Although international health organizations often focus on the nearly 37 million people worldwide who live with HIV, another sexually transmitted disease—herpes simplex 2 (HSV-2), the main cause of genital herpes, is a far more common condition. According to the World Health Organization, as of 2012, there were 417 million people globally between the ages of 15 and 49 with HSV-2, many of them, like most with HIV, reside in sub-Saharan Africa. And while HSV-2 on its own is not fatal, having the condition makes an individual more likely to contract HIV, just as having HIV raises a person’s risk of HSV-2.
This symbiosis and what it means for a vulnerable population was behind a British team’s effort to document the risk of HIV acquisition in people infected with HSV-2. Scientists at the University of Bristol and Imperial College London delved into multiple studies conducted up to 2017, mostly in Africa, that examined the connection between these 2 chronic infections. They found that individuals with HSV-2 had a decidedly higher risk of acquiring HIV than those without HSV-2. This risk was nearly tripled among the general population and doubled for people in high-risk categories, such as women engaged in sex work, men who frequent sex workers, and men who have sex with men. And when the data was analyzed to separate out individuals who had acquired HSV-2 after the study began versus those who had been infected with it earlier, the team found that the risk of contracting HIV was 5 times greater in the general population.
“The greater cofactor effect for incident HSV-2 infection than for prevalent HSV-2 infection might be because newly acquired HSV-2 infection is associated with an increased frequency and severity of genital ulceration, viral shedding, and inflammation in the genital tract, symptoms and manifestations that decrease with time after infection,” the authors wrote in the discussion section of their report. An HSV-2 infection that is active and symptomatic generates CD4-positive T cells. HIV targets these cells, and genital ulceration and viral shedding can enable HIV to break through the mucosal barrier in the genital area. Once infected with HIV, an individual with HSV-2 is likely to experience increased viral shedding that makes his or her infection more transmissible to others.
Why would HSV-2-positive people who engage in high-risk behavior have double the risk of acquiring HIV while the general HSV-2-positive population’s risk is tripled? The reasons are not entirely clear, the investigators said. “It could be that because the risk of HIV acquisition in higher-risk individuals is already maximized, there is less potential for HSV-2 infection to further increase this risk,” Katharine Looker, PhD, a senior research associate-infectious disease modeler at the University of Bristol and the study’s lead author, told Contagion®. “Alternatively, it could be those higher-risk individuals, once they know they have a HSV-2 infection, take steps to reduce the risk of passing on this infection and to reduce their risk of acquiring other sexually transmitted infections (for example, by using condoms), which lowers their risk of acquiring HIV.”
The study also found that younger individuals with incident HSV-2 have an increased risk of acquiring HIV compared to older individuals with incident HSV-2. “The primary reason for this is that younger adults tend to have higher numbers of sexual partners,” Dr. Looker said. “Since HSV-2 acquisition is also highest in younger adults, and our review showed that new (incident) HSV-2 infection is associated with a higher risk of HIV acquisition compared to existing (prevalent) infection, this could be another contributing factor to higher HIV acquisition rates in young adults.” Dr. Looker added that the evidence that the risk of acquiring HIV due to incident HSV-2 was higher in younger individuals compared to older individuals was based on a limited amount of data, and that the team did not find evidence of any age-associated HIV risk with prevalent HSV-2 infection.
Because HSV-2 is underdiagnosed and antiviral therapies that combat it underutilized, how can clinicians and others in the healthcare community make HSV-2 patients aware of the increased risks of contracting HIV, particularly patients who are newly infected? “While acyclovir and valacyclovir (medications used to treat HSV-2) did not decrease incident HIV-1 in 2 clinical trials, there are still potential indirect public health benefits of being on these medications,” Joshua T. Schiffer, MD, associate member in the Vaccine and Infectious Diseases Division at the Fred Hutchinson Cancer Research Center, associate professor in the Department of Medicine at the University of Washington, and an author of the study, told Contagion®. “For instance, patients receiving careful longitudinal care for their HSV-2 are more likely to benefit from comprehensive education regarding prevention strategies for other sexually transmitted infections. The lack of an effective intervention to decrease HIV incidence by altering HSV-2 disease course is a major barrier. It is possible that certain physicians chose not to highlight the known synergistic risks between HSV-2 and HIV because they do not have an intervention to offer which directly impacts these risks. Prior to licensure of such an intervention, a short-term solution may be a well-organized public-health education campaign targeting healthcare providers whose patients who are at risk of acquiring HIV-1 via sexual contact.”