Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated... Show moreAntiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut -resident bacteria that produce short-chain fatty acids (SCFAs)-crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk. Show less
Mac Donald-Ottevanger, M.S.; Prins, M.; Dissel, J. van; Rier, N.; Reimerink, J.; Zijlmans, W.C.W.R.; ... ; Boyd, A. 2022
Background Hepatitis A virus (HAV) and hepatitis E virus (HEV) have enteric modes of transmission and are common causes of acute hepatitis in low- and middle-income countries. HEV is also... Show moreBackground Hepatitis A virus (HAV) and hepatitis E virus (HEV) have enteric modes of transmission and are common causes of acute hepatitis in low- and middle-income countries. HEV is also characterised as a zoonotic infection and is prevalent in high-income countries. Data on HAV and HEV prevalence in Suriname, a middle-income country in South America, are scarce. Methods Serum samples of 944 and 949 randomly selected patients attending the Emergency Department at the Academic Hospital of Paramaribo, the capital of Suriname, were analysed for anti-HAV antibodies (anti-HAV) and anti-HEV antibodies (anti-HEV), respectively. Determinants of anti-HAV and anti-HEV positive serology were evaluated using multivariable logistic regression. Results Anti-HAV prevalence was 58.3% (95% CI 55.4 to 61.4%) and higher prevalence was independently associated with belonging to the Tribal or Indigenous population and older age. Anti-HEV prevalence was 3.7% (95% CI 2.6 to 5.0%) and higher prevalence was associated with Tribal and Creole ethnicity and older age. Conclusions In Suriname, exposure to HAV is consistent with a very low endemic country and exposure to HEV was rare. Both viruses were more prevalent in specific ethnic groups. As anti-HAVantibodies were less frequently found in younger individuals, they could be susceptible to potential HAV outbreaks and might require HAV vaccination. Show less
Background In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide... Show moreBackground In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015.Methods In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years.Findings Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5.2 per 1000 person-years [95% CI 5.0-5.5]). The highest incidence was observed in men who have sex with men (MSM; 7.7 per 1000 person-years [7.3-8.2]) and was lower in people who inject drugs (PWID; 1.7 per 1000 person-years [0.7-4.1]) and other key populations (1.0 per 1000 person-years [0.8-1.2]). In MSM, incidence increased in 2007 to 14.3 per 1000 person-years and fluctuated between 8.7 and 13.0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6.1 cases per 1000 person-years and remained steady between 4.1 and 4.9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26.9 per 1000 person-years [95% CI 23.9-30.3]). The highest incidence rate was observed in MSM (38.5 per 1000 person-years [33.9-43.7]) and was lower in PWID (10.9 per 1000 person-years [3.5-33.8]) and other key populations (8.9 per 1000 person-years [6.3-12.5]). In MSM, reinfection incidence fluctuated between 38.0 and 88.9 per 1000 person-years from 2006 to 2015, reaching 55.6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41.4 per 1000 person-years, followed by further decreases to 24.4 per 1000 person-years in 2017 and 11.4 per 1000 person-years in 2019.Interpretation The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Show less
Deelen, J.; Kettunen, J.; Fischer, K.; Spek, A. van der; Trompet, S.; Kastenmuller, G.; ... ; Slagboom, P.E. 2019
