"cART intensification by the HIV-1 Tat B clade vaccine: progress to phase III efficacy studies".

Introduction: In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed.

Areas Covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA). Vaccination with clade-B Tat induced cross-clade neutralizing antibodies, immune restoration, including CD4 T cell increase particularly in low immunological responders, and reduction of proviral DNA. Phase III efficacy trials in SA are planned both in adult and pediatric populations.

Expert Commentary: We propose the Tat therapeutic vaccine as a pathogenesis-driven intervention that effectively intensifies cART and may lead to a functional cure and provide new perspectives for prevention and virus eradication strategies.