Abstract
The HIV-1 reservoir is the major hurdle to a cure. We here evaluate viral and host characteristics associated with reservoir size and long-term dynamics in 1,057 individuals on suppressive antiretroviral therapy for a median of 5.4 years. At the population level, the reservoir decreases with diminishing differences over time, but increases in 26.6% of individuals. Viral blips and low-level viremia are significantly associated with slower reservoir decay. Initiation of ART within the first year of infection, pretreatment viral load, and ethnicity affect reservoir size, but less so long-term dynamics. Viral blips and low-level viremia are thus relevant for reservoir and cure studies.
Highlights
The human immunodeficiency virus type 1 (HIV-1) reservoir is the major hurdle to a cure
To investigate viral and host characteristics that steer HIV1 reservoir size and long-term dynamics in HIV-1 infected individuals who received suppressive combination antiretroviral therapy (ART) for a median duration of 5.4 years, we analyzed longitudinal total HIV-1 DNA levels of 1057 well-characterized individuals enrolled in the Swiss HIV Cohort Study (SHCS) (Fig. 1a)
26.6% of our study population exhibited a positive slope of total HIV-1 DNA levels over a median of 5.4 years of suppressive antiretroviral treatment (ART)
Summary
The HIV-1 reservoir is the major hurdle to a cure. We here evaluate viral and host characteristics associated with reservoir size and long-term dynamics in 1,057 individuals on suppressive antiretroviral therapy for a median of 5.4 years. Viral blips and low-level viremia are significantly associated with slower reservoir decay. Initiation of ART within the first year of infection, pretreatment viral load, and ethnicity affect reservoir size, but less so long-term dynamics. Viral blips and low-level viremia are relevant for reservoir and cure studies. Lifelong ART is required, because effective treatment does not clear the HIV-1 reservoir, which is the major hurdle to cure[3]. More broadly and in accordance with the terminology used the HIV-1 reservoir consists of all HIV-1 infected cells independent of the replication competence of the integrated virus genome[9]
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