Impact of obesity on antiretroviral pharmacokinetics and immuno-virological response in HIV-infected patients: a case–control study. (8th January 2017)

• Record Type: Journal Article
• Authors: Madelain, Vincent; Le, Minh P.; Champenois, Karen; Charpentier, Charlotte; Landman, Roland; Joly, Veronique; Yeni, Patrick; Descamps, Diane; Yazdanpanah, Yazdan; Peytavin, Gilles
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 72:Number 4(2017:Apr.)
• Page Start: 1137
• Page End: 1146
• Publication Date: 2017-01-08
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkw527
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract : Background: Obesity has high prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but few data are available for antiretroviral drugs. Objectives: In this study we aimed to explore the pharmacokinetics of antiretroviral drugs and the immuno-virological response in obese patients with HIV infection. Patients and methods: We examined data from 2009 to 2012 in our hospital's database for HIV-1-infected patients who received an antiretroviral drug (abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or raltegravir). Obese patients were defined as those with BMI ≥30 kg/m 2 and normal-weight patients as those with BMI 19–25 kg/m 2 . Plasma concentrations ( C 12/24 ) were compared for each antiretroviral drug using a Mann–Whitney test. Suboptimal dosing and virological outcome were assessed by logistic regression, adjusting on covariates. Results: We enrolled 291 obese and 196 normal-weight patients. Among the 12 analysed antiretroviral drugs, tenofovir, efavirenz and lopinavir C 12 values were significantly lower in obese than normal-weight patients: 66 versus 86 ng/mL, 1498 versus 2034 ng/mL and 4595 versus 6420 ng/mL, respectively ( P < 0.001). Antiretroviral drug C 12/24 values were more frequently below efficacy thresholds for obese than for normal-weight patients after adjustment for other covariates ( P < 0.001). Although obese patients showed a higher CD4 count than normal-weight patients (510 versus 444 cells/mm 3, P < 0.001), the groups did not differ in virological failure rate. Conclusions: This study highlights the impact of obesity on antiretroviral drug plasma exposure, but identifies no consequence of this suboptimal exposure on the immuno-virological control in this population.