Epidemiological risk factors associated with primary infection by Epstein-Barr virus in HIV-1-positive subjects in the Brazilian Amazon region

Abstract

To identify the prevalence and risk factors for primary Epstein-Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51-15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01-2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12-2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79-1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22-3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1-10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.

Figure 1

Frequency of cases and degree of exposure: (A) Frequency of new cases of HAART-free HIV-1 patients coinfected with HIV/EBV in the period between January 2018 and December 2019. (B) Prevalence of cases of HIV/EBV coinfection stratified based on age and sex. (C) Prevalence of EBV genotypes among HIV/EBV coinfected patients. (D) Potential risk/exposure to HIV-1 monoinfection or co-infection. The color gradient was proposed based on data on the frequency of individuals screened according to the intersection of social and sexual factors.

Figure 2

Late initiation of treatment for HIV-1 infection: (A) Frequency for initiation of HIV-1 infection treatment and monitoring, in months, after the primary diagnosis. Patients with multiple infection (HIV/EBV-1/2) initiated treatment later. *p˂0.05. (B) Evaluation of behavioral profiles at different initiation times for HIV-1 infection treatment and monitoring. Condom use after diagnosis was the most frequent behavior at all treatment initiation times.

Figure 3

Symptoms: (A) Frequency of symptomatological categories among the studied groups. (B) STI diversity among individuals with a history of sexually transmitted infections in the studied groups. Blood donors had a poorly diversified history. *** ***: p˂0.001. (C) Diversity of symptoms between the studied groups. Fever and sore throat were the most frequent. (D) Evaluation of the frequency of the symptomatological categories at different initiation times for HIV-1 infection treatment. There was an extreme reduction in the frequency of asymptomatic patients among patients for whom treatment was initiated greater than 12 months after diagnosis.

Figure 4

Epidemiological factors associated with increased viral loads: (A) epidemiological factors associated with increased HIV viral load. (B) Epidemiological factors associated with increased EBV viral load. The x-axis is the odds ratio (OR) values. Horizontal lines represent the 95% confidence interval (CI) for each OR value. Vertical dashed lines delimit an OR equal to 1; therefore, OR values greater than 1 were considered risk factors for increased viral loads. For EBV, when the age of the patients obtained an OR value less than 1, the increase in viral load was inversely proportional to the factor. Symptomatology was a factor dependent on the viral load.