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.
We address the problem of learning classifiers for a large number of tasks. We derive a solution that produces resampling weights which match the pool of all examples to the target distribution of any given task. Our work is motivated by the problem of predicting the outcome of a therapy attempt for a patient who carries an HIV virus with a set of observed genetic properties. Such predictions need to be made for hundreds of possible combinations of drugs, some of which use similar biochemical mechanisms. Multi-task learning enables us to make predictions even for drug combinations with few or no training examples and substantially improves the overall prediction accuracy.
Introduction
A major hurdle to HIV-1 eradication is the establishment of a latent viral reservoir early after primary infection. Several factors are known to influence the HIV-1 reservoir size and decay rate on suppressive antiretroviral treatment (ART), but little is known about the role of human genetic variation.
Methods
We measured the reservoir size at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readouts: the reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.
Results
Genome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART.
Conclusions
Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.
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