Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest the article published in Hepatology by Kuniholm et al., which showed that hepatitis E virus (HEV) genotype 3 infection is rare, but has potential to cause chronic HEV infection in human immunodeficiency virus (HIV)‐infected women in the United States.1 In Asian countries, contaminated water supply is the predominant route of HEV infection.2 Nepal is highly endemic for hepatitis E infection, and five epidemics have occurred over the last 30 years.5 All the reported sporadic and epidemic acute hepatitis E infections in Nepal have so far been caused by HEV genotype 1.2 We had this opportunity to study acute hepatitis E among a cohort of HIV‐positive men and women enrolled currently under national antiretroviral program treatment (ART) of Nepal. During the period of January to March 2015, 459 HIV‐infected individuals (274 male, 185 female) visited the ART center as a part of their regular follow‐up. Blood was collected in ethylenediaminetetraacetic acid and subjected for CD4 count within 3 hours. Plasma was separated and samples were used for HIV viral load, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody (anti‐HCV), and HEV antibody immunoglobulin M (anti‐HEV IgM; Wantai Biological Enterprise, Beijing, China) and liver enzyme estimation. Demographic variables along with duration of HIV infection were also recorded. During the same period, sera of 587 healthy blood donors were collected from Kathmandu Valley as a control group and assayed for anti‐HEV IgM. Collection of follow‐up sera and nucleic acid testing for HEV RNA was not performed in the current study. Of 459 HIV‐positive subjects, anti‐HEV IgM was detected in 70 (15.25%) subjects (40 male, 30 female), as compared to (4.42%) of blood donors (P < 0.001; odds ratio [OR]: 3.7 [2.35‐5.92]). HBsAg and anti‐HCV were detected in 24 (5.22%) and 342 (74.50%), respectively. In multivariate analysis, anti‐HEV IgM positivity was associated with CD4+ count >200 cells/µL (P < 0.005; OR, 3.257 [1.36‐7.76]), whereas HCV coinfected subjects were spared (P < 0.001; OR, 0.15 [0.08‐0.27]). We show that in a highly endemic region for HEV, HIV‐infected subjects are more prone to acquire acute HEV infection, as compared to a control population, particularly those with higher CD4+ count and those without HCV coinfection.