Limited information is available regarding the efficacy of antiretrovirals in people with HIV-1 and high or very high Body Mass Index (BMI). This is especially the case for the alafenamide salt of tenofovir as clinical trials have only enrolled patients with BMI ≤30 kg/m2. Lower concentrations of some antiretrovirals are expected in patients with BMI >30 kg/m2 due to potential changes in clearance and distribution of medication. This report describes an individual taking tenofovir alafenamide, emtricitabine and efavirenz in whom HIV-1 viral load was consistently undetectable (<50 copies/ml) over a 2.5 year period. During this period the patient’s BMI ranged between 59.8 and 68.1 kg/m2. Further data is required to support the efficacy of antiretrovirals in individuals with high and very high BMI.
Crum-CianfloneNRoedigerMPEberlyL, et al.Increasing rates of obesity among HIV-infected persons during the HIV epidemic. PLoS One2010; 5(4): e10106.
3.
KoetheJRJenkinsCALauB, et al.Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS research and human retroviruses. AIDS Res Hum Retroviruses2016; 32(1): 50–58. https://pubmed.ncbi.nlm.nih.gov/26352511/
SolankeTKamauFEsterhuizenT, et al.Concentrations of Efavirenz, Tenofovir, and Emtricitabine in obesity: A cross-sectional study. Journal of acquired immune deficiency syndromes1999; 91(1): 101–108. https://pubmed.ncbi.nlm.nih.gov/35972856/
MarzoliniCSabinCRaffiF, et al.Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults. AIDS2015; 29(2): 193–200. https://pubmed.ncbi.nlm.nih.gov/25426810/
9.
MadelainVLeMPChampenoisK, et al.Impact of obesity on antiretroviral pharmacokinetics and immuno-virological response in HIV-infected patients: A case–control study. J Antimicrob Chemother2017; 72: 1137–1146. https://www.hal.inserm.fr/inserm-01524383/document
10.
WatersLAhmedCAngusB, et al.BHIVA guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015 (2016 interim update). 2016.
11.
MayerKHMolinaJMThompsonMA, et al.Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. The Lancet2020; 396(10246): 239–254. https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2931065-5
12.
ChanHLYFungSSetoWK, et al. GS-US-320-0110 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol2016; 1(3): 185–195.
13.
Gilead Sciences Ltd. Email correspondence titled: Med info response to case 024385, 2022.
14.
CsajkaCMarzoliniCFattingerK, et al.Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin Pharmacol Ther2003; 73(1): 20–30.
15.
YilmazAWatsonVDickinsonL, et al.Efavirenz pharmacokinetics in cerebrospinal fluid and plasma over a 24-hour dosing interval. Antimicrob Agents Chemother2012; 56(9): 4583–4585.
16.
ENCORE 1 Study Group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): A randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet2014; 383(9927): 1474–1482.
17.
BirkusGKuttyNHeGX, et al.Activation of 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino] phenoxyphosphinyl]-methoxy]propyl]adenine (GS-7340) and other tenofovir phosphonoamidate prodrugs by human proteases. Mol Pharmacol2008; 74(1): 92–100.
18.
RuanePJDeJesusEBergerD, et al.Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1–positive adults. J Acquir Immune Defic Syndr2013; 63(4): 449–455.
19.
PodanyATBaresSHHavensJ, et al.Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide. AIDS2018; 32(6): 761–765.
20.
CerroneMAlfarisiONearyM, et al.Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide. J Antimicrob Chemother2019; 74: 1670–1678. https://pubmed.ncbi.nlm.nih.gov/30815689/
