The immune response against Tat protein protects against HIV/AIDS progression.
The HIV-1 Tat protein is a regulatory protein produced early after viral infection that plays a key role in virus replication and expression, cell-to-cell viral transmission and HIV/AIDS progression. CNAIDS has thus undertaken studies to evaluate the effects of the host immune response against Tat. The results of these observational studies indicate that only a minority of HIV+ patients develops an anti-Tat immune response and that in these individuals disease progression is very slow. In particular, the presence of an anti-Tat humoral (antibody) response is associated to an asymptomatic state and clinical stability of the disease. Tat represents therefore an optimal target for the development of a vaccine against HIV that could counteract the progression towards AIDS.
CNAIDS conducted 4 observational studies in Italy and South Africa for a total of 738 HIV+ volunteers with the aim of collecting data on the frequency, intensity, quality and persistence of the anti-Tat immune response in both asymptomatic and antiretroviral (cART)-treated HIV+ subjects. The results of these studies indicate that anti-Tat antibodies, for reasons still to be determined, are detected only in a minority (15-25%) of HIV+ individuals, and that their presence is associated with a slower progression towards AIDS and a more effective response to therapy.
Further analyses of the following observational studies are ongoing to clarify the role of anti-Tat immunity and to identify other prognostic markers useful to the clinical and therapeutic management of HIV/AIDS:
- Longitudinal observational study to evaluate the impact of anti-Tat immunity in the progression of HIV infection under cART (ISS OBS T-002). This study was conducted in Italy on 128 cART-treated, virologically suppressed (i.e. with virus not measurable in blood) HIV+ adults, followed for 3 years
- Longitudinal observational study to evaluate the impact of anti-Tat immunity on the progression of HIV infection in asymptomatic, naïve-to-therapy HIV+ adults (ISS OBS T-003). This study was conducted in Italy on 61 participants that were monitored for 3 years
- Cross-sectional observational study aimed at evaluating the prevalence of anti-Tat antibodies in South African naïve-to-therapy or cART-treated HIV+ adults (ISS OBS T-004). The study was conducted on 531 volunteers (265 naive and 266 cART-treated) at the MEDUNSA Clinical Research Unit (MeCRU), in Gauteng, and the Walter Sisulu University HIV Vaccine Research Unit in Mthatha, Eastern Cape, South Africa
- Finally, a new longitudinal observational study is ongoing to identify the effects of the Tat protein and anti-Tat immune responses (induced by infection or Tat vaccination) in the formation and maintenance of HIV-1 reservoirs in the peripheral blood of cART-treated HIV-infected participants (ISS OBS T-005). The study is conducted in collaboration with the Istituti Fisioterapici Ospitalieri (IFO) - S. Gallicano Hospital, Rome, and foresees the enrolment of about 100 volunteers