If a planned path reaches a dead-end, one can simply stop. Or one can turn around, walk back to the last intersection and take another path, or one can consider taking few paths in parallel. The last scenario is reflecti...If a planned path reaches a dead-end, one can simply stop. Or one can turn around, walk back to the last intersection and take another path, or one can consider taking few paths in parallel. The last scenario is reflective of the journey of remdesivir, the first antiviral for the treatment of COVID-19, that was approved by FDA less than 10 months after the isolation of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. As of January 2022, 10 million COVID-19 patients have been treated with remdesivir worldwide, but the journey of this molecule started more than a decade earlier with the search for a cure of hepatitis C virus. The development path of remdesivir before the emergence of COVID-19 represents a valuable example of a preemptive pandemic preparedness, but the pursuit of this path would not have been possible without sustaining support of John C. Martin, whom we will sorely miss for his piercing vision, uncompromising leadership, and genuine compassion for patients suffering around the world.
In the mid 1980's, I flew from Birmingham, Alabama to San Francisco, rented a car, and drove to Palo Alto so that I could meet with John Martin at Syntex. John, along with Julian Verheyden, synthesized ganciclovir, which...In the mid 1980's, I flew from Birmingham, Alabama to San Francisco, rented a car, and drove to Palo Alto so that I could meet with John Martin at Syntex. John, along with Julian Verheyden, synthesized ganciclovir, which had significant in vitro activity against cytomegalovirus (CMV) in vitro. This drug provided my colleagues and me an opportunity to evaluate it as a therapeutic agent for congenital CMV infection, knowing full well that it was mutagenic, teratogenic, and carcinogenic. John in his wisdom convinced the management of Syntex to provide ganciclovir for this disease, allowing me to study this drug in symptomatic congenitally infected children through the NIAID Collaborative Antiviral Study Group (CASG). Certainly, no other person or company would advocate for the use of such a medication in children, regardless of disease severity, because of its toxicity profile. Since these early days, ganciclovir, and subsequently its prodrug valganciclovir, have become the standard of care for the treatment of congenital cytomegalovirus infection. The following commentary defines the need and progress in the development of therapy.
A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (), revolutionized the antiretroviral therapy landscape. Single-...A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (), revolutionized the antiretroviral therapy landscape. Single-tablet regimens provide not only dosing convenience but help optimize adherence and persistence with antiretroviral therapy to achieve durably suppressed viremia with both individual and societal benefits. Given the many excellent options available now, single-tablet regimens are the preferred choice for initiating antiretroviral therapy in almost all patients with rare exceptions for drug interactions and pregnancy, and for simplification of more complex antiretroviral therapy to a single-tablet regimen. In this special commemorative article, we celebrate this astounding advancement in antiretroviral therapy, championed by John C. Martin while CEO of Gilead Sciences, and its transformative impact on HIV care nationally and globally.
BACKGROUND: Gilead Sciences, under Dr. John Martin's leadership, created its Global Access Program to deliver high-quality, affordable medicines to treat and ultimately eliminate some of the world's most challenging-to-t...BACKGROUND: Gilead Sciences, under Dr. John Martin's leadership, created its Global Access Program to deliver high-quality, affordable medicines to treat and ultimately eliminate some of the world's most challenging-to-treat, pervasive, life-limiting diseases not as philanthropy but based on a self-sustaining business model-a highly novel concept in the pharmaceutical realm. John was determined to bring together all key stakeholders from public health officials to doctors and patients around the globe to understand barriers and opportunities in HIV, viral hepatitis, and visceral leishmaniasis (VL) and in so doing, pushed the Gilead team to devise novel strategies to address healthcare disparities in resource-challenged geographies. PURPOSE: This case study provides an overview of the evolution and impact of the Gilead Access to Medicines Program in providing treatments for HIV in low- and lower middle-income countries.
Antivir Ther
· 2022 Apr · PMID 35491570
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The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or m...The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or more small molecule drugs. This review aims to highlight the discovery, development, and impact of one such molecule, namely, emtricitabine (FTC, emtriva), which is one of the most successful drugs in the fight against HIV/AIDS and has been taken by over 94% of individuals infected with HIV in the USA. We also pay tribute to Dr. John C. Martin, former CEO and Chairman of Gilead Sciences, who unexpectedly passed away in 2021. A true visionary, he was instrumental in delivering FTC, as part of combination therapy with TDF (tenofovir, viread) to the global stage. As the fight to eradicate HIV marches on, we honor Dr. Martin's legacy of collaboration, achievement, and hope.
