A Lower Viral Set Point but Little Immunological Impact After Early Treatment During Primary HIV Infection

Abstract

The Primo-SHM trial, a multicenter randomized trial comparing no treatment with 24 or 60 weeks of combination antiretroviral therapy (cART) during primary human immunodeficiency virus (HIV) infection (PHI), recently demonstrated that temporary early cART lowered the viral set point and deferred the need for re-initiation of cART during chronic HIV infection. This study examined whether the beneficial effect of early treatment was caused by preservation of immunological responses. Twenty-seven treated and 20 untreated PHI individuals participating in the Primo-SHM trial were compared at viral set point, that is, 36 weeks after baseline or after treatment interruption, respectively, for a diverse set of immunological parameters. The results show no differences between treated and untreated individuals at the level of effector T-cell formation or replication capacity of the T-cells; regulation of various T, B, natural killer, or dendritic cells; polyfunctionality of the CD8 T-cells; preservation of CD4 T-cells in the gut associated lymphoid tissue; or immune activation. There were subtle differences in the quality of the cytolytic CD4 T-cell response: 11% (median) of CD4 T-cells of the early treated individuals produced the cytolytic molecule perforin compared to 5% in untreated individuals (p=0.046), and treatment caused a modest increase in CD4 T-cells expressing both perforin and granzyme B (median 9% vs. 4% of CD4 T-cells; p=0.045). Early treatment had a modest positive effect on the quality of the CD4 T-cell response. It remains unclear, however, whether these subtle immunological differences were the cause or a result of the lower viral set point in patients who received early treatment.