Occurrence of Trace-Level Antibiotics in the Msunduzi River: An Investigation into South African Environmental Pollution.

The presence of antibiotics in the environmental matrix has raised concerns regarding their risk to the aquatic ecosystem and human health. Surface water, such as rivers, plays a pivotal role in the dispersion and transport of antibiotic residues. The effective monitoring of these contaminants requires investigating their sources and distribution. While numerous studies have been conducted globally to comprehend the emergence, prevalence, and management of these substances, the investigation of therapeutic antibiotics in Africa remains notably underrepresented. Consequently, data regarding these emerging contaminants in the African aquatic environments are scarce, warranting further exploration. This study aims to investigate the occurrence of four specific therapeutic antibiotics-tetracycline, sulfathiazole, penicillin g, and erythromycin-across different seasons in the Msunduzi River, Eastern South Africa. Three sampling campaigns were conducted during spring, autumn, and winter to assess the presence of these antibiotics in the river. Analyte extraction from water samples was achieved through solid-phase extraction, and quantification was performed using liquid chromatography-mass spectrometry. The findings reveal notable concentrations of these antibiotics in the river at locations closest to a wastewater treatment discharge point. Among the antibiotics studied, tetracycline (158.42-1290.43 ng/L) and sulfathiazole (112.68-1151.25 ng/L) were the most frequently detected compounds across the majority of the sampling sites and tributaries of the river. Erythromycin was less frequently detected in the surface water and wastewater effluent but was found to be a risk to algal species within the river. While wastewater effluents represent a significant source of antibiotic contamination in the river, tributaries from industrial areas and informal settlements were identified as continuous sources of antibiotic pollution. Thus, it is imperative to implement appropriate monitoring protocols to mitigate antibiotic pollution in the aquatic environment.

Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.

BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. OBJECTIVES: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. METHODS: A systematic review and individual patient data meta-analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. STUDY ELIGIBILITY CRITERIA: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. PARTICIPANTS: SOT recipients. INTERVENTION: TMP-SMX prophylaxis versus no prophylaxis. ASSESSMENT OF RISK OF BIAS: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. METHODS OF DATA SYNTHESIS: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100). CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

HIV Pre-Exposure Prophylaxis: New and Upcoming Drugs to Address the HIV Epidemic.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) provides a critical intervention toward ending the HIV epidemic and protecting people with reasons to utilize PrEP. PrEP options continue to expand as new administration modalities offer the potential to tailor PrEP use for individual success. We have provided the evidence for new and emerging antiretroviral agents for PrEP (cabotegravir, lenacapavir, dapivirine, and broadly neutralizing antibodies), divided into pharmacology, animal model, and human data, accompanied by a summary and suggested place in therapy. Cabotegravir is a US Food and Drug Administration (FDA)-approved intramuscular injection given every 2 months with a strong body of evidence demonstrating efficacy for HIV PrEP, lenacapavir administered subcutaneously every 6 months is currently under investigation for HIV PrEP, dapivirine vaginal ring is an available PrEP option for women in certain areas of Africa, and broadly neutralizing monoclonal antibodies have been challenged in demonstrating efficacy in phase 1-2 study for HIV PrEP to date. Clinical literature for individual agents is discussed with data from major studies summarized in tables. This review provides a detailed overview of recently available and premier candidate PrEP drugs.

Pulmonary tuberculosis complicated by pneumothorax, and acute respiratory distress syndrome (ARDS) in the settings of advanced HIV disease: A case report.

Introduction: A large proportion of the global burden of HIV-associated TB occurs in sub-Saharan Africa; including 74% of new cases of TB and 79% of deaths occurs in this area. Spontaneous pneumothorax occurs more frequently in patients with AIDS than the general population with the estimated incidence to be about 2-5% of overall total cases. Tuberculosis ARDS and septic shock are rare but carries extremely poor prognosis. Case summary: A 27 year old male with advanced HIV disease with very low CD4 count presented to Wolaita Sodo University comprehensive specialized hospital, Ethiopia on July 6, 2023. The patient diagnosed with spontaneous pneumothorax secondary to drug susceptible tuberculosis after positive urine LF-LAM and sputum gene expert. He was intubated after emergency tube thoracostomy, and subsequently treated with anti-TB, corticosteroid, broad-spectrum IV antibiotics and high dose cotrimoxazole. The patient developed ARDS due to possible tuberculosis related septic shock and died of multi-organ failure. Discussion: Spontaneous pneumothorax in the setting of HIV raises concern for PCP, though in this case it could be secondary to TB. Tuberculosis related ARDS and septic shock are rare complication but carries poor prognosis especially in setting of AHD. We had limited experience and difficulties in the management of patient with persistent pneumothorax with the concomitant ARDS requiring lung protective management, and this part remain the future area of scientific research. Conclusion: In patients with advanced HIV disease, who present with signs of respiratory failure, the likelihood of spontaneous pneumothorax, TB-ARDS and septic shock should be anticipated in the differential diagnosis and optimal management plan should be designed.