A concept of "all or nothing" inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily...A concept of "all or nothing" inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily single tablet regimen that forever simplified HIV treatment to enhance patient compliance and thus, sustained viral suppression. The making of Atripla incorporated dry granulation and bilayer compression technologies to achieve stability and bioequivalence in an optimal pill size. In 2011, there lacked a standard of care for chronic hepatitis C infections that was safe, simple, short, free of interferon and ribavirin, and with high cure rates. A fixed-dose combination of ledipasvir and sofosbuvir was developed and approved in 2014 to be the first complete daily single tablet regimen for CHC genotype 1 infection. A spray-drying process for particle morphology engineering in a polymer matrix was used for improving bioavailability.
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindi...The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
BACKGROUND: Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure m...BACKGROUND: Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients. PURPOSE: This is a small tribute to John Martin. METHODOLOGY AND CONCLUSION: Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.
BACKGROUND: To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)...BACKGROUND: To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in human immunodeficiency virus (HIV)-infected patients. METHODS: RPV-treated HIV-infected patients from phase 2b or 3 studies rolled-over into this phase 3, open-label study and received RPV 25 mg once daily (QD) with choice of two NRTIs. Adverse events (AEs), plasma viral load, CD4 cell count, and antiviral resistance were evaluated. RESULTS: Of the 482 patients treated, 437 (>90%) patients discontinued study treatment; 371 (77%) had switched to commercially available RPV, 14 (2.9%) discontinued due to AEs, and 6 (1.2%) had virologic failure. In this rollover study, patients were followed up to week 336, although data was limited beyond 288 weeks. Forty-five (9.3%) patients were still undergoing treatment at the time of data cut-off for the current analysis (8 February 2018). The most frequently reported AEs were pregnancy in 7 (1.5%) patients and syphilis in 5 (1.0%) patients. Grade 3-4 AEs were reported in 17 (3.5%) patients, and AEs possibly related to RPV in 23 (4.8%) patients. Over 288 weeks of treatment, 80.1% (95% CI: 74.9%; 84.3%) of patients maintained virologic suppression (HIV-1 RNA <50 copies/mL). The absolute CD4 cell count increased over time until week 192 and remained constant thereafter. CONCLUSIONS: RPV 25 mg QD in combination with an investigator-selected background regimen of two NRTIs demonstrated sustained long-term virologic suppression. The treatment was well-tolerated with no new safety findings.
BACKGROUND: In Nigeria, the effect of Hepatitis B virus (HBV) on long-term liver outcomes in persons with HIV (PLH) has not been described. We determined changes in liver stiffness measure (LSM) using transient elastogra...BACKGROUND: In Nigeria, the effect of Hepatitis B virus (HBV) on long-term liver outcomes in persons with HIV (PLH) has not been described. We determined changes in liver stiffness measure (LSM) using transient elastography over 6 years in HIV mono-infected and HIV-HBV co-infected Nigerians initiating antiretroviral therapy (ART) and factors associated with LSM decline. METHODS: This single centre, cohort study enrolled ART-naïve HIV mono- and HIV-HBV co-infected adults (≥18 years) at the APIN Public Health Initiatives-supported HIV Care and Treatment Centre at Jos University Teaching Hospital, Nigeria, from 7/2011 to 2/2012. LSM at baseline, Years 3 and 6 were analysed using longitudinal models to estimate changes over time and their predictors. RESULTS: Data from 100 (31%) HIV-HBV co-infected and 225 (69%) HIV mono-infected participants were analysed. Median LSM at baseline was 6.10 (IQR: 4.60-7.90) kPa in co-infected and 5.10 (IQR: 4.40-6.10) kPa in mono-infected participants. In adjusted analyses, average LSM was not significantly different between Year 0 and 3 (β = 0.02, -0.22 to 0.26, = 0.87 and Year 0 and 6 (β = -0.02, -0.23 to 0.27, = 0.88) in both groups (>0.05), but co-infected participants had significantly higher LSM than mono-infected throughout follow-up (β = 0.018, 0.019-0.28, < 0.001). Year 3 LSM differed according to ART initiation status by Year 3 (initiators - non-initiators: -0.87, -1.70 to -0.29). CONCLUSION: In this cohort, LSM remained higher among HIV-HBV co-infected versus HIV mono-infected participants throughout follow-up. Our findings emphasize the continuing need for monitoring of liver outcomes in HIV-HBV co-infected populations on ART and the importance of preventing HBV infection among PLH to optimize liver health.
