Age-Related Changes in Plasma Concentrations of the HIV Protease Inhibitor Lopinavir

Abstract

The advent of highly active antiretroviral therapy in the treatment of HIV disease has substantially extended the lifespan of individuals infected with HIV resulting in a growing population of older HIV-infected individuals. The efficacy and safety of antiretroviral agents in the population are important concerns. There have been relatively few studies assessing antiretroviral pharmacokinetics in older patients. Thirty-seven subjects aged 18-30 years and 40 subjects aged 45-79 years, naive to antiretroviral therapy, received lopinavir=ritonavir (400=100) bid, emtricitibine 200 mg qd, and stavudine 40 mg bid. Trough lopinavir concentrations were available for 44 subjects, collected at 24, 36, and 96 weeks. At week 24, older age was associated with higher lopinavir trough concentrations, and a trend was observed toward older age being associated with higher lopinavir trough concentrations when all time points were evaluated. In the young cohort, among subjects with two or more measurements, there was a trend toward increasing intrasubject trough lopinavir concentrations over time. Using a nonlinear, mixed-effects population pharmacokinetic model, age was negatively associated with lopinavir clearance after adjusting for adherence. Adherence was assessed by patient self-reports; older patients missed fewer doses than younger patients ( p ¼ 0.02). No difference in grade 3-4 toxicities was observed between the two age group. Older patients have higher trough lopinavir concentrations and likely decreased lopinavir clearance.

Older HIV-infected patients on antiretroviral therapy have B-cell expansion and attenuated CD4 cell increases with immune activation reduction

“…Although these events were not independently adjudicated, they were collected prospectively according to protocol-specified definitions. Also consistent with several other studies, we previously reported that medication adherence was better in older patients, which may have accounted for the lower rate of viral load rebound that we observed in older patients [40]. …”

“…Although we previously reported no significant age group differences in grade 3 or 4 medication-associated toxicities [40], it is possible that stavudine use may have contributed to a greater risk of mitochondrial dysfunction in older patients since age is a strong risk factor for nucleoside analog-associated lipodystrophy [41], a complication that has been associated with reduced mitochondrial (mt)DNA content [42]. Previous studies have identified significant differences in mtDNA according to prior nucleoside analog exposure [43].…”

Short Communication: Aging Not Gender Is Associated with High Atazanavir Plasma Concentrations in Asian HIV-Infected Patients

“…Because the aging HIV population is increasing, few PIs have been studied in the elderly. [3][4][5] The Bristol-Myers Squibb Company (BMS) product information 3 and von Hentig et al 5 reported that age does not influence atazanavir concentrations. However, both studies were conducted in a white population.…”

Antiretroviral Treatment Efficacy and Safety in Older HIV‐Infected Adults

“…Three prospective studies assessing the PK effects of ARVs in older HIV‐infected patients were identified . A study evaluated the exposure of two alternative first‐line regimens in 12 HIV‐infected adults aged 55 years or older (mean age 59.7 ± 3.9 yrs) in an unblinded, intensive‐sampling PK study.…”