Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy

Abstract

Historical data regarding time to viral rebound following analytical treatment interruption (ATI) have been used to determine therapeutic efficacy in HIV cure trials; however, such data were collected from studies conducted a decade or more ago and included participants receiving older antiretroviral therapy (ART) regimens with infrequent virologic monitoring. We conducted a study of 22 HIV-infected participants receiving modern ART to determine the kinetics of plasma viral rebound following ATI. Our data suggest that modern ART does not alter kinetics of viral rebound when compared to previous regimens and that immunologic interventions may be necessary to achieve ART-free virologic remission. Clinical Trials Registration ClinicaTrials.gov identifier: NCT03225118.

Keywords: analytical treatment interruption; antiretroviral therapy; human immunodeficiency virus.

Figure 1.

Virologic and immunologic parameters following analytical treatment interruption (ATI) and reinitiation of antiretroviral therapy (ART) in study participants. A, Kinetics of plasma viral rebound following discontinuation of ART. Study participants remained off ART until they met restart criteria. Plasma viremia was determined by Abbott Real-Time HIV-1 Assay with a detection limit of 40 copies of HIV RNA/mL. B, Kaplan-Meier curve of plasma viral suppression (<40 and < 200 copies/mL) during the treatment interruption phase. C, Kaplan-Meier curve of the percentage of study participants (n = 19) remaining off ART during the treatment interruption phase. D, Time required to reach plasma viremia < 40 copies/mL in the study participants following reinitiation of ART. Grey line represents the median value. E, Association between plasma viremia at the end of ATI phase and time to suppress HIV < 40 copies/mL following reinitiation of ART. F, Association between the percentage of CD226⁺TIGIT⁻PD-1⁺CD8⁺ T cells at baseline (prior to ATI) and time to suppress the virus < 40 copies/mL following reinitiation of ART. E and F, Blue circles represent study participants whose plasma viremia reached < 40 copies/mL less than or equal to 4 weeks after reinitiation of ART. Red circles represent study participants whose plasma viremia reached < 40 copies/mL greater than 4 weeks after reinitiation of ART. P value was determined using the Mann-Whitney test. Grey bars indicate median values. Black vertical lines represent 95% confidence intervals.