HIV Infection
Conditions
Brief summary
The objective of this study is to clarify whether if starting antiretroviral treatment based on dual therapy (DTG + 3TC) could provide less control of residual HIV replication and, therefore, a detriment on immune activation and inflammation compared to starting with triple therapy, and could worsen the patients' long-term prognosis. For this purpose, the investigator has designed a randomized clinical trial where will assess the immunological recovery (CD4+/CD8+), immune activation, proliferation, senescence and apoptosis in T lymphocytes CD4+ and CD8+ cells by flow cytometry, the immune activation of monocytes/ macrophages and plasma concentrations of various inflammatory mediators by ELISAS, and the thymic function, the cellular reservoir of HIV and the degree of HIV DNA transcription by digital dropped PCR.
Interventions
DRUGRandomize
Randomize to naive-treatment HIV-infected patients to receive dual o triple therapy as initial antiretroviral treatment
Sponsors
Hospitales Universitarios Virgen del Rocío
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treatment-naïve HIV-1-infected patients ≥ 18 years of age. * Plasma HIV-1 RNA \>5000 and \<500.000 copies/ml. * T lymphocyte CD4+ count in peripheral blood \>200/μl. * Patients of childbearing age should consent to use a highly effective contraceptive method from 15 days before the time of inclusion of the study until 30 days after the end of it. It is considered a highly effective method: * Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of Investigational Product, throughout the study, and for at least 2 weeks after discontinuation of all study medications; * Any intrauterine device with published data showing that the expected failure rate is \<1% per year (not all intrauterine devices meet this criterion) * 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. * Any other method with published data showing that the expected failure rate is \<1% per year. * Signed written informed consent prior to inclusion.
Exclusion criteria
* Acute HIV infection * T lymphocyte CD4+ count in peripheral blood ≤ 200/µl * Active opportunistic infection. * Pregnancy at inclusion or during the follow-up * Active hepatitis C and/or B virus co-infection. * ALT ≥ 5 times the 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 (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones). * Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification. * Current or past disease that requires the use subsidiary of treatment with corticosteroids, immunomodulatory agents, interferon or chemotherapeutic agents. * Any laboratory abnormality grade 3 or 4 according to the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (Annex 3) * Concomitant use of drugs with potential major interactions with the prescribed drugs according to the respective full prescribing information. * Estimated creatinine clearance \<50ml/min. * History or presence of allergy to the study drugs or their components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| proviral HIV-DNA | 48 and 96 weeks | Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Activation | 48 and 96 weeks | Mean changes immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T cells. |
| Immune Recovery | 48 and 96 weeks | Mean changes immune recovery assessed by CD4+/CD8+ T cell ratio. |
| Monocytes Activation | 48 and 96 weeks | Mean changes monocytes activation (plasma sCD14 and sCD163). |
| Inflammation | 48 and 96 weeks | Mean changes concentration of pro-inflammatory soluble mediator in plasma: TNF-α, IL-1β, IL-6, IP-10, IFN- γ, MIP-1α, MIP-1β, hsPCR y D-dímers. |
| Viral Reservoir | 48 and 96 weeks | Mean changes viral reservoir size, evaluated by proviral HIV-DNA and HIV-RNA in peripheral blood mononuclear cells (PBMC) and CD4+ T cells isolate. |
| Immunosenescense | 48 and 96 weeks | Mean changes expression of markers for recent thymic emigrants (CD31), proliferation (Ki67), dysfunction (PD-1), senescence (CD57), and apoptosis (annexin A) in both CD4+ and CD8+ T cells. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Semen | 24 weeks | Mean changes of HIV-RNA seminal plasma viral load |
| GALT | 48 weeks | Mean changes of viral reservoir assessed as proviral HIV-DNA and HIV-RNA in GALT |
Countries
Spain
Outcome results
None listed