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Open AccessJournal ArticleDOI

Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy.

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TLDR
Improved AHI detection is urgently needed given the difficulty in recruiting subjects early in AHI, and viral sequence diversity proved accurate in estimating time of infection.
Abstract
Background: Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventions. Methods: Cross-sectional screening was employed to detect HIV RNA positive, antibody negative subjects. Date of HIV acquisition was estimated from clinical history and correlated with sequence diversity assessed by single genome amplification (SGA). Twenty-two cytokines/chemokines were measured from enrollment through week 24. Results: Thirty-seven AHI subjects were studied. In 7 participants with limited exposure windows, the median exposure to HIV occurred 14 days before symptom onset. Lack of viral sequence diversification confirmed the short duration of infection. Transmission dates estimated by SGA/sequencing using molecular clock models correlated with transmission dates estimated by symptom onset in individuals infected with single HIV variants (mean of 28 versus 33 days). Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.

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Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection.

TL;DR: In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, it is found that early ART reduced the generation of latently infected cells, reinforcing and extending the concept that new approaches will be needed to eradicate HIV infection.
Journal ArticleDOI

Insights into B cells and HIV-specific B-cell responses in HIV-infected individuals.

TL;DR: B‐cell perturbations in HIV‐infected individuals are discussed, focusing on the skewing of B‐cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues.
References
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Journal ArticleDOI

BEAST: Bayesian evolutionary analysis by sampling trees

TL;DR: BEAST is a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree that provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions.
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Clinical and epidemiologic features of primary HIV infection.

TL;DR: The events leading to the acquisition of HIV and the initial clinical and diagnostic evaluation of 46 patients with primary HIV infection are summarized.
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Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.

TL;DR: It is suggested that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and a role for CTL in protective immunity to HIV- 1 in vivo is indicated.
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Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection.

TL;DR: HIV-1-specific CTL activity is a major component of the host immune response associated with the control of virus replication following primary HIV-1 infection and have important implications for the design of antiviral vaccines.
Journal ArticleDOI

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection

TL;DR: A mathematical model of random viral evolution and phylogenetic tree construction is developed and used to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection, suggesting a finite window of potential vulnerability of HIV- 1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
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