‘How much raltegravir do you take?’ The answer may not be so obvious: an accidental finding from clinical practice

Abstract

It has been over a decade since the introduction of raltegravir, which has a well-established efficacy and tolerability profile 1, 2. However, until recently, raltegravir has only been available as twice-daily formulations with, as a result, a lower cumulative compliance to therapy and a higher rate of discontinuation compared with the other agents in the class 3, 4. Following encouraging results from the ONCEMRK trial 5, a new raltegravir formulation of 1200 mg once daily was introduced, and has been available in our centre since May 2018. The new once-daily administration appears promising in improving the compliance to raltegravir-containing regimens. However, during our routine clinical activity, we noticed that some of the patients recently switched to raltegravir 1200 mg once daily were incorrectly taking the drug. We then decided to investigate this issue and to determine how widespread it was and proceeded to recall all patients switched to this therapy in our clinical centre between May 2018 and December 2018. We then asked our patients how they were taking raltegravir and collected their opinions on the ease of administration of the new formulation and the onset of side effects. We contacted 98 patients starting raltegravir 1200 mg once daily during the study period: 63 were male (64.3%) and the median age was 55 years [interquartile range (IQR) 49–59 years]. Sixty-nine of them (70.4%) had previously been taking a regimen containing raltegravir 400 mg twice daily. Reasons for switching to the new formulation were: optimization (71 cases; 76.3%), toxicity [13 cases; 14.0%; two cases of gastrointestinal (GI) toxicity, two of renal toxicity, four of central nervous system (CNS) toxicity and five of dyslipidaemia], drug–drug interaction (three cases; 3.2%) and other reasons (six cases; 6.5%). Further details of the patients’ characteristics can be found in Table 1. We noticed that eight (8.2%) patients (six of whom were raltegravir-experienced) misunderstood the physician's indications about the dosage and took just one pill of raltegravir 600 mg per day. However, as a consequence of the short follow-up, no virological failures were recorded among these patients. Only two raltegravir-experienced patients preferred the 400 mg twice-daily formulation, while most patients were satisfied with the new once-daily formulation, with no problems related to the larger dimensions of the pills. Regarding the reports of side effects collected through the questionnaire, eight patients (8%) complained of GI symptoms (nausea or stomach ache): seven of these patients (10%) had previously been on a well-tolerated raltegravir 400 mg twice-daily-based regimen. One patient complained of insomnia, with an evening administration, and one patient naïve for raltegravir complained of headache and dizziness, with a reported regression of symptoms after being switched to raltegravir 400 mg twice daily. Moreover, three patients reported hair loss (of whom two patients had a previous medical history of alopecia). Finally, we recorded seven treatment discontinuations. One patient stopped after two consecutive HIV RNA determinations > 40 HIV-1 RNA copies/mL; the remaining discontinuations were attributable to simplification in four cases (4.1% of the total population) and to GI toxicity in two cases (2.0%). Our data confirm the good tolerability of raltegravir, even with the new once-daily formulation; however, our experience warrants physicians to stress the correct method of administration of the new raltegravir 1200 mg once-daily formulation, in order to avoid errors that may lead to virological failure. AB reports grants from Bristol-Myers Squibb and Gilead Sciences, and nonfinancial support from Bristol-Myers Squibb, ViiV Healthcare and Janssen-Cilag. SDG reports grants from Bristol-Myers Squibb, nonfinancial support from Bristol-Myers Squibb, personal fees from Bristol-Myers Squibb, Gilead Sciences, Abbott, Boehringer Ingelheim, Janssen-Cilag and ViiV and personal fees from GlaxoSmithKline. All other authors report no disclosures. This study was conducted as part of our routine work.