Liver toxicity and risk of discontinuation in <scp>HIV</scp>/hepatitis <scp>C</scp> virus‐coinfected patients receiving an etravirine‐containing antiretroviral regimen: influence of liver fibrosis

Casado, José L.; Mena, Álvaro; Bañón, Sara; Castro, Ángeles; Quereda, Carmen; Moreno, Ana; Pedreira, José; Moreno, Santiago

doi:10.1111/hiv.12274

Cited by 8 publications

(9 citation statements)

References 20 publications

(26 reference statements)

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“…However, in spite of this success, there are still adverse effects incurred from HAART (5) including hepatotoxicity (6), nephrotoxicity (7) and neurotoxicity (8), following large-scale clinical trials on humans as well as animal experimental studies. In addition, there are concerns that the treatment-related drop in morbidity and mortality may actually be overestimated (4) as most studies relies on health-related quality of life outcomes considering only mortality and ignoring treatment-related morbidities.…”

Section: Introductionmentioning

confidence: 99%

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

et al. 2016

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Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

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Section: Introductionmentioning

confidence: 99%

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

et al. 2016

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“…When compared directly with EFV in phase 3 clinical trials, grade 3 or 4 elevations in ALT or AST were less common with RPV: ALT 4% EFV versus 1% RPV; AST 4% EFV versus 2% RPV [14][15][16]. The rate of hepatic adverse drug reactions was not statistically significantly different between ETR and placebo in the phase 3 clinical trials of ETR in antiretroviral treatment-experienced patients (DUET-1 and DUET-2) [17].…”

Section: Nonnucleoside Reverse Transcriptase Inhibitorsmentioning

confidence: 94%

Hepatotoxicity of contemporary antiretroviral drugs

Rivera¹,

Otto²,

Zeuli³

et al. 2021

Current Opinion in HIV and AIDS

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Purpose of reviewTo date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years. Recent findingsAlthough less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents.

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“…A review of the literature clearly shows that first-generation NNRTIs exert significant hepatotoxicity, unlike their second-generation counterparts, which seem to be safe for the liver, even in patients coinfected with hepatitis viruses. It is of note that there are various reports of a lack of association of the presence of advanced LF or cirrhosis with an increased risk of grade 3 or 4 TE in HIV patients exposed to second-generation NNRTIs [ 39 , 40 ]. The lower incidence and severity of hepatic toxicity reported with second-generation NNRTIs is related to the rare occurrence of hypersensitivity reactions and the lower potential for induction of liver enzymes exerted by these drugs.…”

Section: Mechanisms Of Nnrti-induced Liver Injurymentioning

confidence: 99%

“…It is a suitable replacement for patients who are virally suppressed on other NNRTI but have developed toxicities and has become an alternative in HIV/HCV coinfected patients because of its safety and lack of interactions with anti-HCV drugs [ 103 ]. Several studies have shown the safety of ETR regarding liver function [ 52 , 104 ], including in HIV/HCV-coinfected patients with significant LF [ 40 , 105 ]. Regarding metabolic alterations, an initial study with ARV-experienced patients reported no clinically relevant changes over the 24-week study period after initiation of ETR treatment, with grade 3 or 4 changes in lipid, hepatic, and pancreatic laboratory parameters being similar to those in the placebo group [ 106 ].…”

Section: Mechanisms Of Nnrti-induced Liver Injurymentioning

confidence: 99%

NNRTI and Liver Damage: Evidence of Their Association and the Mechanisms Involved

Benedicto

Fuster-Martínez

Tosca

et al. 2021

Cells

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Due to the improved effectiveness and safety of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection has become a manageable, chronic condition rather than a mortal disease. However, HIV patients are at increased risk of experiencing non-AIDS-defining illnesses, with liver-related injury standing out as one of the leading causes of death among these patients. In addition to more HIV-specific processes, such as antiretroviral drug-related toxicity and direct injury to the liver by the virus itself, its pathogenesis is related to conditions that are also common in the general population, such as alcoholic and non-alcoholic fatty liver disease, viral hepatitis, and ageing. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of combined anti-HIV treatment due to their unique antiviral activity, high specificity, and acceptable toxicity. While first-generation NNRTIs (nevirapine and efavirenz) have been related largely to liver toxicity, those belonging to the second generation (etravirine, rilpivirine and doravirine) seem to be generally safe for the liver. Indeed, there is preclinical evidence of rilpivirine being hepatoprotective in different models of liver injury, independently of the presence of HIV. The present study aims to review the mechanisms by which currently available anti-HIV drugs belonging to the NNRTI family may participate in the development of liver disease.

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Liver toxicity and risk of discontinuation in HIV/hepatitis C virus‐coinfected patients receiving an etravirine‐containing antiretroviral regimen: influence of liver fibrosis

Abstract: Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis.

Cited by 8 publications

References 20 publications

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

Hepatotoxicity of contemporary antiretroviral drugs

NNRTI and Liver Damage: Evidence of Their Association and the Mechanisms Involved

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