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Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy.
Bourgi K, Rebeiro PF, Turner M, Castilho JL, Hulgan T, Raffanti SP, Koethe JR, Sterling TR
(2020) Clin Infect Dis 70: 1267-1274
MeSH Terms: Adult, Female, HIV Infections, HIV Integrase Inhibitors, Heterocyclic Compounds, 3-Ring, Humans, Male, Oxazines, Piperazines, Pyridones, Reverse Transcriptase Inhibitors, Weight Gain
Show Abstract · Added December 11, 2019
BACKGROUND - Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)-based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens.
METHODS - Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)-, and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals.
RESULTS - Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant.
CONCLUSIONS - Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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12 MeSH Terms
Factors Associated With Insulin Resistance in Adults With HIV Receiving Contemporary Antiretroviral Therapy: a Brief Update.
Hulgan T
(2018) Curr HIV/AIDS Rep 15: 223-232
MeSH Terms: Adult, Anti-HIV Agents, HIV, HIV Infections, HIV Integrase Inhibitors, HIV Protease Inhibitors, Humans, Hyperglycemia, Inflammation, Insulin Resistance, Mitochondria, Obesity
Show Abstract · Added December 11, 2019
PURPOSE OF REVIEW - This narrative review summarizes recent data on factors associated with insulin resistance (IR) in adults with HIV, including contemporary antiretroviral therapy (ART).
RECENT FINDINGS - IR remains common in persons with HIV, even those receiving contemporary ART. Generalized and abdominal obesity and ectopic fat are correlates of IR, and emerging data have identified associations with biomarkers of inflammation and immune activation. Small studies suggest associations between mitochondria and IR. In ART-naïve individuals, IR increased within 4 weeks of starting ART in persons receiving contemporary boosted protease inhibitors or an integrase inhibitor. The importance of IR in non-diabetic persons with HIV will continue to grow as the population ages and obesity increases. Non-invasive estimates of IR appear to perform well in persons with HIV, but clinically relevant cutoffs are uncertain. Unexpected metabolic effects of newer HIV integrase inhibitors have been reported; thus, careful observation for and studies of IR are still warranted.
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Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor-Based Regimens.
Norwood J, Turner M, Bofill C, Rebeiro P, Shepherd B, Bebawy S, Hulgan T, Raffanti S, Haas DW, Sterling TR, Koethe JR
(2017) J Acquir Immune Defic Syndr 76: 527-531
MeSH Terms: Adult, Alkynes, Benzoxazines, Cohort Studies, Cyclopropanes, Female, HIV Infections, HIV Integrase Inhibitors, Humans, Male, Middle Aged, Retrospective Studies, Reverse Transcriptase Inhibitors, Weight Gain
Show Abstract · Added March 14, 2018
BACKGROUND - With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy, persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients who switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression who switched from EFV/TDF/FTC to an INSTI-containing regimen.
METHODS - We performed a retrospective observational cohort study among adults on EFV/TDF/FTC for at least 2 years who had virologic suppression. We assessed weight change over 18 months in patients who switched from EFV/TDF/FTC to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen versus those on EFV/TDF/FTC over the same period. In a subgroup analysis, we compared patients switched to DTG/ABC/3TC versus raltegravir- or elvitegravir-containing regimens.
RESULTS - A total of 495 patients were included: 136 who switched from EFV/TDF/FTC to an INSTI-containing regimen and 34 switched to a PI-containing regimen. Patients switched to an INSTI-containing regimen gained an average of 2.9 kg at 18 months compared with 0.9 kg among those continued on EFV/TDF/FTC (P = 0.003), whereas those switched to a PI regimen gained 0.7 kg (P = 0.81). Among INSTI regimens, those switched to DTG/ABC/3TC gained the most weight at 18 months (5.3 kg, P = 0.001 compared with EFV/TDF/FTC).
CONCLUSION - Adults living with HIV with viral suppression gained significantly more weight after switching from daily, fixed-dose EFV/TDF/FTC to an INSTI-based regimen compared with those remaining on EFV/TDF/FTC. This weight gain was greatest among patients switching to DTG/ABC/3TC.
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14 MeSH Terms
Interrogating HIV integrase for compounds that bind--a SAMPL challenge.
Peat TS, Dolezal O, Newman J, Mobley D, Deadman JJ
(2014) J Comput Aided Mol Des 28: 347-62
MeSH Terms: Computer-Aided Design, Drug Design, HIV, HIV Infections, HIV Integrase, HIV Integrase Inhibitors, Humans, Models, Molecular, Protein Binding, Software
Show Abstract · Added March 20, 2014
Tremendous gains and novel methods are often developed when people are challenged to do something new or difficult. This process is enhanced when people compete against each other-this can be seen in sport as well as in science and technology (e.g. the space race). The SAMPL challenges, like the CASP challenges, aim to challenge modellers and software developers to develop new ways of looking at molecular interactions so the community as a whole can progress in the accurate prediction of these interactions. In order for this challenge to occur, data must be supplied so the prospective test can be done. We have supplied unpublished data related to a drug discovery program run several years ago on HIV integrase for the SAMPL4 challenge. This paper describes the methods used to obtain these data and the chemistry involved.
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10 MeSH Terms