Expert Review of Clinical Pharmacology最新文献

Introduction: For people with type 2 diabetes and/or cardiovascular conditions, deprescribing of glucose-lowering, blood pressure-lowering and/or lipid-lowering medication is recommended when they age, and their health status deteriorates. So far, deprescribing rates of these so-called cardiometabolic medications are low. A review of challenges and interventions addressing these challenges in this population is pertinent.

Areas covered: We first provide an overview of relevant deprescribing recommendations. Next, we review challenges for healthcare providers (HCPs) to deprescribe cardiometabolic medication and provide insight in the patient and caregiver perspective on deprescribing. We summarize findings from research on implementing deprescribing of cardiometabolic medication and reflect on strategies to enhance deprescribing. We have used a combination of methods to search for relevant articles.

Expert opinion: There is a need for rigorous development and evaluation of intervention strategies aimed at proactive deprescribing of cardiometabolic medication. To address challenges at different levels, these should be multifaceted interventions. All stakeholders must become aware of the relevance of deintensifying medication in this population. Education and training for HCPs and patients should support patient-centered communication and shared decision-making. Development of procedures and tools to select eligible patients and conduct targeted medication reviews are important for implementation of deprescribing in routine care.

Objective: This study was conducted to investigate the effects of glucagon-like peptide-1 receptor (GLP-1) agonists on the lipid profiles of patients with type 2 diabetes.

Methods: We retrieved the data of phase 3 randomized controlled trials on GLP-1 agonists in patients with type 2 diabetes from the PubMed, Embase, and Cochrane library up to 11 February 2024. We extracted % changes in low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol/total cholesterol (T-CHO) and triglycerides levels from baseline. Using Bayesian network meta-analysis, mean differences and 95% credible intervals for lipid changes were estimated as a unit of percentage points (%p) by class.

Results: Twenty-six studies covering 22,290 participants were included. The glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonist showed significant differences in LDL-C (range of mean differences: -11.61 to -6.77%p), triglycerides (-19.94 to -13.31%p), and T-CHO (-7.94 to -5.09%p) levels compared to placebo, insulin, and sodium-glucose co-transporter 2 (SGLT2) inhibitors. The GLP-1 agonist significantly reduced T-CHO (-5.20%p; -6.39%p) and LDL-C (-4.32%p; -8.17%p) levels compared to placebo and SGLT2 inhibitors, respectively.

Conclusions: The GIP/GLP-1 dual agonist positively affects the lipid profiles of patients with type 2 diabetes. This may contribute to a lower risk of cardiovascular disease in patients with type 2 diabetes.

Protocol registration: PROSPERO (CRD42021282668).

Introduction: Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering.

Areas covered: This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data.

Expert opinion: During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.

Introduction: Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance.

Areas covered: The authors reviewed clinical trials and cohort studies providing evidence of benefits and risks of current antiretroviral (ARV) drugs as switching options for PLWH in various scenarios. The literature search included clinical trials, meta-analyses, observational studies, and review articles in English published after 2000, and current HIV treatment guidelines in English and Spanish as of February 2024.

Expert opinion: New ARV drugs offer advantages in efficacy and safety over previous options but may also have adverse effects. Second-generation integrase inhibitors and tenofovir alafenamide show benefits as switching options in various scenarios, though more research is needed on potential weight gain and metabolic issues. Injectable long-acting ART is promising for switching strategies, but finding the optimal combination of new drugs remains challenging.

Introduction: The treatment of HIV infection has been revolutionized in recent years thanks to the advent of dual antiretroviral regimens, administered orally or as long-acting injectable formulations. Here, we provide an update on the usefulness of therapeutic drug monitoring (TDM) of antiretroviral drugs to optimize the management of people with HIV (PWH) in the current scenario.

Areas covered: A MEDLINE PubMed search for articles published between January 2014 and January 2024 was completed matching the terms HIV, antiretrovirals and TDM. Moreover, additional studies were identified from the reference list of retrieved articles.

Expert opinion: Available antiretroviral treatments achieve a response rate of 90%-95%, making the routine TDM of antiretroviral drugs of limited clinical value. However, there are still some important applications of TDM in selected clinical conditions, such as assessing patient compliance or suspected drug-drug interactions (DDIs). Indeed, we are increasingly having to deal with polypharmacy and DDIs in the context of an aging patient with comorbidities that may potentially alter the pharmacokinetics of antiretroviral drugs. Finally, the role of pharmacogenetics, which is closely related to TDM, in influencing both the disposition of antiretrovirals and the course of DDIs should also be considered.

Introduction: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH).

Areas covered: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management.

Expert opinion: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.

Background: This study examined the plasma concentration, clinical efficacy, and safety of dolutegravir (DTG) in Chinese people with HIV (PWH).

Methods: In this observational study, HIV-positive individuals on DTG-based regimens for at least 6 months were included. Plasma DTG concentrations were measured 1 month after initiating treatment. Viral loads (VL) and CD4+ T cell counts were evaluated at baseline and after 1 and 6 months of therapy. High-performance liquid chromatography was used for measuring DTG concentrations, polymerase chain reaction for VL, and flow cytometry for CD4+ T cell counts. Safety assessments included monitoring liver enzymes, serum creatinine estimated glomerular filtration rate, and adverse reactions.

Results: Eighty-two Chinese PWH were enrolled. Average VL decreased significantly from baseline by 3.1 log at 1 month and 3.5 log at 6 months. CD4+ T cell counts increased from 273 cells/mm³ at baseline to 378 cells/mm³ and 446 cells/mm³ after 1 and 6 months, respectively. Seventy-five percent achieved undetectable VLs (<20 copies/mL) by 6 months. C_max and C_τ were 4.63 and 1.98 μg/mL, respectively. The safety profile was favorable with only 4.88% experiencing transient dizziness.

Conclusion: Preliminary findings suggest higher DTG plasma concentrations in Chinese PWH compared to Western populations, with promising short-term efficacy and safety.

Introduction: People with HIV are living longer due to advances in antiretroviral therapy. With improved life expectancy comes an increased lifetime risk of comorbid conditions - such as cardiovascular disease and cancer - and polypharmacy. Older adults, particularly those living with HIV, are more vulnerable to drug interactions and adverse effects, resulting in negative health outcomes.

Area covered: Antiretrovirals are involved in many potential drug interactions with medications used to treat common comorbidities and geriatric conditions in an aging population of people with HIV. We review the mechanisms and management of significant drug-drug interactions involving antiretroviral medications and non-antiretroviral medications commonly used among older people living with HIV. The management of these interactions may require dose adjustments, medication switches to alternatives, enhanced monitoring, and considerations of patient- and disease-specific factors.

Expert opinion: Clinicians managing comorbid conditions among older people with HIV must be particularly vigilant to side effect profiles, drug-drug interactions, pill burden, and cost when optimizing treatment. To support healthier aging among people living with HIV, there is a growing need for antiretroviral stewardship, multidisciplinary care models, and advances that promote insight into the correlations between an individual, their conditions, and their medications.