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

ABSTRACT

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.

KEYWORDS:

• Cart intensification
• HIV-1 therapeutic vaccine
• HIV-1 Tat
• clinical trials
• anti-Tat antibodies
• proviral DNA
• functional cure
• test and treat
• pediatric clinical trials

Acknowledgments

M. Falchi (NAC, ISS, Rome, Italy) for helpful discussion; A. Arancio, M. Campagna, G. Paniccia (NAC, ISS, Rome, Italy) for laboratory support; F. Cammisa (NAC, ISS, Rome, Italy) for support to study management and editorial assistance;

S. De Menna, S. Tobelli and F. Fedeli (NAC, ISS, Rome, Italy) for administrative support; P. Arciero (NAC, ISS, Rome, Italy) for laboratory support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The manuscript was not funded.