Treatment in Seroconversion Maintains HIV-Specific Immune Responses Similar to Long-Term Slow Progressors

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

1. 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.
2. Kinloch-de Loes S et al. HIV-1 specific T cells during prolonged antiretroviral treatment in HIV-1 seroconverters. 17th Annual BHIVA Conference, 6-8 April 2011, Bournemouth. Abstract 029.

Links to external websites are current at time of posting but not maintained.