Impact of obesity on antiretroviral pharmacokinetics and immuno-virological response in HIV-infected patients: a case–control study

Madelain, Vincent; Lê, Minh Patrick; Champenois, Karen; Charpentier, Charlotte; Landman, Roland; Joly, Véronique; Yéni, Patrick; Descamps, Diane; Yazdanpanah, Yazdan; Peytavin, Gilles

doi:10.1093/jac/dkw527

Cited by 17 publications

(34 citation statements)

References 31 publications

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“…It was important to note that a limited number of patients with a BMI >40 kg/m 2 have been included in these studies. 18,20 Our study supports previous literature showing that obese patients have comparable immunologic and virologic outcomes compared to normal-weight patients. There are several limitations to the study that must be addressed.…”

Section: Discussionsupporting

confidence: 90%

“…17 In contrast, a recent case-control study of obese and nonobese patients on maintenance ART conducted in a health system with routine therapeutic drug monitoring for antiretroviral regimens demonstrated that although ART concentrations below the typical efficacy thresholds were more common in patients with obesity (>15% for EFV, nevirapine [NVP], etravirine, and raltegravir and up to 24.4% for lopinavir [LPV]), virologic failure was not associated with obesity or subtherapeutic ART concentrations after adjustment for other variables in a multivariate regression. 18 It was not reported whether ART doses were increased in response to subtherapeutic concentrations. Clinical data have supported adequate virological control in cohorts of EFV-treated patients with obesity as well.…”

Section: Discussionmentioning

confidence: 99%

“…It was important to note that a limited number of patients with a BMI >40 kg/m 2 have been included in these studies. 18,20…”

Section: Discussionmentioning

confidence: 99%

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Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection

Bunnell

Aldossari

Connor

et al. 2018

J Int Assoc Provid AIDS Care

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Background: Obesity is common among patients with HIV. The objective of this study was to characterize response to antiretroviral therapy (ART) in a cohort of obese incarcerated adults compared to a nonobese cohort. Methods: A retrospective matched cohort study was conducted in an HIV telemedicine clinic. Patients with body mass index (BMI) >30 kg/m 2 who received the same ART with >95% adherence for at least 6 months were matched to nonobese patients by age, gender, ART, CD4 count, and viral load at baseline. Results: Twenty pairs were included, with an average BMI of 24 kg/m 2 in the nonobese cohort and 35 kg/m 2 in the obese cohort. No difference was observed in the proportion of patients who achieved virologic suppression or the change in CD4 count from baseline to 6 to 12 months. Conclusion: This study revealed no differences in immunologic recovery or virologic suppression between obese and nonobese patients in an adult correctional population.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection

Bunnell

Aldossari

Connor

et al. 2018

J Int Assoc Provid AIDS Care

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“…Contrary to other studies, one of the included studies reports that obese or overweight patients had a reduced proportion of failure to second-line ART [53]. Obese HIV patients were found to have higher CD4 counts compared to normal-weight patients [96]. A higher plasma concentration of second-line regimen containing darunavir-boosted with ritonavir was revealed in obese patients [97].…”

Section: Discussionmentioning

confidence: 99%

Second-line HIV treatment failure in sub-Saharan Africa: A systematic review and meta-analysis

