HIV post-treatment controllers (PTCs) are individuals who can maintain low levels of viremia after ART discontinuation. They have primarily been identified from patients treated during acute infection and little is known about PTCs who were treated during chronic infection. Understanding the mechanisms of HIV control in PTCs has implications for the design of novel strategies for HIV remission.
We evaluated 497 participants from 8 ACTG analytic treatment interruption (ATI) studies to identify PTCs who generally maintained viral loads ≤400 HIV RNA copies/mL for ≥24 weeks. Non-PTC control participants were matched by study arm and selected randomly. Total HIV DNA and CA-usRNA were measured in PBMCs at 3 time points: pre-ATI, early and late post-ATI. T cell intracellular cytokine staining (ICS) was performed on PBMCs stimulated with HIV Gag peptide pool and NK cell ICS was performed with PBMCs stimulated with K562 cells. Soluble markers of inflammation were measured with ELISA-based assays.
16 PTCs were identified (3.2% of participants), including 6 treated during early infection (6.6% of this group) and 10 treated during chronic infection (2.5% of this group). Median duration of documented virologic control was 96 weeks. There were no significant differences in pre-ATI CD4+ count, duration of ART, or frequency of protective HLA alleles between PTCs and non-PTCs. Pre-ATI HIV DNA and CA-RNA were detectable in 14% and 29% of PTCs, respectively. HIV DNA and CA-RNA levels did not significantly increase in PTCs after ATI (median DNA and CA-RNA <50 copies/106 PBMCs for all time points). For individuals treated during chronic infection, non-PTCs had higher HIV DNA levels pre-ATI and higher DNA and CA-RNA levels early post-ATI. No significant differences were detected in HIV-specific T or NK cell activity between PTCs and non-PTCs. While there were no significant pre-ATI differences in soluble and T cell markers of inflammation, non-PTCs had increased CD8+ cell activation as well as IP10 and sCD163 levels post-ATI.
While rare, PTCs can be identified from individuals who were not treated during acute HIV infection. PTCs maintained a small HIV reservoir even after ART discontinuation without a significant increase in immune activation or HIV-specific T or NK cell activity. The detection of pre-ATI HIV DNA and CA-RNA did not preclude the possibility of post-treatment control, suggesting inefficient viral replication or antiviral immune activity may mediate this control.