Management of the Drug-Drug Interactions Between Valproic Acid and Dolutegravir-A Case Study.

OBJECTIVE: Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia. CASE REPORT: A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium. CONCLUSIONS: We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

No effects of nirmatrelvir/ritonavir on darunavir plasma trough concentrations: a case report.

COVID-19 may be associated with worst outcomes in people living with HIV compared with HIV-negative patients. Nirmatrelvir/ritonavir can be safely co-administered with all the HIV antiretroviral drugs, without considering dose adjustment. However, no studies have formally investigated the effect of a double booster (ritonavir plus cobicistat) regimen on darunavir concentrations. We presented a case describing the lack of effects of adding nirmatrelvir/ritonavir on darunavir plasma trough concentrations in a patient with HIV already on treatment with a booster-based antiretroviral regimen. We believe this could be a reassuring message for physicians, allowing them to prevent unnecessary denial of COVID-19 treatment or inappropriate discontinuation of co-medications in patients with HIV.

The Role of Staphylococcus aureus in Mastitis : A Multidisciplinary Working Group Experience.

BACKGROUND: Breastfeeding women are at risk of developing mastitis during the lactation period. Staphylococcus aureus has emerged as the community-acquired pathogen responsible for virulence (methicillin resistance and Panton-Valentine leukocidin toxin producing). RESEARCH AIM: The aim was to compare the microorganisms responsible for mastitis and breast abscesses during breastfeeding. METHODS: This observational study was conducted with a sample of women (N = 60) admitted to our hospital between 2016 and 2018. Participants affected by mastitis and breast abscess were studied and cared for by a multidisciplinary working group. A diagnostic breast ultrasound identified the pathology. RESULTS: Twenty-six participants (43.3%) were affected by mastitis and 34 (56.7%) by breast abscess. The most common microorganism identified was Staphylococcus aureus (S. aureus; mastitis, n = 13; abscesses, n = 24). Methicillin resistance was identified in 21 (44.7%) S. aureus strains: 17 (80.9%) cases of abscess and four (19.1%) cases of mastitis. The median number of months of breastfeeding was smaller in the methicillin-resistant S. aureus (MRSA) cases (median = 3, range = 1-20 months) than in the methicillin-sensitive S. aureus (MSSA) cases (median = 6.5, range = 3-21 months). The Panton-Valentine leukocidin toxin gene was detected in 12 (25.5%) cases (MRSA, n = 8, 66.7%; MSSA, n = 4, 33.3%). Hospitalization was required more frequently in MRSA (n = 8, 38%; five Panton-Valentine leukocidin positive) than in MSSA cases (n = 5, 19%; one Panton-Valentine leukocidin positive). Four women out of the eight MRSA cases (50%) that were Panton-Valentine leukocidin positive stopped breastfeeding during mammary pathologies, three (37.5%) participants continued breastfeeding until the follow-up recall, and one case was lost at follow-up. CONCLUSION: Clinical severity was probably complicated by the presence of the Panton-Valentine leukocidin toxin, which required hospitalization more frequently.