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Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing.

ABSTRACT: The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade, but the routes of transmission remain poorly understood. We hypothesized that by pairing single genome sequencing (SGS), to enumerate infecting HCV genomes (viruses), with detailed sexual and drug histories, we could gain insight into the routes of transmission among MSM. We used SGS to analyze blood specimens from eight HIV-infected MSM who had 10 episodes of acute (seronegative) or early HCV infections. Seven of eight men reported condomless receptive anal intercourse (CRAI), six with rectal exposure to semen, and all eight denied rectal trauma or bleeding. Of the 10 HCV infections, eight resulted from transmission of a single virus; one infection resulted from transmission of either one or a few (three or four) closely-related viruses; and one infection resulted from transmission of >10 distinct viruses. The participant infected by >10 viruses reported sharing injection equipment for methamphetamine during sex. Two other participants also injected methamphetamine during sex but they did not share injection equipment and were infected by a single virus. Conclusions: Most HCV infections of HIV-infected MSM without a history of either rectal trauma or bleeding or shared injection equipment were caused by a single virus. Intra-rectal exposure to semen during CRAI is therefore likely sufficient for HCV transmission among MSM. Conversely, rectal trauma or bleeding or shared injection equipment are not necessary for HCV transmission among MSM. These results help clarify routes of HCV transmission among MSM and can therefore help guide the design of much-needed behavioral and other interventions to prevent HCV transmission among MSM.

SUBMITTER: Li H

PROVIDER: S-EPMC7363067 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing.

Li Hui H Marks Kristen M KM Talal Andrew H AH van Seggelen Wouter O WO Akil Bisher B Radix Asa A Huprikar Shirish S Branch Andrea D AD Wang Shuyi S Shaw George M GM Fierer Daniel S DS

PloS one 20200715 7

The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade, but the routes of transmission remain poorly understood. We hypothesized that by pairing single genome sequencing (SGS), to enumerate infecting HCV genomes (viruses), with detailed sexual and drug histories, we could gain insight into the routes of transmission among MSM. We used SGS to analyze blood specimens from eight HIV-infected MSM who had 10 episodes of acute (sero ...[more]

PMID: 32667919

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Project description:BACKGROUND:We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex with men. METHODS:One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100000 per quality-adjusted life-year (QALY) gained. RESULTS:All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor-based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ?1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. CONCLUSIONS:Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence, regular screening with LFTs, with or without an HCV Ab test, is the optimal strategy.

Project description:BACKGROUND:Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. METHODS:We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. RESULTS:Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. CONCLUSIONS:Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.

Project description:The incidence of hepatitis C virus (HCV) infections among human immunodeficiency virus (HIV)-infected men who have sex with men has increased in recent years and is associated with high-risk sexual behavior. Behavioral interventions that target high-risk behavior associated with HCV transmission and treatment with direct-acting antivirals may prevent further HCV infections. We predicted the effect of behavioral and treatment interventions on HCV incidence and prevalence among HIV-infected men who have sex with men up to 2030 using a HCV transmission model parameterized with data from the Swiss HIV Cohort Study. We assessed behavioral interventions associated with further increase, stabilization, and decrease in the size of the population with high-risk behavior. Treatment interventions included increase in treatment uptake and use of direct-acting antivirals. If we assumed that without behavioral interventions high-risk behavior spread further according to the trends observed over the last decade and that the treatment practice did not change, HCV incidence converged to 10.7/100 person-years. All assessed behavioral interventions alone resulted in reduced HCV transmissions. Stabilization of high-risk behavior combined with increased treatment uptake and the use of direct-acting antivirals reduced incidence by 77% (from 2.2 in 2015 to 0.5/100 person-years) and prevalence by 81% (from 4.8% in 2015 to 0.9%) over the next 15 years. Increasing treatment uptake was more effective than increasing treatment efficacy to reduce HCV incidence and prevalence. A decrease in high-risk behavior led to a rapid decline in HCV incidence, independent of treatment interventions.ConclusionTreatment interventions to curb the HCV epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade; reducing high-risk behavior associated with HCV transmission would be the most effective intervention for controlling the HCV epidemic, even if this was not accompanied by an increase in treatment uptake or efficacy. (Hepatology 2016;64:1856-1869).

Dataset Information

Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing.

Publications

Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing.

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