Supplementation with natural compounds, referred to as Natural Health Products (NHPs), is emerging as an applicable strategy in all phases of Alzheimer’s disease (AD) management, alongside pharmacological therapy. Several studies have investigated the potential of NHPs to modulate neurochemical and inflammatory processes associated with clinical decline; however, the results remain inconclusive. To evaluate the influence of NHPs on the clinical outcomes of AD patients, a systematic review was performed by searching the PubMed, Scopus, Cochrane, and Clinical Trials.gov databases for randomized clinical trials (RCTs) exploring the effects associated with NHP supplementation for the treatment of AD. Out of the 34 RCTs analyzed, 50% reported improvements in cognitive function and reductions in neuroinflammatory markers following NHP supplementation, suggesting a potential but inconsistent therapeutic effect. The strongest evidence of benefit in AD patients was found with the use of vitamin D, selenium, and probiotics. A certain incidence of depressive disorders and delirium highlights the necessity to better evaluate the safety and tolerability of B vitamin supplements. Overall, this systematic review found mixed results regarding the use of NHPs in the management of AD. Further evidence is needed to support their use in clinical practice.

Highly active antiretroviral therapy has led to a significant increase in the life expectancy of people living with HIV. The trade-off is that HIV-infected patients often suffer from comorbidities that require additional treatment, increasing the risk of Drug-Drug Interactions (DDIs), the clinical relevance of which has often not been determined during registration trials of the drugs involved. Therefore, it is important to identify potential clinically relevant DDIs in order to establish the most appropriate therapeutic approaches. This review aims to summarize and analyze data from studies published over the last two decades on DDI-related adverse clinical outcomes involving anti-HIV drugs and those used to treat comorbidities. Several studies have examined the pharmacokinetics and tolerability of different drug combinations. Protease inhibitors, followed by nonnucleoside reverse transcriptase inhibitors and integrase inhibitors have been recognized as the main players in DDIs with antivirals used to control co-infection, such as Hepatitis C virus, or with drugs commonly used to treat HIV comorbidities, such as lipid-lowering agents, proton pump inhibitors and anticancer drugs. However, the studies do not seem to be consistent with regard to sample size and follow-up, the drugs involved, or the results obtained. It should be noted that most of the available studies were conducted in healthy volunteers without being replicated in patients. This hampered the assessment of the clinical burden of DDIs and, consequently, the optimal pharmacological management of people living with HIV.

Background/Objectives: People Living with HIV (PLWH) often have comorbidities require polypharmacy, increasing the risk of adverse events (AEs) associated with drug–drug/drug–supplement interactions (DDIs/DSIs). However, DDIs and DSIs, including those involving antiretrovirals (ARVs), and their related effects have not been exhaustively assessed. This study aimed to determine, in HIV patients on HAART who are taking multiple medications, the prevalence of DDIs and DSIs involving both ARVs and non-ARV co-medications, and their clinical relevance and consequences. Methods: In this longitudinal observational study, PLWH receiving HAART were consecutively enrolled at the University Hospital of Salerno and followed up during scheduled visits. Demographic, clinical, and pharmacological data were collected. DDIs/DSIs were identified using Drugs.com, Lexicomp, and the Liverpool HIV Interaction Checker. Interactions classified as major (Drugs.com), consider therapy modification or avoid combination (Lexicomp), and do not coadminister (Liverpool) were deemed highly clinically relevant. This assessment was supplemented with review of SmPCs and the available literature. Results: Among 84 PLWH, 229 interactions were identified, and 37/229 (16.2%) were highly clinically relevant. Eight patients (9.5%) experienced AEs predicted by the tools. Four were DDIs: cobicistat/alprazolam associated with sedation and dyspnoea, rilpivirine/hydroxychloroquine with QT prolongation, bictegravir/ursodeoxycholic acid with rising viremia, and atorvastatin/fenofibrate with myalgia. Four DSIs between bictegravir and supplements containing divalent ions have been associated with increasing viremia. After medication review, alprazolam was replaced with zolpidem, rilpivirine-based HAART with bictegravir/emtricitabine/tenofovir alafenamide, and atorvastatin/fenofibrate with simvastatin/ezetimibe, and ursodeoxycholic acid and supplements were discontinued. These interventions were temporally associated with clinical improvement of interaction-related AEs and good virological control. Conclusions: This study highlights the importance of predicting DDIs/DSIs in PLWH undergoing polypharmacy. Medication review supports clinical decision-making, preventing avoidable adverse outcomes.