Background Antiretroviral therapy has transformed HIV infection from a deadly into a chronic condition. Aging people with HIV (PWH) are at higher risk of polypharmacy, potential drug–drug interactions (DDIs), and potentially inappropriate medications (PIMs). This study aims to compare prescribed drugs, polypharmacy, and potential DDIs between young (<65 years old) and elderly (≥65 years old) PWH. The prevalence of PIMs was assessed in elderly. Methods PWH from 2 centers within the Swiss HIV Cohort Study were asked to fill in a form with all their current medications. Polypharmacy was defined as being on ≥5 non-HIV drugs. PIMs were evaluated using Beers criteria. Potential DDIs for the most prescribed therapeutic classes were screened with the Liverpool interaction database. Results Among the 996 PWH included, 122 were ≥65 years old. Polypharmacy was more frequent in the elderly group (44% vs 12%). Medications and potential DDIs differed according to the age group: cardiovascular drugs and related potential DDIs were more common in the elderly group (73% of forms included ≥1 cardiovascular drug; 11% of cardiovascular drugs involved potential DDIs), whereas central nervous system drugs were more prescribed and involved in potential DDIs in younger PWH (26%, 11%). Potential DDIs were mostly managed through dosage adjustments. PIMs were found in 31% of the elderly group. Conclusions Potential DDIs remain common, and PIMs constitute an additional burden for the elderly. It is important that prescribers develop and maintain a proactive approach for the recognition and management of DDIs and other prescribing issues frequently encountered in geriatric medicine.

Background Patients who start combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection show a smaller HIV-1 latent reservoir, less immune activation, and less viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. Patients who started cART <180 days after a documented primary HIV-1 infection and had an HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; noninferiority margin 10%. Results Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group vs 32/32 (100%) in the cART group (difference, 0.00%; 95% confidence interval, –100%, 4.76%). This showed noninferiority of the dolutegravir monotherapy at the prespecified level. Conclusion In this pilot study consisting of patients who initiated cART during primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was noninferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART. Clinical Trials Registration NCT02551523.

Aims The impact of ageing on antiretroviral pharmacokinetics remains uncertain, leading to missing dosing recommendations for elderly people living with human immunodeficiency virus (HIV: PLWH). The objective of this study was to investigate whether ageing leads to clinically relevant pharmacokinetic changes of antiretrovirals that would support a dose adjustment based on the age of the treated PLWH. Methods Plasma concentrations for 10 first‐line antiretrovirals were obtained in PLWH ≥55 years, participating in the Swiss HIV Cohort Study, and used to proof the predictive performance of our physiologically based pharmacokinetic (PBPK) model. The verified PBPK model predicted the continuous effect of ageing on HIV drug pharmacokinetics across adulthood (20–99 years). The impact of ethnicity on age‐related pharmacokinetic changes between whites and other races was statistically analysed. Results Clinically observed concentration–time profiles of all investigated antiretrovirals were generally within the 95% confidence interval of the PBPK simulations, demonstrating the predictive power of the modelling approach used. The predicted decline in drug clearance drove age‐related pharmacokinetic changes of antiretrovirals, resulting in a maximal 70% [95% confidence interval: 40%, 120%] increase in antiretrovirals exposure across adulthood. Peak concentration, time to peak concentration and apparent volume of distribution were predicted to be unaltered by ageing. There was no statistically significant difference of age‐related pharmacokinetic changes between studied ethnicities. Conclusion Dose adjustment for antiretrovirals based on the age of male and female PLWH is a priori not necessary in the absence of severe comorbidities considering the large safety margin of the current first‐line HIV treatments.

Objectives Dolutegravir is widely prescribed owing to its potent antiviral activity, high genetic barrier and good tolerability. The aim of this study was to characterize dolutegravir’s pharmacokinetic profile and variability in a real-life setting and to identify individual factors and co-medications affecting dolutegravir disposition. Methods A population pharmacokinetic model was developed using NONMEM®. Relevant demographic factors, clinical factors and co-medications were tested as potential covariates. Simulations based on the final model served to compare expected dolutegravir concentrations under standard and alternative dosage regimens in the case of drug–drug interactions. Results A total of 620 dolutegravir plasma concentrations were collected from 521 HIV-infected individuals under steady-state conditions. A one-compartment model with first-order absorption and elimination best characterized dolutegravir pharmacokinetics. Typical dolutegravir apparent clearance (CL/F) was 0.93 L/h with 32% between-subject variability, the apparent volume of distribution was 20.2 L and the absorption rate constant was fixed to 2.24 h−1. Older age, higher body weight and current smoking were associated with higher CL/F. Atazanavir co-administration decreased dolutegravir CL/F by 38%, while darunavir modestly increased CL/F by 14%. Rifampicin co-administration showed the largest impact on CL/F. Simulations suggest that average dolutegravir trough concentrations are 63% lower after 50 mg/12h with rifampicin compared with a standard dosage of 50 mg/24h without rifampicin. Average trough concentrations after 100 mg/24h and 100 mg/12h with rifampicin are 92% and 25% lower than the standard dosage without rifampicin, respectively. Conclusions Patients co-treated with dolutegravir and rifampicin might benefit from therapeutic drug monitoring and individualized dosage increase, up to 100 mg/12 h in some cases.

Clinical studies in aging people living with HIV (PLWH) are sparse for the novel integrase inhibitor bictegravir, leading to some uncertainty about dosing recommendations for elderly PLWH. The objective of this study was to investigate the continuous impact of aging on bictegravir pharmacokinetics by combining clinically observed data with modeling to support a safe and efficient anti‐HIV therapy with advanced age. A physiologically‐based pharmacokinetic (PBPK) model was developed for bictegravir with clinically observed data from phase I studies. The predictive model performance was verified using bictegravir plasma concentrations sampled as part of the general therapeutic drug monitoring (TDM) program of the Swiss HIV Cohort Study in young (20–55 years) and elderly PLWH (55–85 years). The verified PBPK model subsequently predicted the continuous impact of aging on bictegravir pharmacokinetics across adulthood (20–99 years). Bictegravir exposure was unchanged in elderly compared with young PLWH when analyzing the TDM data of the Swiss HIV Cohort Study. PBPK simulations predicted clinically observed data from 60 young and 32 elderly PLWH mostly within the 95% confidence interval, demonstrating the predictive power of the used modeling approach. Simulations predicted drug exposure to increase up to 40% during adulthood, which was not statistically significantly different from the age‐related pharmacokinetic changes of other HIV and non‐HIV drugs. Sex had no impact on the age‐related changes of bictegravir pharmacokinetics. Considering the safety margin of bictegravir, a dose adjustment for the novel integrase inhibitor is a priori not necessary in elderly PLWH in the absence of severe comorbidities.