Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease
Abstract
:1. Introduction
2. Role of Tat in the Virus Life Cycle
3. Role of Extracellular Tat
4. Role of Extracellular Tat in HIV Reservoir Maintenance and Residual Disease upon Effective cART
5. Anti-Tat Antibodies Protect from Disease Progression
5.1. Naturally Occurring Anti-Tat Antibodies
5.2. Vaccine-Induced Anti-Tat Abs
5.2.1. Vaccination of Nonhuman Primates with Tat or Tat/Env
5.2.2. Phase I Preventive Clinical Trials with Tat or Tat/Env
5.2.3. Phase I Therapeutic Clinical Trials with Tat
5.2.4. Phase II Therapeutic Clinical Trials with Tat in Italy and South Africa
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Reference | |
---|---|
It is detected in cell-free virion | [18] |
It is detected in infected cells prior to virus integration | [19] |
It is released extracellularly in the absence of cell death or cell permeability changes | [20,21] |
Initiates reverse transcription (RT) | [22] |
Increases the rate of transcription | [23] |
Promotes transcription elongation | [24] |
Contributes in splicing regulation | [25] |
Enhances virion infectivity | [26,27] |
Amplifies stochastic basal transcriptional fluctuations at the HIV LTR promoter (the Tat circuitry), establishing active or latent infection, or the reactivation of latent HIV | [13,14,15,16,17] |
Study Code | Volunteers Number | Status | Results | Potential Clinical Benefit |
---|---|---|---|---|
ISS OBS T-003 [117] | 73 | naïve to cART |
| Prevention of progression |
OBS-IFO [118] | 29 | starting cART |
| Improved time-to-response to therapy |
ISS OBS T-002 | 127 | on cART |
| Therapy intensification |
Reference Study | [136] | [137] | [138] |
---|---|---|---|
HIV reservoir measure | Total HIV DNA | Total HIV DNA | Integrated DNA |
cART duration before enrolment | 6 years (mean) | ≥ 5 years | ≥2 years * |
Vaccination | Tat vaccine | None | None |
cART continuation through the study | Yes | Yes | Yes |
Proviral DNA decay: estimated half-life | |||
All patients | 2–3 years | 12 years | NA |
Persistent virological suppression (VL = 0) | 1 year | 7 years | >7 years |
Residual viremia (≥1≤40 RNA copies/mL) | 3 years | 12 years | NA |
Viremic blips (≥40 RNA copies/mL) | 4 years | 22 years | NA |
Proviral DNA decay: estimated time to eradication | Total body reservoir | Total body reservoir | Total blood reservoir |
Persistent virological suppression (VL = 0) | 31 years | NA | >200 years |
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Cafaro, A.; Tripiciano, A.; Picconi, O.; Sgadari, C.; Moretti, S.; Buttò, S.; Monini, P.; Ensoli, B. Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease. Vaccines 2019, 7, 99. https://doi.org/10.3390/vaccines7030099
Cafaro A, Tripiciano A, Picconi O, Sgadari C, Moretti S, Buttò S, Monini P, Ensoli B. Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease. Vaccines. 2019; 7(3):99. https://doi.org/10.3390/vaccines7030099
Chicago/Turabian StyleCafaro, Aurelio, Antonella Tripiciano, Orietta Picconi, Cecilia Sgadari, Sonia Moretti, Stefano Buttò, Paolo Monini, and Barbara Ensoli. 2019. "Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease" Vaccines 7, no. 3: 99. https://doi.org/10.3390/vaccines7030099
APA StyleCafaro, A., Tripiciano, A., Picconi, O., Sgadari, C., Moretti, S., Buttò, S., Monini, P., & Ensoli, B. (2019). Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease. Vaccines, 7(3), 99. https://doi.org/10.3390/vaccines7030099