Ryom, L;
Lundgren, JD;
De Wit, S;
Kovari, H;
Reiss, P;
Law, M;
El-Sadr, W;
... D:A:D Study Group, .; + view all
(2016)
Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons.
AIDS
, 30
(11)
pp. 1731-1743.
10.1097/QAD.0000000000001018.
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Abstract
OBJECTIVES: Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. DESIGN: Prospective cohort study. METHODS: Data collection on adverse events of anti-HIV drugs study (D:A:D) participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or α-fetoprotein along with imaging), death, 6 months after last visit or 1 February 2014. Associations between ESLD/HCC and cumulative use of individual antiretrovirals were investigated using Poisson regression adjusting for potential confounders. RESULTS: During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred [incidence 1.01/1000 person-years (95% confidence interval 0.90–1.12)] with a 1-year mortality rate of 62.6%. After adjustment, cumulative (per 5 years) exposure to d4T [relative rate 1.46 (95% confidence interval 1.20–1.77)], ddI [1.32 (1.07–1.63)], tenofovir [TDF, 1.46 (1.11–1.93)] and (fos)amprenavir [APV; 1.47 (1.01–2.15)] was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine [0.51 (0.32–0.83)] and nevirapine [0.76 (0.58–0.98)] were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation. CONCLUSION: Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered among all individuals exposed for longer time periods. The use of d-drugs should furthermore be avoided, where there are alternatives available, and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis-independent, TDF association calls for further investigations.
Type: | Article |
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Title: | Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1097/QAD.0000000000001018 |
Publisher version: | http://dx.doi.org/10.1097/QAD.0000000000001018 |
Language: | English |
Additional information: | Copyright © 2016 Wolters Kluwer Health, Inc. This is the accepted manuscript version of this article published in AIDS; the final published version of record can be found at http://dx.doi.org/10.1097/QAD.0000000000001018 |
Keywords: | (fos)amprenavir, d-drugs, end-stage liver disease, hepatocellular carcinoma, hepatotoxicity, HIV, tenofovir |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health |
URI: | https://discovery.ucl.ac.uk/id/eprint/1476922 |
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