Journal Article

Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan

Chien-Yu Cheng, De-Yu Lin, Ning-Chi Wang, Chien-Ching Hung, Pei-Ying Wu, Shih-Ping Lin, Hung-Jen Tang, Chun-Eng Liu, Mao-Song Tsai, Shu-Hsing Cheng, Yi-Chieh Lee, Chia-Jui Yang, Yi-Chien Lee, Hsin-Yun Sun

2017

Overview

Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity. The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

• Publisher: Public Library of Science (PLoS),Public Library of Science
• Subject: Acquired immune deficiency syndrome / Adult / Adverse Events / AIDS / Alanine Transaminase / Alanine Transaminase - blood / Anti-HIV Agents / Anti-HIV Agents - adverse effects / Anti-HIV Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Aspartate Aminotransferases / Aspartate Aminotransferases - blood / Biology and Life Sciences / CD4 antigen / CD4 Lymphocyte Count / Chemical and Drug Induced Liver Injury / Chemical and Drug Induced Liver Injury - enzymology / Chemical and Drug Induced Liver Injury - epidemiology / Chemical and Drug Induced Liver Injury - etiology / Clinical-Trials / Confidence intervals / Disease Management / Division / Drug Eruptions / Drug Eruptions - epidemiology / Drug Eruptions - etiology / Drug resistance / Drug Therapy, Combination / Efavirenz / Exanthema / Female / Hepatitis / Hepatitis B / Hepatitis B surface antigen / Hepatitis B virus / Hepatitis C / Hepatitis C virus / Hepatotoxicity / HIV / HIV Infections / HIV Infections - drug therapy / Hiv-1-Infected Patients / Human immunodeficiency virus / Humans / Incidence / Infected Patients / Inhibitors / Lentivirus / Male / Medicine / Medicine and Health Sciences / Middle Aged / Nevirapine / Nevirapine Use / Nucleosides / Nucleosides - adverse effects / Nucleosides - therapeutic use / Observational studies / Patients / Physical Sciences / Protease Inhibitors / Public health / Q / R / Regression analysis / Research and Analysis Methods / Research Article / Retrospective Studies / Retroviridae / Reverse Transcriptase Inhibitors / Reverse Transcriptase Inhibitors - adverse effects / Reverse Transcriptase Inhibitors - therapeutic use / Ribonucleic acid / Risk Factors / RNA / RNA, Viral / RNA, Viral - blood / Science / Severity of Illness Index / Skin / Statistical analysis / Taiwan / Taiwan - epidemiology / Toxicity / Transmitted Drug-Resistance / Viral Load / Viremia / Viremia - drug therapy / Virus-Infection / Viruses / Womens health / Young Adult