BACKGROUND: Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity. PURPOSE: As HCMV infection affects...BACKGROUND: Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity. PURPOSE: As HCMV infection affects inflammation pathways, especially prostaglandin E2 (PGE2) production via cyclooxygenase 2 enzyme (COX-2), we designed 2'-hydroxychalcone compounds to inhibit human cytomegalovirus. STUDY DESIGN: We first selected the most efficient new synthetic chalcones for their effect against COX-2-catalyzed PGE2. STUDY SAMPLE: Among the selected compounds, we assessed the antiviral efficacy against different HCMV strains, such as the laboratory strain AD169 and clinical strains (naïve or multi-resistant to conventional drugs) and toxicity on human cells. RESULTS: The most efficient and less toxic compound (chalcone 7) was tested against HCMV in combination with other antiviral molecules: artesunate (ART), baicalein (BAI), maribavir (MBV), ganciclovir (GCV), and quercetin (QUER) using Compusyn software. Association of chalcone 7 with MBV and BAI is synergistic, antagonistic with QUER, and additive with GCV and ART. CONCLUSION: These results provide a promising search path for potential bitherapies against HCMV.
BACKGROUND: Few models to predict antiviral response of peginterferon were used in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and the prediction efficacy was unsatisfied. Quantitative antibody to...BACKGROUND: Few models to predict antiviral response of peginterferon were used in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and the prediction efficacy was unsatisfied. Quantitative antibody to hepatitis B core antigen (anti-HBc) is a new predictor of treatment response. We aimed to develop a new model to identify HBeAg-positive Chinese patients who were more likely to respond to peginterferon. METHODS: Data from 140 peginterferon recipients with HBeAg-positive were applied with generalized additive models and multiple logistic regression analysis to develop a baseline scoring system to predict serological response (SR: HBeAg loss and HBeAg seroconversion 24 weeks post-treatment) and combined response (CR: SR plus serum HBV DNA levels <2000 IU/mL 24 weeks post-treatment). RESULTS: Anti-HBc levels, alanine aminotransferase ratio, and HBeAg were retained in the final model. The new model scored from 0 to 3. Among patients with scores of 0, 1, or ≥2, SR was achieved in 6.45% (2/31), 13.21% (7/51), and 55.36% (31/56), respectively, and CR in 3.23% (1/31), 9.43% (5/53), and 25.00% (14/56), respectively. Our model has a higher AUROC for SR comparing to Chan's (Z = 2.77 > 1.96, < 0.05) and Lampertico's (Z = 2.06 > 1.96, < 0.05) model. The negative predictive value for SR and CR were both 100% in patients with score 0 and hepatitis B surface antigen ≥20,000 IU/mL at week 12. CONCLUSIONS: Patients with higher scores at baseline were more likely to respond to peginterferon. This new model may predict the treatment response.
Cidofovir is a broad-spectrum antiviral agent that has shown efficacy against skin lesions caused by human papillomavirus (HPV). We present a case of extensive verruca vulgaris lesions refractory to imiquimod that was re...Cidofovir is a broad-spectrum antiviral agent that has shown efficacy against skin lesions caused by human papillomavirus (HPV). We present a case of extensive verruca vulgaris lesions refractory to imiquimod that was responsive to topical cidofovir therapy, and analyze other case series in the literature of successful treatment of benign HPV-associated skin lesions with topical cidofovir. Topical cidofovir's favorable response rate and tolerability make it a useful treatment option for patients of differing ages and immune status who have nonmalignant HPV-associated skin lesions and desire topical therapy.
