Insights from systematic reviews (2019–2024) and drug interaction database analysis in people with HIV and comorbidities

Abstract

Background

This study investigates drug-drug interactions (DDIs) in people with HIV (PWH) receiving antiretroviral therapy (ART) with comorbidities. We focus on pharmacological factors and evaluate DDI notifications from online databases, emphasizing the clinical relevance of pharmacokinetic, pharmacodynamic, and pharmacogenomic variations.

Methods

A comprehensive literature search was conducted using PubMed, ScienceDirect, Google Scholar, and the Cochrane Library for studies published between January 2019 and September 2024. Newly identified DDI evidence was analyzed by comparing DrugBank, Drugs.com, and the Liverpool HIV databases.

Results

Eleven studies met the inclusion criteria. The findings of these studies showed the critical importance of considering DDIs in PWH with tuberculosis (TB), malaria, and pulmonary hypertension. Severe adverse drug reactions associated with ARTs, including efavirenz, darunavir, nevirapine, and atazanavir-ritonavir, especially when combined with treatments for TB and malaria. Key interactions included reduced drug levels from rifampicin and QT prolongation from artemether-lumefantrine. Pharmacogenomic factors, such as CYP2B6 slow metabolism during pregnancy, influenced outcomes. Database discrepancies were noted, especially for riociguat interactions and ritonavir through inhibition of P-gp or OATP1B1 functions.

Conclusions

DDIs in PWH receiving ART with comorbidities have highlighted the crucial need for personalized treatment. Incorporating pharmacokinetic, pharmacodynamic, and pharmacogenomic factors is essential for optimizing therapy outcomes.