Immune Activation and Inflammation Among HIV-infected Youth with STIs

Results indicate novel activation of CD4+ T-cells among HIV-infected youth who have STIs aside from HSV, contributing to disease progression.

Tanya Kowalczyk Mullins, MD, MS

Patients with HIV infection experience chronic immune activation as a result of disease progression, which is associated with declining CD4+ T-cell counts and development of persistent inflammation. Despite the many benefits of combined antiretroviral therapy (cART), these alterations in immune function cannot be fully reversed. Sexually transmitted infections (STIs), which are common among young patients with HIV, are also linked to systemic effects such as immune activation and inflammation.

Tanya Kowalczyk Mullins, MD, MS, pediatrician and clinical researcher, Cincinnati Children’s Hospital who specializes in the prevention of HIV and other STIs in adolescents, set out with colleagues to study the association between STIs and systemic inflammation and immune activation, among a sample of HIV-infected virally suppressed cART adolescents.

Patients included in the study were 18—24 years old, had been behaviorally infected with HIV, and presented with CD4+ T-cell counts > 350 cells/mm3. Seventy-five patients were recruited at 23 US sites, and patients then received early cART for 48 weeks.

Of the 75 patients recruited, 49 achieved viral suppression by week 24 and maintained suppression through week 48. Patients were monitored for STIs, specifically herpes simplex virus (HSV), syphilis, chlamydia and gonorrhea, at pre-entry, baseline and periodically throughout the study period. Patients also underwent numerous laboratory studies to characterize immune activation and markers of inflammation.

Results of the study revealed that patients who were diagnosed with any STI during the study had significantly lower CD4+ T-cell counts at the conclusion of the study period compared with those patients who did not contract an STI. In addition, patients who were diagnosed with STIs other than HSV demonstrated novel markers of immune activation on CD4+ T-cells.

Mullins and colleagues found that patients contracted STIs throughout the study period, indicating ongoing risky sexual behavior despite counseling by health care providers. They suggest that “because STIs in HIV-infected youth are associated with HIV transmission and systemic inflammation, developing safer sex interventions specifically targeting HIV-infected youth is critical.”

HIV-infected youth in the study with STIs also had lower CD4+ CD28+ percentage.

“Because lower CD28 levels are associated with terminal differentiation and disease progression, these findings further support that STIs may contribute to chronic immune activation among HIV-infected youth even when viral replication is controlled," Mullins and colleagues observed.

Study authors noted a number of limitations: the timing of STI diagnosis was unknown, meaning researchers could not establish causality; a small number of participants limited the power of the study; the site of STIs was not reported, meaning differences in immune activation by site could not be determined.

Overall, Mullins and colleagues concluded that despite these limitations, clinical evidence of inflammation and immune activation were clear, the study findings were biologically plausible, and they suggest further studies are needed.

This study, “Sexually transmitted infections and immune activation among HIV-infected but virally suppressed youth on antiretroviral therapy,” was published in the May 2018 issue of the Journal of Clinical Virology.

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