BACKGROUND: Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three gal...BACKGROUND: Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms were administered: liquid formulation, tablet form and dispersible scored tablet. METHOD: HIV-infected children <4 years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma concentrations were analysed using nonlinear mixed effects modelling approach. RESULTS: One hundred and fifty children (age: 2.5 years (1.9-3.2), weight 11.1 (9.5-12.5) kg (median (IQR)) were included in this study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36 from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630 lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant effect on 3TC pharmacokinetic. CONCLUSION: This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and dispersible scored tablet) of lamivudine in the target population of young HIV-1-infected children. Galenic form had no significant effect on lamivudine pharmacokinetics.
BACKGROUND: Primary analysis at 24 weeks showed that switching to rilpivirine plus darunavir/cobicistat was non-inferior to continuing a standard three-drug antiretroviral regimen in virologically suppressed people with...BACKGROUND: Primary analysis at 24 weeks showed that switching to rilpivirine plus darunavir/cobicistat was non-inferior to continuing a standard three-drug antiretroviral regimen in virologically suppressed people with HIV. We present efficacy and safety data from the 48-week analysis. METHODS: PROBE 2 is a randomized, open-label trial. Adults who were on a three-drug therapy and had had <50 HIV-1 RNA copies/mL for at least 6 months were randomly assigned (1:1) to 25 mg rilpivirine plus 800/150 darunavir/cobicistat once daily (early switch group) or to continue their regimen for 24 weeks before switching (late switch group). In the 48-week analysis, the efficacy endpoint was the proportion of participants with <50 copies/mL of HIV-RNA (US Food and Drug Administration snapshot algorithm). The trial is registered with ClinicalTrials.gov, number NCT04064632. FINDINGS: 160 participants were recruited and randomized. At week 48, 70 (87.5%) in the early switch group and 76 (94.8%) in the late switch group maintained HIV-RNA <50 copies/mL. Virological failure (≥50 HIV-RNA copies/mL) was not seen in any patient of the early switch group and in 2 subjects in the late switch group none of which had treatment emergent resistance-associated mutation. Adverse events leading to treatment discontinuation occurred in 7 (8.7%) participants in the early switch group and in none in the late switch group. INTERPRETATION: The combination of rilpivirine plus darunavir/cobicistat sustained virological suppression, was associated with a low frequency of virological failure, and had a favorable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and integrase inhibitor-sparing alternative to three-drug regimens.
Gane E, Pastagia M, Schwertschlag U
… +12 more, De Creus A, Schwabe C, Vandenbossche J, Slaets L, Fevery B, Smyej I, Wu LS, Li R, Siddiqui S, Oey A, Musto C, Van Remoortere P
BACKGROUND: This Phase I, two-part, first-in-human study assessed safety/tolerability and pharmacokinetics/pharmacodynamics of single-ascending doses (SAD) and multiple doses (MD) of the oral toll-like receptor-7 agonist...BACKGROUND: This Phase I, two-part, first-in-human study assessed safety/tolerability and pharmacokinetics/pharmacodynamics of single-ascending doses (SAD) and multiple doses (MD) of the oral toll-like receptor-7 agonist, JNJ-64794964 (JNJ-4964) in healthy adults. METHODS: In the SAD phase, participants received JNJ-4964 0.2 ( = 6), 0.6 ( = 6), 1.25 ( = 8) or 1.8 mg ( = 6) or placebo ( = 2/dose cohort) in a fasted state. Food effect was evaluated for the 1.25 mg cohort following ≥6 weeks washout. In the MD phase, participants received JNJ-4964 1.25 mg ( = 6) or placebo ( = 2) weekly (fasted) for 4 weeks. Participants were followed-up for 4 weeks. RESULTS: No serious adverse events (AEs) occurred. 10/34 (SAD) and 5/8 (MD) participants reported mild-to-moderate (≤Grade 2), transient, reversible AEs possibly related to JNJ-4964. Five (SAD) participants had fever/flu-like AEs, coinciding with interferon-α serum levels ≥100 pg/mL and lymphopenia (<1 × 10/L), between 24-48 h after dosing and resolving approximately 96 h after dosing. One participant (MD) had an asymptomatic Grade 1 AE of retinal exudates (cotton wool spots) during follow-up, resolving 6 weeks after observation. JNJ-4964 exhibited dose-proportional pharmacokinetics, with rapid absorption (t 0.5-0.75 h) and distribution, and a long terminal half-life (150-591 h). Overall, no significant differences in JNJ-4964 pharmacokinetic parameters were observed in the fed versus fasted state. JNJ-4964 dose-dependently and transiently induced cytokines with potential anti-HBV activity, including interferon-α, IP-10, IL-1 RA, and/or MCP-1, and interferon-stimulated genes (ISG15, MX1, and OAS1) in serum. CONCLUSIONS: In healthy adults, JNJ-4964 was generally well-tolerated, exhibited dose-proportional pharmacokinetics and induced cytokines/ISGs, with possible anti-HBV activity.
