Lessons from acute HIV infection

Abstract

Purpose of review: Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption).

Recent findings: The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection. Robust HIV-specific CD8 T-cell responses lower viral set points. Phylogenetic analyses of founder viruses demonstrated unique bottleneck selections and specific genetic signatures to optimize for high-fitness variants and successful transmission events. HIV clades, route of transmission and the presence of minor variants may affect vaccine protection. Antiretroviral treatment in AHI results in smaller HIV reservoir size, better CD4 T-cell recovery and fewer virus escapes.

Summary: The knowledge of untreated and treated AHI informs the development of vaccines, in that preventive vaccines will require broad coverage for multiple clades and antigenic variants associated with unique bottleneck selections. Vaccines that help the host to control viremia could minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission should be studied in early-treated individuals who have few or no viral escape mutants and a more preserved immune system.

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FIGURE 1

Longitudinal viral load values (log₁₀ copies/ml) are plotted vs. the number of days from the first reactive RNA (day 0) for n = 50 acute cases (33 from Africa and 17 from Thailand) with two or more enzyme immunoassay (EIA) nonreactive/nucleic acid testing (NAT)-reactive samples. Regression splines (in black) with participant-specific slopes and intercepts were fit using the first year of viral load data for each region (Africa and Thailand). Reproduced with permission from [^▪▪].