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Sexually transmitted infections and immune activation among HIV-infected but virally suppressed youth on antiretroviral therapy

https://doi.org/10.1016/j.jcv.2018.02.001Get rights and content

Highlights

  • HIV-infected youth have high risk of acquiring sexually transmitted infections (STI).

  • Virally suppressed youth with STIs had lower CD4 + T-cell counts vs those without STIs.

  • Youth with STIs showed evidence of increased markers of immune activation.

Abstract

Background

Human immunodeficiency virus (HIV) infection is associated with chronic immune activation, and concurrent sexually transmitted infections (STIs) may increase immune activation.

Objectives

Because HIV-infected youth are at high risk of STIs and little is known about the impact of STIs on immune activation in HIV-infected youth, we conducted an exploratory study examining the association between STIs and systemic inflammation and immune activation among HIV-infected adolescents.

Study design

Forty-nine behaviorally infected U.S. youth ages 18–24 years with baseline CD4+ T-cells >350 who maintained viral suppression on therapy by week 48 were included. Evaluation for STIs (herpes simplex virus [HSV], Chlamydia trachomatis, syphilis, Neisseria gonorrhoeae) was conducted as standard of care and reported on case report forms. Measures of T-cell subsets, systemic immune activation, and soluble factors were examined at week 48 for differences between participants with an STI diagnosis during the 48 weeks compared to those without an STI.

Results

Forty-three participants (88%) were male; 57% had baseline CD4+ T-cell counts >500 cells/mm3. Eighteen youth were reported to have ≥1 STI. At week 48, participants with STIs demonstrated lower CD4+ T-cell counts (any STI vs. no STI, p = 0.024; HSV vs. no STI, p = 0.022) and evidence of increased systemic immune activation, including higher CD57 intensity, higher HLA-DR intensity, and lower CD28 percentage, when compared to those without STIs. There were no differences in soluble factors between STI groups.

Conclusions

Results indicate novel activation of CD4+ T-cells among HIV-infected youth who have STIs other than HSV, which may contribute to disease progression.

Section snippets

Background

Human immunodeficiency virus (HIV) infection is associated with chronic immune activation leading to loss of T-cells and HIV disease progression [1]. HIV replication in lymph nodes alters node structure, further decreasing CD4+ T-cells [[2], [3], [4]]. Markers of immune activation are associated with declining CD4+ T-cell counts [5], HIV disease progression, [6] and development of persistent inflammation that is not fully reversed by combination antiretroviral therapy (cART) [[7], [8], [9]].

Objectives

Because STIs are common among HIV-infected youth [[11], [21], [22]] and immune activation promotes HIV disease progression, this exploratory study examined the association between STIs and systemic inflammation and immune activation among a sample of HIV-infected adolescents who were virally suppressed on cART.

Study design

Behaviorally HIV-infected 18–24 years-olds with CD4+ T-cell counts >350 cells/mm3 were recruited for the parent study and randomized to early cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir or standard care. Recruitment occurred at 23 U.S. sites of two HIV research networks from 2007 to 2010. Seventy-five youth were randomized to early cART and maintained on the regimen for 48 weeks [9]. These analyses focused on the 49 youth who achieved viral suppression – VL < 100

Results

Characteristics for the 49 youth in this analysis are shown in Table 1.

Differences in T-cells were found between participants with and without STIs (Table 2). Participants with any STI and those with HSV had significantly lower CD4+ T-cell counts at week 48 versus participants without STIs. Participants with HSV (vs. without STIs) had lower CD4+ TemRA T-cell counts. There were no other significant differences in CD4+ or CD8+ T-cell counts or subsets between groups.

MFI and percentage of

Discussion

This is the first study to demonstrate lower CD4+ T-cell counts and increased immune activation in the setting of STIs among virally suppressed HIV-infected youth. Although sex workers with STIs had increases in HIV VL and cytokines [20], our study demonstrated novel markers of immune activation on CD4+ T-cells among youth with STIs other than HSV among a cohort consisting of youth optimally suppressed on cART and with normal CD4+ T-cell counts at entry.

STIs were reported throughout the study,

Competing interests

The authors declare that they have no conflicts of interest.

Funding

This work was supported by The Adolescent Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health [U01 HD 040533 and U01 HD 040474] through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (B. Kapogiannis)], with supplemental funding from the National Institutes on Drug Abuse (K. Davenny) and Mental Health (P. Brouwers, S. Allison). The protocol was co-endorsed by the International Maternal Pediatric Adolescent AIDS Clinical

Ethical approval

This project was approved by the institutional review board at each of the sites involved in the study (listed below).

The following ATN sites participated in this study: University of South Florida, Tampa (Emmanuel, Lujan-Zilberman, Julian), Children’s Hospital of Los Angeles (Belzer, Flores, Tucker), University of Southern California at Los Angeles (Kovacs, Homans, Lozano), Childrens National Medical Center (D’Angelo, Hagler, Trexler), Children’s Hospital of Philadelphia (Douglas, Tanney,

Acknowledgement

The authors thank Bret J. Rudy, M.D. for his critical contributions to this study.

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  • 1

    Present affiliation: U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, United States.

    2

    Present affiliation: Office of AIDS Research, National Institutes of Health, 5601 Fishers Lane, Bethesda, MD, 20892-9310, United States.

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