HIV but Not CMV Replication Alters the Blood Cytokine Network during Early HIV Infection in Men - PubMed (original) (raw)

HIV but Not CMV Replication Alters the Blood Cytokine Network during Early HIV Infection in Men

Christophe Vanpouille et al. Viruses. 2022.

Abstract

Objective: CMV coinfection contributes to sustained immune activation in people with chronic HIV. In particular, asymptomatic CMV shedding in semen has been associated with increased local and systemic immune activation, even during suppressive antiretroviral therapy (ART). However, the effect of seminal CMV shedding in people with HIV in the earliest phase of HIV infection is not known.

Methods: Using Luminex, we measured the concentration of 34 cytokines in the blood plasma of sixty-nine men who had sex with men with or without HIV and in subgroups of CMV shedders vs. non-shedders. Differences in blood plasma cytokines between groups were investigated using the multivariate supervised partial least squares discriminant analysis method.

Results: Independently of CMV, we found that concentrations of IP-10, MIG, MCP-1, I-TAC 10, IL-16, and MIP-1β were modulated in the earliest phase of HIV infection compared with control individuals without HIV. In people with HIV, there was no difference in blood cytokines among CMV shedders vs. non-shedders.

Conclusion: In early/acute HIV infection, asymptomatic CMV shedding in semen does not drive additional cytokine changes in blood. Early ART initiation should remain the priority, while the added benefit of CMV suppression during the various stages of HIV infection needs to be further investigated.

Keywords: CMV; HIV; MSM; PLS-DA; blood; cytokine; semen.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

(A) Two-dimensional PLS projections of blood cytokines in people with and without HIV. Shown are PLS-DA projections in two LVs with ellipses representing Hotelling’s 2-samples T2 with 95% confidence intervals in blood plasma for people with early/acute HIV (orange triangles) or without HIV (blue circles). The E-statistic was used to test the statistical differences in the separation between the cytokine profiles of the two groups. The multivariate distance between people with and without HIV was significant (p = 0.02). (B) Effect of early/acute HIV infection on chemokines/cytokines in blood. The statistical significance of 12 cytokines with VIP > 1 identified in the PLS-DA model were tested by Wilcoxon Rank Sum test. Six out of 12 remained significant. Shown is the difference of the log10-transformed concentrations of the 6 chemokine/cytokines in people with or without HIV and plotted as boxplots. For each cytokine and each boxplot, each point represents a participant’s cytokine concentration, the box represents the interquartile range (IQR), the middle line represents the median, while the points beyond the whiskers are outliers.

Figure 2

Figure 2

Two-dimensional PLS projections of blood cytokines in CMV shedders versus non-shedders. Shown are the PLS-DA projections in two LVs with ellipses representing Hotelling’s two-sample T2 with 95% confidence intervals in the blood plasma of people with early/acute HIV who shed CMV (orange triangles) and people who did not shed CMV (blue circles). PLS projections showed a large overlap between the cytokine profiles of CMV shedders versus non-shedders. The separation between the two groups, measured as the energy (E) statistic, was not statistically different (E-statistic p = 0.748).

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