Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study

Abstract

Background: Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost.

Methods: We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States.

Findings: We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences.

Interpretation: GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH.

Funding: The Center for Disease Control and Prevention.

Keywords: Burden of disease; Economic modeling; Genital herpes; Genital ulcer disease; HSV-1; HSV-2; Herpes simplex virus; Neonatal herpes; Probability tree; Quality-adjusted life years; Sexually transmitted disease.

Fig. 1

Probability trees for people with genital HSV-1 (Panel a) and genital HSV-2 (Panel b), and modelled complications following infrequent or frequent recurrences of HSV-1 and HSV-2 outbreaks (Panel c). People with symptomatic primary infection with genital HSV-1 (Panel a) and HSV-2 (Panel b) could experience mild to moderate complications or severe complications in the primary infection period. People with recurrences could also experience mild to moderate complications in the recurrent period (Panel c), regardless of their symptom status during the primary infection period. Severe complications beyond the primary infection stage were possible for i) those with genital HSV-1 upon reaching age 60 years and ii) those with HSV-2 who experienced severe complications in the primary stage. Assumptions regarding the probability, duration, and quality of life impact of complications were based on data regarding urinary retention due to sacral radiculitis (for mild to moderate complications during primary infection and recurrences), data regarding aseptic meningitis (for severe complications during primary infection), and data regarding Mollaret's meningitis (for severe complications beyond primary infection for those with HSV-2).

Fig. 2

Probability tree for neonatal HSV infection. The number of QALYs lost due to neonatal HSV is calculated independently from the main HSV-1 and HSV-2 trees. Postpartum infection is generally transmitted through oral contact with caregivers; thus, we do not consider this route of infection in our study.

Fig. 3

Average number of QALYs lost per GH infection acquired in 2018 among people aged 18–49 years in the U.S. population, by age group, sex, and HSV type. Error bars represent one standard deviation uncertainty below and above point estimates, which were approximated as one-fourth of the 95% uncertainty ranges. The precise results are reported in the Supplement (Suppl. Table S2).

Fig. 4

Breakdowns of QALYs lost per GH infection acquired in 2018 for people aged 18–49 years in the U.S. population. The upper graphs show the percentage QALYs lost per genital HIV-1 infection that can be attributed to recurrent outbreaks (‘Recur’), psychosocial impacts (‘Psycho’), and ‘all other’ (including the primary outbreak, mild to moderate complications, and severe complications). The lower graphs show the percentage QALYs lost per HSV-2 infection that can be attributed to the psychosocial impacts (‘Psycho’), infrequent recurrent outbreaks (‘Infreq’), frequent recurrent outbreak with episodic treatment (‘Freq (episodic T)’), and ‘all other’ (including the primary outbreak, frequent recurrent outbreak on CST, mild to moderate complications, and severe complications).

Fig. 5

The total lifetime number of QALYs lost due to genital HSV infections acquired in 2018 among people aged 18–49 years in the U.S. population, by sex and HSV type. Error bars represent one standard deviation uncertainty below and above point estimates, which were approximated as one-fourth of the 95% uncertainty ranges. The precise results are reported in the Supplement (Suppl. Table S3).

Fig. 6

Average number of QALYs lost per neonatal HSV infection acquired in 2018 in the US population (left panel) and total number of QALYs lost due to neonatal HSV acquired in 2018 in the US population (right panel). The simulation length represents the length of time considered in the analysis after the first year of neonatal disease onset. Lifetime QALYs lost were used in the main analysis. Error bars represent one standard deviation uncertainty below and above point estimates, which were approximated as one-fourth of the 95% uncertainty ranges. The precise results are reported in the Supplement (Suppl. Table S4).

Fig. 7

One-way sensitivity analyses on key parameters. The vertical dark red dashed lines represent base case outcomes. Panel (a) and panel (b) display the lifetime QALYs lost per genital HSV-1 and HSV-2 infection in the US among people aged 18–49 years, respectively. Panel (c) shows the total QALYs lost associated with genital HSV-1 in the US among people aged 18–49 years, and panel (d) shows the total QALYs lost associated with HSV-2 infections in the US among people aged 18–49 years. In the base case scenario, drawing on a prior study by Fisman, we modelled the psychosocial disutility following diagnosis as a 1% reduction initially. We assumed a one-time reduction in disutility after the year of diagnosis and the disutility remains constant thereafter and decreases to zero on the year the person stops experiencing symptomatic GH recurrences. We assigned the proportion of HSV-1 infections that were genital as 20%, the utility loss from a symptomatic outbreak as 0.15, and the discount rate as 0.03 per year. The utility estimate for a symptomatic outbreak was based on Fisman's study on a small sample of patients (n = 39) from a genital herpes support group; these patients may over-report their utility loss associated with an outbreak. Therefore, we also considered the utility loss estimate from the GBD study, which is a non-STI-specific utility estimate for a symptomatic outbreak. The GBD symptomatic outbreak disutilities were 0.05 per primary symptomatic outbreak and 0.006 per recurrent symptomatic outbreak.