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      Liver function test abnormalities in a longitudinal cohort of Thai individuals treated since acute HIV infection

      research-article
      1 , , 2 , 3 , 4 , 3 , 4 , 5 , 2 , 6 , 2 , 2 , 3 , 4 , 3 , 4 , 3 , 4 , 3 , 4 , 5 , 2 , 7 , 2 , 3 , 4 , 8 , 2 , on behalf of the SEARCH010/RV254 Study Group , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Journal of the International AIDS Society
      John Wiley and Sons Inc.
      HIV, acute HIV, liver function tests, Acquired Immunodeficiency Syndrome, antiretroviral agents, anti‐HIV agents, Thailand

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          Abstract

          Introduction

          Liver disease is a common cause of non‐AIDS morbidity and mortality in people living with HIV (PLHIV), but the prevalence and significance of liver function test (LFT) abnormalities in early HIV infection is unknown. This study aimed to characterize LFTs in a large cohort of participants with acute HIV infection initiating immediate antiretroviral therapy (ART) and examine the association between LFTs and biomarkers of HIV infection and inflammation.

          Methods

          We measured LFTs at the time of HIV diagnosis and at 4, 12, 24 and 48 weeks after ART initiation in 426 Thai individuals with acute HIV infection from 2009 to 2018. A subset of individuals had data available at 96 and 144 weeks. We excluded individuals with concomitant viral hepatitis. Alanine aminotransferase (ALT) was the primary outcome of interest; values greater than 1.25 times the upper limit of normal were considered elevated. Analyses utilized descriptive statistics, non‐parametric tests and multivariate logistic regression.

          Results

          Sixty‐six of the 426 individuals (15.5%) had abnormal baseline ALT levels; the majority (43/66, 65.5%) had Grade 1 elevations. Elevated baseline ALT correlated with Fiebig stages III to V ( p = 0.001) and baseline HIV RNA >6 log 10 copies/mL ( p = 0.012). Baseline elevations resolved by 48 weeks on ART in 59 of the 66 individuals (89%). ALT elevations at 24 and 48 weeks correlated with Fiebig stages I to II at diagnosis ( p < 0.001), baseline plasma HIV RNA levels <6 log 10 copies/mL ( p < 0.001), abnormal baseline ALT ( p < 0.001), baseline CD4 >350 cells/μL ( p = 0.03) and older age ( p = 0.03). Individuals initiating efavirenz‐based regimens were more likely to have elevated ALT levels at 48 weeks compared with those on non‐efavirenz‐based regimens ( p = 0.003).

          Conclusions

          One in six people with acute HIV infection have elevated LFTs. Clinical outcomes with ART started in acute HIV are generally good, with resolution of ALT elevations within 48 weeks on ART in most cases. These results suggest a multifactorial model for hepatic injury involving a combination of HIV‐associated and ART‐associated processes, which may change over time.

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          Most cited references20

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          Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection.

          The characterization of primary HIV infection by the analysis of serial plasma samples from newly infected persons using multiple standard viral assays. A retrospective study involving two sets of archived samples from HIV-infected plasma donors. (A) 435 samples from 51 donors detected by anti-HIV enzyme immunoassays donated during 1984-1994; (B) 145 specimens from 44 donors detected by p24 antigen screening donated during 1996-1998. Two US plasma products companies. The timepoints of appearance of HIV-1 markers and viral load concentrations during primary HIV infection. The pattern of sequential emergence of viral markers in the 'A' panels was highly consistent, allowing the definition and estimation of the duration of six sequential stages. From the 'B' panels, the viral load at p24 antigen seroconversion was estimated by regression analysis at 10 000 copies/ml (95% CI 2000-93 000) and the HIV replication rate at 0.35 log copies/ml/day, corresponding to a doubling time in the preseroconversion phase of 20.5 h (95% CI 18.2-23.4 h). Consequently, an RNA test with 50 copies/ml sensitivity would detect HIV infection approximately 7 days before a p24 antigen test, and 12 days before a sensitive anti-HIV test. The sequential emergence of assay reactivity allows the classification of primary HIV-1 infection into distinct laboratory stages, which may facilitate the diagnosis of recent infection and stratification of patients enrolled in clinical trials. Quantitative analysis of preseroconversion replication rates of HIV is useful for projecting the yield and predictive value of assays targeting primary HIV infection.
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            Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection

            Background Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy. Methods and Findings We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm3. HIV RNA was 5.5 log10 copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/106 PBMC) vs. Fiebig I (8 copy/106 PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of 0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02). Conclusions Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.
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              Liver disease in the HIV-infected individual.

              Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART era, liver disease is now the most common non-AIDS-related cause of death among HIV-infected patients, accounting for 14%-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                michael.peluso@ucsf.edu
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                17 January 2020
                January 2020
                : 23
                : 1 ( doiID: 10.1002/jia2.v23.1 )
                : e25444
                Affiliations
                [ 1 ] Division of HIV, Infectious Diseases, and Global Medicine University of California San Francisco CA USA
                [ 2 ] SEARCH Thai Red Cross AIDS Research Centre Bangkok Thailand
                [ 3 ] U.S. Military HIV Research Program Walter Reed Army Institute of Research Silver Spring MD USA
                [ 4 ] Henry M. Jackson Foundation for the Advancement of Military Medicine Bethesda MD USA
                [ 5 ] HIV‐NAT Thai Red Cross AIDS Research Centre Bangkok Thailand
                [ 6 ] Armed Forces Research Institute of Medical Sciences Bangkok Thailand
                [ 7 ] Yale University School of Medicine New Haven CT USA
                [ 8 ] The University of Amsterdam Amsterdam The Netherlands
                Author notes
                [*] [* ] Corresponding Author: Michael J Peluso, Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, California, USA. Tel: 415-476-9363. ( michael.peluso@ 123456ucsf.edu )

                Author information
                https://orcid.org/0000-0003-0585-6230
                https://orcid.org/0000-0003-3931-5926
                https://orcid.org/0000-0002-0036-3165
                https://orcid.org/0000-0003-1369-3224
                Article
                JIA225444
                10.1002/jia2.25444
                6968973
                31953919
                64ff7c2d-a4b6-4b7a-9d0a-75b17f1a2c69
                © 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 July 2019
                : 04 December 2019
                Page count
                Figures: 5, Tables: 2, Pages: 9, Words: 6966
                Funding
                Funded by: NIH/NIAID , open-funder-registry 10.13039/100000002;
                Award ID: T32 AI60530‐12
                Funded by: Henry M. Jackson Foundation , open-funder-registry 10.13039/100003896;
                Award ID: W81XWH‐11‐2‐0174
                Funded by: U.S. Department of Defense , open-funder-registry 10.13039/100000005;
                Award ID: W81XWH‐18‐2‐0040
                Funded by:  
                Award ID: R01MH095613
                Award ID: R01NS084911
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:17.01.2020

                Infectious disease & Microbiology
                hiv,acute hiv,liver function tests,acquired immunodeficiency syndrome,antiretroviral agents,anti‐hiv agents,thailand

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