Implication for Strategies of Long Term Control of Viral Replication in Patient With Primary HIV Infection (PHI) Treated With Multitarget Antiviral Therapy (MT-ART)
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- the change of total HIV-DNA level from baseline to 48 weeks.
研究概览
简要总结
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.
详细描述
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:
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perform biochemical and haematological tests, virological test (HIV-1 RNA, tropism test, genotype resistance test), immunological test (CD4+, CD4%, CD8+, CD8%, CD4/CD8).
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Perform anal and nasal brushing
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Perform microbiome
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Have behavioral survey questionnaire administered
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collect an additional sample of blood (80 mL) to perform the following evaluations:
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HIV-DNA
-
T cells, B cells and DC subsets
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HLA-A, B and C
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Inflammatory markers
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Pharmacokinetic: Ctrough
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start one of the study treatment according to randomization
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •is 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;
- •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)
- •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.
排除标准
- •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.
研究组 & 干预措施
B: DESCOVY+DOLUTEGRAVIR
TAF/FTC 245 mg/200 mg single tablet QD+DTG 50 mg QD
干预措施: DESCOVY+DOLUTEGRAVIR (Combination Product)
C: SYMTUZA+DOLUTEGRAVIR
TAF/FTC 245 mg/200 mg single tablet QD+DRV/cobicistat single tablet QD + +DTG 50 mg QD
干预措施: SYMTUZA+DOLUTEGRAVIR (Combination Product)
A: SYMTUZA
TAF/FTC 245 mg/200 mg single tablet QD +DRV /cobicistat 800 mg /150 mg single tablet QD
干预措施: SYMTUZA (Combination Product)
结局指标
主要结局
the change of total HIV-DNA level from baseline to 48 weeks.
时间窗: 48 weeks
The primary objective of the study is to compare the proviral DNA change in patients who started three different antiretroviral treatments.
次要结局
- change in HIV-1 RNA in CSF(week 12 and 48)
- the proportion of patients with HIV-1 RNA <50 copies/mL(weeks 12, 24 and 48)
- time to achieve undetectable viral load(week 12 and week 48)
- change in HIV-DNA(week 12 and week 48)
研究者
ADRIANO LAZZARIN, MD
HEAD OF INFECTIOUS DISEASES CLINIC
Ospedale San Raffaele