Antiretroviral Therapy Initiation Leads to Short-Term Spike in Viral Shedding Among Patients with HIV/HSV-2 Coinfection

Patients with HIV and herpes simplex virus coinfection see an increase in herpes viral shedding when they begin antiretroviral therapy, according to new research; although, the effect appears to be short-lived.

Previous research has shown that antiretroviral therapy can have an adverse impact on people with chronic herpes virus infection. Investigators from the University of Washington, Baylor All Saints Medical Center, the Fred Hutchinson Cancer Research Center, in Seattle, Washington, and the Simmons Transplant Institute, in Dallas, Texas, wanted to gain a better understanding of how and when that worsening of herpes infection occurs, and whether it is sustained long-term.

To study the question, the investigators tracked 45 patients who were HIV positive and also infected with HSV-2, some of whom were on antiretroviral therapy, some of whom were not. The majority—38 patients—were men. Those patients conducted daily genital swabs and also tracked their symptoms. They had follow-up visits with the investigators over up to 3, non-contiguous 60-day periods.

A total of 6425 genital swabs were taken. In patients not taking antiretroviral therapy, shedding was detected on 19.4% of days. For patients taking antiretroviral therapy, however, it was a different story. During the first 90 days after initiation of antiretroviral therapy, genital herpes viral shedding was present 30.2% of days; however, after 90 days on antiretroviral therapy, these patients experienced genital herpes simplex virus shedding on 23.3% of days. The investigators found that patients on antiretroviral therapy saw herpes viral shedding drop at an annual rate of 23%, or about 2% per month.

“This provides additional support to previous clinical observations of herpetic genital ulcers as a manifestation of HIV-related immune reconstitution inflammatory syndrome and suggests that the mechanism of reactivation is loss of immune control and increased epithelial viral replication,” wrote lead author Emily S. Ford, MD, of the University of Washington, and colleagues.

Dr. Ford and colleagues noted that no lesions were reported on 80% of the days, patients tested positive for viral shedding, suggesting that the risk of transmitting HSV-2 to sexual partners is likely higher in the days and weeks initially after initiating antiretroviral therapy.

Exactly why patients lose control of herpes virus reactivation during immune reconstitution is not clear. Dr. Ford and colleagues said the question deserves more study.

From a clinician standpoint, the authors say this research could lead to changes in the treatment of patients with HIV and HSV-2 coinfection.

“Current guidelines recommend anti-herpes simplex virus therapy as determined by symptoms, with consideration of chronic suppressive therapy at antiretroviral therapy initiation for those with CD4+ cell count <250 cells/mL,” they noted.

They said treatment with acyclovir did not appear to reduce the risk of herpes virus transmission among patients with HIV infection taking antiretroviral therapy. However, acyclovir did reduce rates of genital ulcer disease in patients with herpes simplex virus and HIV.

Over the long term, however, Dr. Ford and colleagues said antiretroviral therapy seems to help.

"[O]ne important idea in the paper is that immediately post-antiretroviral therapy, and further out post-antiretroviral therapy are very different scenarios in the course of co-infection," Dr. Ford said in an interview with Contagion®. "Trying to understand the changes that the immune system undergoes immediately post-antiretroviral therapy is an important and very interesting current challenge."

The study, “Increase in herpes simplex virus shedding at initiation of antiretroviral therapy (ART) and decrease in shedding over time on ART in HIV and HSV-2 infected persons,” was published in the journal AIDS.