INTRODUCTION: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of D...INTRODUCTION: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of DOR resistance mutations compared with that of resistance mutations for other NNRTIs among HIV-1-infected treatment-experienced and -naïve patients from Poland. METHODS: Resistance to DOR and other NNRTIs was assessed in two datasets: 1760 antiretroviral treatment-naïve HIV-1 patients and 200 treatment-experienced patients. All 1960 sequences were derived from the patients using bulk sequencing. For resistance analyses, Stanford HIV drug resistance database scores were used. RESULTS: Overall, DOR resistance was present in 32 patients (1.62%), of whom 13 (0.74%) were naïve and 19 (9.50%) were treatment-experienced. The most common DOR resistance mutations observed among the naïve patients were A98G and K101E (0.2% each), and those among cART-experienced patients were L100I (2.0%), K101E, V108I, H221Y, and P225H (1.5% each). Furthermore, among the naïve patients, less common resistance to DOR (0.7%) compared with that to nevirapine (NVP) (2.1%; = 0.0013) and rilpivirine (5.40%; < 0.0001) was observed. For sequences obtained from treatment-experienced patients, the frequency of resistance to DOR (9.5%) was lower than that for efavirenz (25.5%; < 0.0001) and NVP (26.0%; < 0.0001). CONCLUSIONS: The frequency of transmitted drug resistance to DOR is low, allowing for effective treatment of antiretroviral treatment-naïve patients and rapid treatment initiation. In cART-experienced patients, this agent remains an attractive NNRTI option with a higher genetic barrier to resistance.
BACKGROUND: Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for HIV-1 infection treatment. Because of its genetic barrier, DOR appears to be a good alternative in switch strategies c...BACKGROUND: Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for HIV-1 infection treatment. Because of its genetic barrier, DOR appears to be a good alternative in switch strategies compared to other NNRTI. Our aim was to evaluate the percentage of people living with HIV (PLWHIV) followed in our center who could be eligible to a DOR-based regimen. METHODS: We collected data from all treatment-experienced PLWHIV, never exposed to DOR and with a demonstrated virological suppression. We analyzed previous genotypic analyses, clinical history, and previous exposure to NNRTIs. RESULTS: We analyzed data from 653 patients, whose characteristics are shown in Table 1. 59% of them presented no resistance mutation (RAM) at genotypic analysis. The most common DOR-related RAM were V106A, Y181V, and Y188L. We also analyzed RAM that can possibly interfere with combination therapy (mostly K65R and M184V). In the end, 81.8% of our patients results to be eligible for a DOR-based therapy regimen. CONCLUSIONS: DOR represents a good option for switch strategies in virological suppressed PLWHIV. It seems to have a higher genetic barrier and a lower risk for resistance mutation development compared to other NNRTI. In our cohort, we found 81.8% of patients who could be eligible for a regimen containing DOR and almost 2/3 of patients who can be treated with the fixed-dose combination DOR/3TC/TDF.
Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication and it is active against both influenza A and B viruses. O...Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication and it is active against both influenza A and B viruses. Oseltamivir is indicated for therapy or post-exposure prevention of influenza A and B. Side effects are uncommon and include mild nausea, gastrointestinal upset, dizziness, and headache. Despite widespread use, oseltamivir has not been associated with clinically apparent liver injury; however, there is growing evidence of possible toxic liver involvement during oseltamivir therapy. To the best of our knowledge, this is the first reported case in Italy linking the development of acute hepatitis and oseltamivir therapy, in a patient suffering from influenza H1N1 infection. We also present a review of the literature on cases of oseltamivir hepatotoxicity, through the consultation of PubMed database, the bibliographical references of various articles and an extensive search using Google. In view of the analyzed results, we suggest that experts should carefully consider the need for inclusion of potential serious liver reactions be added to the oseltamivir product label.