Drug-drug interactions can be either pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions are the primary concern with ARV drugs. Pharmacokinetic interactions occur when one drug alters the absorption, distribution, metabolism or excretion of another drug, possibly increasing or decreasing its plasma concentration. For ARV drugs the interaction types of concern are absorption, metabolism and excretion. …
In general, watch out for the potent enzyme inducers such as rifampicin, rifabutin, phenytoin and carbamazepine Specific interactions by ARV drug class to be aware of and their management, where appropriate, include: INSTIs Dolutegravir with metformin: adjust metformin dose. All INSTIs with cationic chelation (e.g. iron, magnesium, calcium, zinc), including antacids containing these cations: separate …
Christina C. Chang1, Martyn A. French2 Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne VIC UWA Medical School and School of Biomedical Sciences, The University of Western Australia, Perth WA Last reviewed: July 2019
The advent of antiretroviral therapy (ART) revolutionised the care of patients with human immunodeficiency virus (HIV) infection. However, from the late 1980s, when zidovudine monotherapy was introduced, through to the late 1990s, when combination ART became standard of care, clinicians began to recognise that some patients experienced an exacerbation of a previously treated opportunistic infection or …
An IRIS is best described in relation to the type of provoking pathogen e.g. tuberculosis-associated IRIS (TB-IRIS) or cryptococcosis-associated IRIS (C-IRIS) because the immunopathogenesis may differ for different types of pathogen. Further classification is based on the body locality or organ involved, e.g. cryptococcal meningitis IRIS (CM-IRIS), or MAC-IRIS lymphadenitis. The temporal relationship between recognition …
There are no accepted diagnostic tests for an IRIS. Diagnosis of an IRIS is therefore made clinically on the basis of the temporal relationship between starting ART and disease onset, disease manifestations including exclusion of alternative diagnoses, a fall in plasma HIV viral load (indicating that ART is effective) and direct or indirect evidence of …
An IRIS is an undesirable outcome of restoring immune responses against an active (sometimes unrecognised) HIV-related infection or antigens of non-viable pathogens remaining after treatment of the infection (7). The strongest risk factors for an IRIS are a low CD4+ T cell count (usually <50/mL) and a high pathogen load (3, 7, 13) The latter is a …
An IRIS mostly occurs between 2 weeks and 3 months after ART commencement or ART intensification but may occur earlier (within days) and as late as a year after treatment. Temporal onset of an IRIS is particularly difficult to attribute in patients with erratic ART adherence. Typically, IRIS patients had a very low CD4+ T cell count …
For patients with a suspected paradoxical IRIS, the initial consideration is exclusion of a recurrence of the associated infection or development of a new infection. For example, when suspecting paradoxical TB-IRIS, considerations should include non-adherence to TB medications, infection with drug-resistant mycobacteria, new community-acquired pneumonia, PJP and viral infections. Investigations should include sputum microscopy and …
Given that severe CD4+ T cell deficiency when ART is commenced is a risk factor for an IRIS, prevention of CD4+ T cell depletion through early diagnosis and treatment of HIV infection regardless of CD4+ T cell count, as supported by the findings of the START study (33), is the most effective measure for reducing the risk …