Severe lactic acidosis during tenofovir disoproxil fumarate and cobicistat combination for HIV patient.

Lactic acidosis is a rare but serious side effect in individuals receiving nucleoside reverse transcriptase inhibitors. An underweight woman with HIV was admitted to our hospital because of nausea and diffuse myalgia. Her antiretroviral regimen had been changed to tenofovir disoproxil fumarate (TDF)/emtricitabine and darunavir/cobicistat 3 months prior, after which her renal function had gradually declined. After admission, she was diagnosed with lactic acidosis, and a liver biopsy suggested mitochondrial damage. Her plasma tenofovir levels were elevated at the onset of lactic acidosis. We hypothesise that the patient's low body weight, combined with the addition of cobicistat, induced renal dysfunction and led to elevated plasma tenofovir concentrations, resulting in mitochondrial damage and lactic acidosis. Careful monitoring of renal function and lactic acidosis is required during use of TDF-containing regimens for underweight HIV patients, particularly when combined with cobicistat.

Acute Ischemia of Lower Extremities Caused by Ergotamine Toxicity due to Pharmacologic Interaction With Cobicistat in an HIV-Positive Patient.

Ergotism is an uncommon condition that affects patients with exposure to ergot alkaloids causing ischemia of extremities. We report the case of lower extremities ischemia caused by ergot toxicity in a human immunodeficiency virus (HIV) positive individual due to the interaction between ergot alkaloid and Cobicistat. In addition, we present a brief review of medical, and pharmacological aspects of this condition. To our knowledge, this is the second reported case describing this interaction.

Prescribing intranasal steroids in HIV-positive patients: systematic review of the literature.

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve patients with HIV-1: subgroup analyses of the phase 3 AMBER study.

Background: The once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is approved for the treatment of HIV-1 infection. The 48-week efficacy and safety of D/C/F/TAF versus darunavir/cobicistat + emtricitabine/tenofovir disoproxil fumarate (control) in treatment-naïve adults were demonstrated in the phase 3 AMBER study. Objective: To describe AMBER outcomes across patient subgroups based on demographic and clinical characteristics at baseline. Methods: AMBER patients had viral load (VL) ≥1000 copies/mL, CD4+ cell count >50 cells/µL, and genotypic susceptibility to darunavir, emtricitabine, and tenofovir. Primary endpoint was the proportion of patients with virologic response (VL <50 copies/mL; FDA snapshot). Safety was assessed by adverse events, estimated glomerular filtration rate (cystatin C; eGFRcystC), and bone mineral density. Outcomes were assessed by age (≤/>50 years), gender, race (black/non-black), baseline VL (≤/>100,000 copies/mL), baseline CD4+ cell count (50 years and women, relative to their comparator groups, regardless of treatment arm (notably, sample sizes were small for patients >50 years and women). Improvements in eGFRcystC and stable bone mineral density were observed with D/C/F/TAF overall, and results were generally consistent across subgroups. Conclusions: For treatment-naïve patients in AMBER, initiating therapy with the D/C/F/TAF single-tablet regimen was an effective and well-tolerated option, regardless of demographic or clinical characteristics.

HIV treatment simplification to elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) plus darunavir: a pharmacokinetic study.

BACKGROUND: As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) with darunavir. METHODS: A single arm, open-label 48-week study was conducted of regimen simplification to E/C/F/TDF plus darunavir 800 mg daily from stable therapy including two nucleoside/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor. Participants had plasma HIV viral load consistently < 200 copies/mL for ≥ 6 months, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, and no genotypic resistance to major components of the study regimen. Plasma viral load was measured at weeks 2 and 4, then every 4 weeks throughout the study. Safety laboratory assessments were conducted at baseline and at weeks 12, 24, 36, and 48. Antiretroviral drug concentrations were measured at baseline and once ≥ 2 weeks after the regimen change. RESULTS: Ten HIV-infected adults (8 male and 2 female; median age 50.5 years) were enrolled. All maintained virologic suppression on the new regimen for 48 weeks. One subject experienced a decrease in eGFR from 62 mL/min at baseline to 52 mL/min at week 12; study medications were continued and his eGFR remained stable (50-59 mL/min) thereafter. No subjects discontinued study medications for renal function changes or other adverse events. Darunavir trough concentration were lower on the new regimen than on darunavir/ritonavir 800/100 mg (n = 5; p < 0.05). CONCLUSIONS: Despite low darunavir trough concentrations, treatment simplification to a two-pill, once-daily regimen of E/C/F/TDF plus darunavir was safe and effective for 48 weeks among 10 selected treatment-experienced HIV-infected patients. Trial registration The study protocol was registered with ClinicalTrials.gov (NCT02199613) on July 22, 2014.

Renal effects of novel antiretroviral drugs.

Chronic kidney disease (CKD) is a critical comorbidity for patients living with HIV, with an estimated prevalence between 2.4 and 17%. Such patients are increasingly affected by diseases associated with ageing, including cardiovascular disease and CKD, and the prevalence of risk factors such as smoking and dyslipidaemia is increased in this population. Proteinuria is also now recognized as a common finding in individuals living with HIV. While combination antiretroviral (ARV) treatments reduce CKD in the HIV-infected population overall, some ARV drugs have been shown to be nephrotoxic and associated with worsening renal function. Over the last few years, several highly efficacious new ARV agents have been introduced. This brief review will look at the novel agents dolutegravir, raltegravir, elvitegravir, cobicistat, tenofovir alafenamide fumarate and atazanavir, all of which have been licensed relatively recently, and describe issues relevant to renal function, creatinine handling and potential nephrotoxicity. Given the prevalence of CKD, the wide range of possible interactions between HIV, ARV therapy, CKD and its treatments, nephrologists need to be aware of these newer agents and their possible effect on kidneys.