Immune Therapy and Analytical Treatment Interruption in HIV+ Participants Who Received an Allogeneic Stem Cell Transplantation (ITATI)

The availability of antiretroviral therapy (cART) for HIV-1 infection has led to a reduction in morbidity in patients with chronic HIV infection. However, cART does not eliminate HIV-1 that persists as a latent infection in cellular reservoirs. Usually, HIV viremia rapidly rebounds if antiretroviral therapy is interrupted. Consequently, HIV infected individuals must commit to expensive, life-long therapies and must tackle problems associated with chronic infection and uninterrupted cART, including continuous clinical and laboratory monitoring, drug toxicities, and chronic immune activation/inflammation.

Currently, there is an emerging interest in developing safe and affordable curative strategies that would eliminate the need for lifelong therapy. However, to date only allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown results in decreasing the HIV-1 reservoirs.

The IciStem Consortium (www.icistem.org) has assembled the largest and most exhaustive observational cohort for the study of HIV reservoir dynamics in allo-HSCT HIV+ individuals with severe hematological malignancies worldwide. Within the cohort, only individuals transplanted with a donor with thw CCR5A32 mutation have shown signs of HIV remission. On the other side broadly neutralizing antibodies (bNAbs) have shown the potential to control HIV infection. This study intends to evaluate if the allo-HSCT combined with the additional application of bNAbs is effective to control HIV replication.

Detailed Description:

The implementation of highly effective, convenient, and well-tolerated combination antiretroviral therapy (cART) for HIV-1 infection has substantially reduced AIDS-related morbidity and mortality. However, cART does not eliminate HIV-1 that persists as a latent infection in cellular reservoirs, including resting memory CD4+ T cells, leading to an underlying raised state of immune activation and subsequent immune senescence. Of note, HIV viremia rapidly rebounds if antiretroviral therapy is interrupted. Consequently, HIV infected individuals must commit to expensive, life-long therapies and must tackle problems associated with chronic infection and uninterrupted cART, including continuous clinical and laboratory monitoring, drug toxicities, and chronic immune activation/inflammation. Therefore, there is an emerging interest in developing safe and affordable curative strategies that would eliminate the need for lifelong therapy while improving the health of infected subjects and reducing the risk of viral transmission to uninfected individuals. So far, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only intervention to date that systematically reduces HIV-1 reservoirs to undetectable levels regardless of the CCR5Δ32 donor status.