Pharmacogenomic panel testing provides insight and enhances medication management in people with HIV.

OBJECTIVE: Our study aimed to assess the impact of pharmacogenomic panel testing in people with HIV (PWH). DESIGN: Prospective, observational intervention assessment. METHODS: One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants' current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes. RESULTS: Ninety-six participants (median age 53 years, 74% white, 84% men, 89% viral load <50 copies/ml) completed panel testing, yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild-moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in one participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants. CONCLUSION: Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.

Cutibacterium acnes in spine tissue: characteristics and outcomes of non-hardware-associated vertebral osteomyelitis.

Cutibacterium acnes isolation from spine tissue can be challenging because the organism can represent a contaminant. There is a paucity of data regarding the role of C. acnes in non-hardware-associated vertebral osteomyelitis (VO). Herein we evaluate the clinical and microbiological characteristics, treatment, and outcome of patients with C. acnes VO. Data were retrospectively collected from adults with a positive spine culture for C. acnes at Mayo Clinic, Rochester (MN), from 2011 to 2021. Patients with spinal hardware and polymicrobial infections were excluded. Of the subjects, 16 showed radiological and clinical findings of VO: 87.5 % were male, the average age was 58 years (±15 SD), and back pain was the predominant symptom. Of the lesions, 89.5 % involved the thoracic spine. Of the subjects, 69 % had experienced an antecedent event at the site of VO. In five subjects, C. acnes was isolated after 7 d of anaerobic culture incubation. Thirteen subjects were treated with parenteral ß-lactams, and three with oral antimicrobials, without any evidence of recurrence. Twenty-one subjects were not treated for VO, as C. acnes was considered a contaminant; at follow-up, none had evidence of progressive disease. C. acnes should be part of microbiological differential diagnosis in patients with suspected VO, especially in the context of a prior spinal procedure. Anaerobic spine cultures should undergo prolonged incubation to enable recovery of C. acnes. C. acnes VO may be managed with oral or parenteral antimicrobial therapy. Without clinical and radiological evidence of VO, a single positive culture of C. acnes from spine tissue frequently represents contaminants.

Prevention of the Vertical Transmission of HIV; A Recap of the Journey so Far.

In 1989, one in four (25%) infants born to women living with HIV were infected; by the age of 2 years, there was 25% mortality among them due to HIV. These and other pieces of data prompted the development of interventions to offset vertical transmission, including the landmark Pediatric AIDS Clinical Trial Group Study (PACTG 076) in 1994. This study reported a 67.5% reduction in perinatal HIV transmission with prophylactic antenatal, intrapartum, and postnatal zidovudine. Numerous studies since then have provided compelling evidence to further optimize interventions, such that annual transmission rates of 0% are now reported by many health departments in the US and elimination has been validated in several countries around the world. Despite this success, the elimination of HIV's vertical transmission on the global scale remains a work in progress, limited by socioeconomic factors such as the prohibitive cost of antiretrovirals. Here, we review some of the key trials underpinning the development of guidelines in the US as well as globally, and discuss the evidence through a historic lens.

Functional humoral and cellular response of monovalent COVID-19-vaccines against Omicron BA.2 variant of SARS-CoV-2 in patients with chronic lymphocytic leukemia.

We designed a prospective study to evaluate the humoral (using a surrogate virus neutralization test) and cellular (using an IFN-γ ELISpot) immune response among patients with chronic lymphocytic leukemia (CLL) against Wuhan-Hu-1 and Omicron BA.2 strains of SARS-CoV-2, after mRNA-based vaccination. The proportion of patients with a functional humoral response was higher among untreated CLL patients compared to treated CLL patients against both Wuhan-Hu-1 and Omicron BA.2 after the second and the third dose of vaccination, and at 12 months after the first dose. The proportion of positive cellular response against the peptide pool covering the full-length Wuhan-Hu-1 spike protein was similar between untreated and treated CLL patients at all three timepoints. The cellular response to the mutated regions of BA.2 spike protein was lower than the response to the corresponding regions in the ancestral spike after the second dose, but this difference was eliminated after the third dose.

