Treatment in seroconversion maintains HIV specific immune responses similar to long term slow progressors
1 August 2011. Related: Conference reports, Treatment strategies, Basic science and immunology, BHIVA 17th Bournmouth 2011.
Charlotte Walker, HIV i-Base
Recent studies by Hocqueloux et al suggest that long-term control of viraemia is possible after discontinuation of prolonged ART initiated at seroconversion. [1] This study compared a cohort of 15 long-term non-progressors (LTNPs) with spontaneously controlled viraemia with a cohort of 20 long-term treated HIV-1 seroconverters (LTTS), all of whom started ART at the time of seroconversion resulting in ART-induced controlled viraemia. [2]
LTNPs were defined as having an absence of clinical progression with no CD4 T cell and without using treatment. They have controlled viraemia (are elite controllers) and low viral reservoirs.
Immunovirological parameters defined for this study included:
- The size of viral reservoirs and residual replication (cell associated HIV-1 DNA and RNA respectively)
- Cellular immunity (HIV-1 specific CD4 and CD8 T cells)
- The role of HIV-1 specific CD8+ T cells in viraemic control
- Polyfunctionality associated with virological control
- Slow improvement of HIV-1 specific CD8 T cell function in LTTS
- HIV-1 specific CD8 T-cells in LTNPs are functional in relation to cytokine production, proliferation and cytotoxic capacity
Inclusion criteria of the two study groups included:
- LTNPs: =>7 years with <1000 HIV-1 copies/mL, CD4 >500 cells/mm3 in absence of ART, clinically healthy and with no history of OIs
- LTTS: HIV-1-positive on ART since seroconversion, ART =>4 years and long-term viral suppression (<50 copies/mL)
Study participants were matched in terms of gender, age, ethnicity, transmission route, CD4 count, viral load and cell-associated DNA and RNA. The only significant difference (p=0.06) was between CD4/CD8 T-cell ratios.
Results of the study suggest comparable levels of highly polyfunctional HIV-1 specific CD4+ and CD8+ T cells in both LTTS and LTNPs. Polyfunctional T-cell profiles and low viraemia in the presence/absence of ART were seen in both groups. There was a trend towards a higher magnitude and breadth of HIV-1 specific CD8+ T cells in LTNPs compared to LTTS which is thought to have been driven by a response against the GAG proteins.
The study concluded that prolonged ART initiated at the point of HIV seroconversion is associated with immuno-virological features which resemble those of HIV-1 LTNPs.
References
- Hicqueloux L et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS. 2010 Jun 19;24(10):1598-601.
- Kinloch-de Loes S et al. HIV-1 specific T cells during prolonged antiretroviral treatment in HIV-1 seroconverters. 17th Annual BHIVA Conference, 68 April 2011, Bournemouth. Abstract 029.