viral tropism
* T, B and DC cells subsets
* Inflammatory markers At week 2, 4, 8, 12, 24, 36, 48 or at discontinuation a blood sample of 21 mL will be collected for pharmacokinetic of drugs.
At week 12, 48 or discontinuation a stool sample will be collected to evaluate microbioma.
At week 12 and 48 anal brushing and nasal brushing will be performed to evaluate HIVDNA and pharmacokinetic analysis.
At week 12 and 48 behavioral survey questionnaire will be administered to the patient.
At week 12, or at discontinuation, in subjects who will have signed the specific additional informed consent:
* liquor will be collected to evaluate HIV-1 RNA and drugs concentration in central nervous system.
* CSF will be collected to evaluate HIV-1 RNA and drugs concentration in central nervous system.
* GALT biopsies and lymph nodes biopsy will be performed in order to allow the evaluation of viral reservoirs.
Subjects will complete the study when they will reach week 48 on their assigned regimen. At the end of the study, they will continue assigned treatment in arm A and B; if the study will show a superiority of ARM C, the patients in this arm will continue the regimen. In case of non superiority they will be switch to triple therapy. The last patient visit is the last on-study visit or date of death or lost-to follow-up or discontinuation for any reason, whichever occurs last during the conduction of the study.
Considering that the patients' enrollment will last 96 weeks, the overall length of the trial will be 144 weeks.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 112
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A: SYMTUZA SYMTUZA TAF/FTC 245 mg/200 mg single tablet QD +DRV /cobicistat 800 mg /150 mg single tablet QD B: DESCOVY+DOLUTEGRAVIR DESCOVY+DOLUTEGRAVIR TAF/FTC 245 mg/200 mg single tablet QD+DTG 50 mg QD C: SYMTUZA+DOLUTEGRAVIR SYMTUZA+DOLUTEGRAVIR TAF/FTC 245 mg/200 mg single tablet QD+DRV/cobicistat single tablet QD + +DTG 50 mg QD
- Primary Outcome Measures
Name Time Method the change of total HIV-DNA level from baseline to 48 weeks. 48 weeks The primary objective of the study is to compare the proviral DNA change in patients who started three different antiretroviral treatments.
- Secondary Outcome Measures
Name Time Method change in HIV-1 RNA in CSF week 12 and 48 the change of total copies/mL of HIV-RNA level in cerebrospinal fluid
the proportion of patients with HIV-1 RNA <50 copies/mL weeks 12, 24 and 48 proportion of patients with HIV-1 RNA \<50 copies/mL at week 24 and week 48;
time to achieve undetectable viral load week 12 and week 48 HIV-1 RNA \<50 copies/mL
change in HIV-DNA week 12 and week 48 the change of total copies/mL OF HIV-DNA level from baseline to 48 weeks
Trial Locations
- Locations (1)
Ospedale San Raffaele
🇮🇹Milan, MI, Italy