Baseline prevalence and predictors of liver fibrosis among <scp>HIV</scp>‐positive individuals: a substudy of the <scp>INSIGHT</scp> Strategic Timing of AntiRetroviral Treatment (<scp>START</scp>) trial

Matthews, Gail V.; Neuhaus, Jacqueline; Sh, Mehta; Vlahakis, Emanuel; Doroana, Manuela; Naggie, Susanna; Arenas‐Pinto, A; Peters, Lars; Rockstroh, Juergen

doi:10.1111/hiv.12241

Cited by 19 publications

(25 citation statements)

References 35 publications

(45 reference statements)

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“…This was also similar to another study that included Botswana and South African pregnant women, and the baseline CD4 + T cells for Batswana were similar between the HIV/HBV-coinfected and HIV-monoinfected group, whereas that of South Africans were lower in the HIV/HBV-coinfected group [45]. Other studies in South Africa and Tanzania reported marginally lower baseline CD4 + T cells [17, 35].…”

Section: Discussionsupporting

confidence: 86%

Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

Anderson

Gaseitsiwe

Moyo

et al. 2016

Open Forum Infectious Diseases

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Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana.Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques.Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively.Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens.

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Section: Discussionsupporting

confidence: 86%

Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

Anderson

Gaseitsiwe

Moyo

et al. 2016

Open Forum Infectious Diseases

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“…There were relatively few individuals in the study with HBV (2.8%) or HCV (3.7%) infections. However, overall fibrosis‐4 scores were less likely to rise >1.45 in those in the immediate compared to delayed ART groups, an effect that was evident 12 months after randomization and was persistent for 60 months . Thus, underlying liver disease caused by HCV, HBV, alcohol, or another condition is an additional reason to treat all individuals infected with HIV as soon as possible.…”

Section: Hiv Treatmentmentioning

confidence: 99%

Human immunodeficiency virus and liver disease: A comprehensive update

Sherman

Peters

Thomas

2017

Hepatology Communications

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Among persons living with human immunodeficiency virus (HIV) infection, liver disease remains a major cause of morbidity and mortality. While the etiologies are varied and often overlapping in the individual patient, the underlying mechanisms, including oxidative stress, direct activation of stellate cells, HIV interaction with hepatocytes, and bacterial translocation with systemic immune activation, seem to be unifying characteristics. Early and fully suppressive HIV antiretroviral therapy is a mainstay of management either before or concurrent with treatment of etiologic cofactors, including hepatitis C virus, hepatitis B virus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Significant barriers to care that still exist include liver disease recognition, appropriate linkage to care, ongoing substance abuse, and psychiatric comorbidities in the HIV‐infected population. Emerging issues in these patients include acute and chronic hepatitis E, underreported hepatitis D, and a rising incidence of hepatocellular carcinoma. (Hepatology Communications 2017;1:987–1001)

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“…These measures can be used individually or in validated composite scores such as the AST to Platelet Ratio Index (APRI) and Fibrosis‐4 Index (FIB‐4), which have been used as noninvasive markers of liver fibrosis in various populations . In a substudy of 221 START trial participants with transient elastography results, 7.8% had significant liver fibrosis, while higher ALT, higher HIV RNA, and Hispanic/Latino ethnicity were associated with higher elastography scores . In this study, our objective was to use APRI and FIB‐4 to determine the prevalence of and risk factors for liver fibrosis among START study participants at baseline and follow‐up and to assess for an effect of early versus delayed initiation of ART on progression of liver fibrosis over time.…”

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confidence: 99%

Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial

et al. 2019

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The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis‐4 Index (FIB‐4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART‐naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm). The following outcomes were evaluated: fibrosis (APRI > 0.5 or FIB‐4 > 1.45), significant fibrosis (APRI > 1.5 or FIB‐4 > 3.25), hepatic flare, and resolution of elevated APRI and FIB‐4 scores. Of the 4,684 enrolled into the START study, 104 did not have APRI or FIB‐4 results and were excluded. Among 4,580 participants (2,273 immediate treatment; 2,307 deferred treatment), the median age was 36 years, 26.9% were female, and 30.4% were black. Three percent had an alcoholism or substance abuse history, 6.4% had hepatitis B and/or C, and 1.1% had significant fibrosis at baseline. The median CD4 count was 651, and 5.3% had HIV RNA ≤ 200. Immediate arm participants were at lower risk of developing increased fibrosis scores than deferred arm participants (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.57‐0.78; P < 0.001) and more likely to have resolution of elevated baseline scores (HR 1.6; 95% CI 1.3‐1.9; P < 0.001). Conclusions: Significant liver fibrosis was rare among ART‐naïve HIV‐positive persons with high CD4 counts. Our findings suggest a benefit of early ART in preventing the development of liver fibrosis.

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Baseline prevalence and predictors of liver fibrosis among HIV‐positive individuals: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Abstract: At baseline, significant liver fibrosis was observed in approximately 8% of participants, with higher ALT and HIV RNA the only clinical factors associated with increasing TE score. TE will be used annually to monitor fibrosis and evaluate the role of ART in further fibrosis progression.

Cited by 19 publications

References 35 publications

Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

Human immunodeficiency virus and liver disease: A comprehensive update

Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial

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