Short communicationSexually transmitted infections and immune activation among HIV-infected but virally suppressed youth on antiretroviral therapy
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.
References (34)
- et al.
Viral and host factors in the pathogenesis of HIV infection
Curr. Opin. Immunol.
(2005) - et al.
Systemic effects of inflammation on health during chronic HIV infection
Immunity
(2013) - et al.
Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group
Lancet
(1997) - et al.
Epstein-Barr virus load and immune activation in human immunodeficiency virus type 1-infected patients
J. Clin. Virol.
(2012) - et al.
Latent and active tuberculosis infection increase immune activation in individuals co-infected with HIV
EBioMedicine
(2015) - et al.
Immune activation in the course of HIV-1 infection: causes, phenotypes and persistence under therapy
HIV Med.
(2016) - et al.
Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection
Clin. Vaccine Immunol.
(2006) - et al.
High soluble CD14 levels at primary HIV-1 infection predict more rapid disease progression
J. Infect. Dis.
(2015) - et al.
Direct relationship between virus load and systemic immune activation in HIV-2 infection
J. Infect. Dis.
(2010) - et al.
Roles of clinical and subclinical reactivated herpes simplex virus type 2 infection and human immunodeficiency virus type 1 (HIV-1)-induced immunosuppression on genital and plasma HIV-1 levels
J. Infect. Dis.
(2008)
Plasma levels of soluble CD27: a simple marker to monitor immune activation during potent antiretroviral therapy in HIV-1-infected subjects
Clin. Exp. Immunol.
Immune reconstitution but persistent activation after 48 weeks of antiretroviral therapy in youth with pre-therapy CD4 > 350 in ATN 061
J. Acquir. Immune Defic. Syndr.
Correlates of sexual activity and sexually transmitted infections among human immunodeficiency virus-infected youth in the LEGACY cohort, United States, 2006
Pediatr. Infect. Dis. J.
New sexually transmitted infections among adolescent girls infected with HIV
Sex. Transm. Infect.
Treatment of cervicitis is associated with decreased cervical shedding of HIV-1
AIDS
The role of coinfections in HIV epidemic trajectory and positive prevention: a systematic review and meta-analysis
AIDS
CD8 T-Cell expansion and inflammation linked to CMV coinfection in ART-treated HIV infection
Clin. Infect. Dis.
Cited by (5)
Alarming high prevalence of non-HIV sexually transmitted infections in a rural population of Southern Uganda
2022, The Lancet Global HealthImmunovirological discordance among female sex workers who start antiretroviral therapy in Burkina Faso
2022, BMC Infectious DiseasesIncidence, Reinfection, and Discrepancy between Sexual Practice and Anatomic Site Positivity of Sexually Transmitted Infections in Youth with HIV
2022, Pediatric Infectious Disease Journal
- 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.