You are here
Aviremia 10-Year Post-ART Discontinuation Initiated at Seroconversion
Sabine I. Kinloch1, Lucy Dorrell2, Hongbing Yang2, Linos Vandekerckhove3, Ward de Spiegelaere3, Eva Malatinkova3, Sabine Yerly4, Daniel Webster5, Margaret Johnson5
1 Infection and Immunity, University College London, London, United Kingdom. 2 University of Oxford, Oxford, United Kingdom. 3 Department of Internal Medicine, Universitair Ziehenhuis Gent, Gent, Belgium. 4 Geneva University Hospital, Geneva, Switzerland. 5 Royal Free London NHS Foundation Trust, London, United Kingdom.
Background: Early ART initiation is associated with impact on HIV-1 reservoir establishment and decay with the potential for virological control post-treatment discontinuation. Underlying mechanisms of post-virological control remain unclear.
Methods: We report on a clade C-infected female patient who has maintained undetectable viremia for 10 years after stopping a 6-year treatment period initiated at PHI with initial virological failure while on ART and describe her virological parameters and HIV-1 specific T cell responses.
Results: A 23-year-old female seroconverted with a 3-week long severe acute retroviral syndrome in October 1997. Baseline characteristics and follow-up viral load (VL) and CD4 T cells data are shown on Figure. Compromised viro-immunological parameters with CD4 <200 cells/mm3 on 3 occasions and VL >750,000 HIV-1 copies(c)/mL (clade C) were present before ART initiation on 20.10.97 (AZT-3TC-indinavir 800 mg tds switched to ritonavir 600 mg bd 2 weeks later). Failure of this regimen up to 94,000 c/mL prompted treatment intensification and aviremia was achieved in April 1999. ART was maintained until January 2004 followed by aviremia for 10 years with preservation of CD4 T cells and CD4/CD8 ratio>1 (Figure). HLA genotype was not one generally associated with a favorable outcome. At 10 years of aviremia (2014), total HIV-1 DNA, integrated HIV-1 DNA and 2-LTR circles were 148.93 (95% CI: 76.99 - 229.64), 134.31 (95% CI: 56.47 – 304.39) and 3.89 (95% CI: 0 - 9.15) HIV-1 copies/million PBMCs, respectively. CD4 and CD8 HIV-1 specific T cell responses showed moderately potent CD8+ T cell inhibition of a clade-matched HIV-1 isolate equivalent to that which we have observed in ART-naïve chronically infected subjects with VL set-point <10,000 HIV-1 copies/mL. Unusually broad gag-specific IFN-γ CD4 responses were detected, of note, targeting multiple regions of genetic vulnerability that are associated with virological control.
Conclusions: Persistence of intermediate levels of total and integrated HIV-1 DNA and broad HIV-1 gag-specific CD4 T cell responses, together with preserved CD8+ T cell viral inhibitory activity were associated with prolonged aviremia post-stopping treatment, suggesting that further insight into CD4 T cells should be gained in terms of the mechanisms underlying virological control post-ART.