C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial.

OBJECTIVE: COVID-19 severity is correlated with granulocyte macrophage colony-stimulating factor (GM-CSF) and C reactive protein (CRP) levels. In the phase three LIVE-AIR trial, lenzilumab an anti-GM-CSF monoclonal antibody, improved the likelihood of survival without ventilation (SWOV) in COVID-19, with the greatest effect in participants having baseline CRP below a median of 79 mg/L. Herein, the utility of baseline CRP to guide lenzilumab treatment was assessed. DESIGN: A subanalysis of the randomised, blinded, controlled, LIVE-AIR trial in which lenzilumab or placebo was administered on day 0 and participants were followed through Day 28. PARTICIPANTS: Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. INTERVENTIONS: Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. MAIN OUTCOME MEASURES: The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. RESULTS: SWOV was achieved in 152 (90%; 95% CI 85 to 94) lenzilumab and 144 (79%; 72 to 84) placebo-treated participants with baseline CRP <150 mg/L (HR: 2.54; 95% CI 1.46 to 4.41; p=0.0009) but not with CRP ≥150 mg/L (HR: 1.04; 95% CI 0.51 to 2.14; p=0.9058). A statistically significant interaction between CRP and lenzilumab treatment was observed (p=0.044). Grade ≥3 adverse events with lenzilumab were comparable to placebo in both CRP strata. No treatment-emergent serious adverse events were attributed to lenzilumab. CONCLUSION: Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. TRIAL REGISTRATION NUMBER: NCT04351152; ClinicalTrials.gov.

Early switch to oral antibiotic therapy for the treatment of patients with bacterial native vertebral osteomyelitis: a quaternary center experience, systematic review, and meta-analysis.

Recent data suggest that oral therapy can be effective for bone infections. We aim to assess the efficacy of an early switch to oral therapy ( < 2  weeks) compared to a non-early switch in bacterial native vertebral osteomyelitis. We conducted a cohort study at Mayo Clinic, Rochester (MN), between 2019-2021 combined with a systematic review, which queried multiple databases. Data were analyzed using a random-effects model. The cohort study included 139 patients: two received an early switch. Of 3708 citations, 13 studies were included in the final analysis. Meta-analysis demonstrated no difference in treatment failure (odds ratio  =  1.073, 95 % confidence interval 0.370-3.116), but many studies presented high risk of bias. Current evidence is insufficient to conclude the proportion of patients with failure or relapse is different in the two groups. High-quality studies are warranted before early switch can be routinely recommended.

Human Dectin-1 deficiency impairs macrophage-mediated defense against phaeohyphomycosis.

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, ß-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1ß in response to ß-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1ß and TNF-α production, which enhanced fungal killing in an interdependent manner. Deficiency of either Dectin-1 or CARD9 was associated with more severe fungal disease, recapitulating the human observation. Because these data implicated impaired Dectin-1 responses in susceptibility to phaeohyphomycosis, we evaluated 17 additional unrelated patients with severe forms of the infection. We found that 12 out of 17 carried deleterious CLEC7A mutations associated with an altered Dectin-1 extracellular C-terminal domain and impaired Dectin-1-dependent cytokine production. Thus, we show that Dectin-1 and CARD9 promote protective TNF-α- and IL-1ß-mediated macrophage defense against C. cassiicola. More broadly, we demonstrate that human Dectin-1 deficiency may contribute to susceptibility to severe phaeohyphomycosis by certain dematiaceous fungi.

Human-wildlife conflict in the surrounding districts of Alage College, Central Rift Valley of Ethiopia.

The study was conducted between September 2018 and March 2019 to investigate the nature and extent of human-wildlife conflict (HWC) in the surrounding area of Alage College, the Central Rift Valley of Ethiopia, and to assess the perception of the local people to wildlife. For data collection, a total of 140 household (HH) heads were selected randomly for interviews from nine villages using structured and semi-structured questionnaires. Moreover, focus group discussion, key informant interviews, and personal observation were carried out to obtain additional information. Descriptive statistics, Chi-square test (2 tailed), one-way analysis of variance, Pearson correlation coefficient, and Likert scale statements were used to analyze the data. Based on, 66 (47.1%) of the respondents, HH heads, the local people of the area experienced livestock predation leading to HWC. Whereas, (40.7%, n = 57) of the respondents perceived both crop damage and livestock predation as a cause of conflict. A total of 932.43 total livestock unit of livestock and 218 dogs' losses were reported by HH due to predators over the last 5 years. Thus, the largest number of livestock (89.9%) and dogs (100%) attacks was happened due to spotted hyenas. Nearly half of the respondents (49.3%, n = 69) ranked warthogs as the primary crop raiders, while the majority of respondents (82.1%, n = 115) reported maize as a severely damaged cereal crop. More than half, (57.1%, n = 80) of respondents used different methods simultaneously to minimize damage caused by wild animals. About half, (48.6%, n = 68) of respondents had a negative attitude toward wildlife conservation. The level of education and amount of money imposed as a penalty for illegal grazing were affecting the local community's attitudes to wildlife conservation. Using effective methods to reduce damage and loss to crops, including improved livestock husbandry and creating better awareness to the local community could make the locals actor of conservation.

Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial.

BACKGROUND: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. METHODS: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed. FINDINGS: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. INTERPRETATION: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. FUNDING: Humanigen.

Short Communication: A Pilot Study of the Effects of Losartan Versus Placebo on Pneumoproteins in HIV: A Secondary Analysis of a Randomized Double Blind Study.

HIV is an independent risk factor for lung disease, including chronic obstructive pulmonary disease (COPD) and emphysema. Angiotensin receptor blockers may be beneficial in COPD and emphysema through pathways that have been implicated in HIV-related lung disease. We performed a randomized comparison of the effects of losartan versus placebo on the plasma concentrations of the pneumoproteins, surfactant protein D (SPD) and club cell secretory protein (CCSP), in people living with HIV (PLWH). A total of 108 PLWH were included (52 assigned to losartan and 56 assigned to placebo). We found no difference in the change from baseline in log2 concentrations of CCSP or SPD over 1 year of follow-up. For SPD, we found a strong interaction by CD4+ counts, where those with CD4+ counts >350 cells/mm3 treated with losartan had more reduction (improvement) in SPD concentration than those treated with placebo (p value for interaction <.001). In conclusion, we did not find a beneficial effect of losartan on pneumoprotein concentrations in PLWH, but PLWH with higher CD4+ counts may have improvement in SPD when treated with losartan.

Cabotegravir: a novel HIV integrase inhibitor combined with rilpivirine as the first long-acting injectable program for the treatment of HIV infection.

Cabotegravir, a novel HIV integrase inhibitor, shares structural similarity with dolutegravir and bictegravir. Its oral half-life is 32 hours, but cabotegravir nanosuspension for intramuscular injection yields half-lives ranging from 25 to 54 days, enabling extended interval dosing. Drug interactions are minimal, although oral doses require spacing from polyvalent cations, and potent uridine glucuronosyltransferase induction (e.g., rifampin, carbamazepine) requires avoidance due to anticipated subtherapeutic cabotegravir exposure through extended intervals. Randomized clinical trials combined cabotegravir treatment with rilpivirine to demonstrate treatment efficacy in patients living with HIV who had attained virologic suppression, lacked known/suspected mutations to either component, and had not experienced prior HIV treatment failure. Together, oral cabotegravir and rilpivirine maintained viral suppression in the LATTE study while the combination, given intramuscularly, performed comparably to conventional oral therapy in LATTE-2. FLAIR and ATLAS, respectively, demonstrated HIV suppression maintenance for monthly injections in treatment-naive participants and treatment-experienced patients, with ATLAS-2M supporting the efficacy of injections given every 2 months. Investigations to date show an excellent safety profile. Injectable cabotegravir causes short-lived, mild injection site reactions (primarily administration site pain/soreness) that decrease in frequency over time, produce attributable discontinuation rates of at least 2%, and generate satisfaction scores that favor injectable therapy over oral therapy. Virologic failure with resistance development is rare, primarily occurs in the first year of therapy, and is associated with baseline proviral DNA mutations to coadministered rilpivirine. A key component of the first U.S. Food and Drug Administration (FDA)-approved injectable maintenance treatment program for HIV, injectable cabotegravir heralds a new era in HIV treatment innovation. Here we provide a detailed review of the clinical pharmacology, administration and available formulations of the novel HIV integrase inhibitor cabotegravir with in-depth analysis of the clinical trial data, safety, satisfaction and viral resistance development when combined with rilpivirine as the first long-acting injectable program for the treatment of HIV infection.

Hepatotoxicity of contemporary antiretroviral drugs.

PURPOSE OF REVIEW: To 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 FINDINGS: Although 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. SUMMARY: Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.

Hepatotoxicity of Contemporary Antiretroviral Drugs: A Review and Evaluation of Published Clinical Data.

Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs.