Treatment With MSC in HIV-infected Patients With Controlled Viremia and Immunological Discordant Response

This is a phase I-II, randomised, placebo-controlled, clinical trial, currently ongoing in a single Spanish hospital (Hospital Virgen del Rocío, Seville), to evaluate the safety and feasibility of a 4-doses treatment regimen with MSCs (1 million cells/Kg MSCs, weeks 0-4-8-20) in HIV infected adults with swith discordant virological and immunological response to antiretroviral therapy. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 15 days, receiving unblinded cell therapy. In the second phase of the trial, subjects are block randomised (1:1) to receive either MSCs (n=5), or placebo (n=5), as the control treatment. Immune response variables, adverse events, opportunistic infection signs are evaluated as determinants of safety and efficacy of MSCs. Study endpoints are measured along a follow-up period of 24 months, that includes 17 visits according to a decreasing frequency rate. Intention to treat, and per protocol, and safety analysis will be performed.

Inclusion criteria

• Confirmed HIV infection
• Age> 18 years, both sexes
• In treatment with antiretroviral therapy (ART)
• Sustained HIV viral load <50 copies / ml for ≥ 1 years prior to study entry
• CD4 + cell count < 350/mL
• Immunological discordant response defined as: an increase <75 or <150 in CD4+ cell counts within one or two years of undetectable viraemia, respectively; or CD4 + cell count <350/mcl after 3 years of ART and undetectable viraemia (<50 copies/ml) ≥ 1 year
• Writen informed consent
• In women of child bearing potential or her partners:commitment to use contraceptive method of proved efficiency throughout the duration of the clinical trial

Exclusion criteria

• Pregnancy, breastfeeding, or refusal to the use of contraceptive methods
• Opportunistic infections in the last 12 months prior to study entry
• Active co-infection with hepatitis B virus/hepatitis C virus
• Child Pugh's scale stage C cirrhosis of the liver of any a aetiology
• Portal hypertension and / or hypersplenism of any aetiology
• Malignant neoplasia
• Treatment with steroids, immunomodulators, interferon, chemotherapy or any other medicinal product that could modify the number of CD4+ within the last 12 months prior to study entry
• Confirmed analytical 3 or 4 grade (AIDS Clinical Trials Group scale) abnormalities