Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG.Įlvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase.ĭiscrepancies between clinical trials – with low rates of adverse events – and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure. This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. Weight gain was reported with all INSTIs, especially with DTG, with possible differential effects according to sex and ethnicity (female and non-white patients being at increased risk). Neuro-psychiatric (NP) effects are to be monitored with INSTIs, especially with DTG (though reports are at times contradictory) clinicians might want to avoid DTG for patients with history of severe NP symptoms, until clarity is provided. INSTIs are a generally well-tolerated class of antiretrovirals (ARV), and has a higher antiviral potency compared to other classes of ARV.Ĭlinicians and patients need however to be aware of some red flags when starting with and monitoring patients on INSTIs.Īll INSTIs can lead to mild increases in creatinine levels, usually without clinical significance, but caution is needed in patients with low eGFR (<30ml/min), when using other nephrotoxic drugs, such as as tenofovir disoproxil. Safety during pregnancy is also another important issue to further clarify. Pharmacogenetics seems to be a promising tool. Given the importance of cognitive and metabolic co-morbidities in people living with HIV in regard to their quality of life, future research needs to focus on long-term effects of INSTIs in relation to these adverse events. Moreover, due to recent findings on neural tube defects in infants exposed to dolutegravir during their peri-conception period, its use is not recommended for women of childbearing age without proper birth control method, while raltegravir remains the only drug which may be prescribed without caution. Weight gain was reported with all INSTIs, although there are methodological caveats in the analyses and the findings need to be interpreted with caution.
Recent findingsĭolutegravir (DTG) bears the heaviest burden of neuropsychiatric side effects.
The primary focus of this paper is on adults with a brief summary on pregnant women and children/adolescents. We sought answers specifically to issues pertaining to neuropsychiatric adverse events, as well as weight gain, which were the two most important categories of adverse events raised in recent studies based on real-life experience. The goal of this paper is to provide an up-to-date review of adverse events related to the class of integrase strand transfer inhibitors (INSTIs), which became the class of choice in few years.