2019

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Background Increased second-line antiretroviral therapy (ART) failure rate narrows future options for HIV/AIDS treatment. It has critical implications in resource-limited settings; including sub-Saharan Africa (SSA) where the burden of HIV-infection is immense. Hence, pooled estimate for second-line HIV treatment failure is relevant to suggest valid recommendations that optimize ART outcomes in SSA. Methods We retrieved literature systematically from PUBMED/MEDLINE, EMBASE, CINAHL, Google Scholar, and AJOL. The retrieved studies were screened and assessed for eligibility. We also assessed the eligible studies for their methodological quality using the Joanna Briggs Institute’s appraisal checklist. The pooled estimates for second-line HIV treatment failure and its associated factors were determined using STATA, version 15.0 and MEDCALC, version 18.11.3, respectively. We assessed publication bias using Comprehensive Meta-analysis software, version 3. Detailed study protocol for this review/meta-analysis is registered and found on PROSPERO (ID: CRD42018118959). Results A total of 33 studies with the overall 18,550 participants and 19,988.45 person-years (PYs) of follow-up were included in the review. The pooled second-line HIV treatment failure rate was 15.0 per 100 PYs (95% CI: 13.0–18.0). It was slightly higher at 12–18 months of follow-up (19.0/100 PYs; 95% CI: 15.0–22.0), in children (19.0/100 PYs; 95% CI: 14.0–23.0) and in southern SSA (18.0/100 PYs; 95% CI: 14.0–23.0). Baseline values (high viral load (OR: 5.67; 95% CI: 13.40–9.45); advanced clinical stage (OR: 3.27; 95% CI: 2.07–5.19); and low CD4 counts (OR: 2.80; 95% CI: 1.83–4.29)) and suboptimal adherence to therapy (OR: 1.92; 95% CI: 1.28–2.86) were the factors associated with increased failure rates. Conclusion Second-line HIV treatment failure has become highly prevalent in SSA with alarming rates during the 12–18 month period of treatment start; in children; and southern SSA. Therefore, the second-line HIV treatment approach in SSA should critically consider excellent adherence to therapy, aggressive viral load suppression, and rapid immune recovery.

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“…Adipocytes have consistently been shown to reduce the antiviral efficacy of TDF and TAF in vitro and analysis of adipose tissue from treated PLWH suggests that INSTIs penetrate adipose tissue, whereas the penetration of NRTIs is restricted 71 . Obesity has been reported to affect ART plasma exposure but without consequence on immunovirological control 175 .…”

Section: Role Of Artmentioning

confidence: 99%

HIV and antiretroviral therapy-related fat alterations

Koethe

Lagathu

Lake

et al. 2020

Nat Rev Dis Primers

153

144

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Adipose tissue accounts for ~20-30% of total body weight in non-obese or overweight persons and for up to 50% in individuals with obesity and is a primary energy store with important endocrine and immunomodulatory functions. Most adipose tissue depots are comprised of white fat, which is responsible for energy storage and release in response to food intake and energy demand. In humans, brown and beige fat are minor components of adipose tissue and can dissipate energy as heat. White adipocytes sequester dietary lipids in adipose tissue depots to serve as energy stores during periods of fasting and prevent toxic lipid accumulation in other tissues such as muscle, liver, pancreas and heart 1. In addition, white adipocytes have a role in glucose and lipid metabolism and respond differentially to physiological cues or metabolic stresses by releasing adipokines and lipokines that regulate energy expenditure, appetite control, glucose homeostasis, insulin sensitivity, inflammation, immune function and tissue repair 2. Although adipose tissue is mainly comprised of adipocytes, it also contains mesenchymal stem cells (which can differentiate into adipocytes, myoblasts, osteoblasts and chondroblasts), immune cells (including M1 and M2 phenotype macrophages, CD4 + T cells and CD8 + T cells) and fibroblasts, in addition to blood vessels and nerves. Fat expands owing to excess energy supply either through hypertrophy (increased size of existing adipocytes) or hyperplasia (the formation of new adipocytes from mesenchymal stem cells in adipose tissue). In obesity, hypertrophic adipocytes have different biochemical properties to smaller adipocytes, including increased lipolysis, inflammatory cytokine production and reduced secretion of anti-inflammatory adipokines, such as adiponectin, that are also involved in insulin sensi tivity 1. Such alterations in fat depots predispose to ectopic lipid accumulation and the development of comorbidities, including type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), sarcopenia, atherosclerosis and heart failure 2. During physiological ageing, fat is lost from lower limbs and increases in the trunk, alongside accumulation of senescent adipocytes that have altered adipogenic potential and increased secretion of proinflammatory cytokines 3. Fat alteration became a major concern in Western countries in the mid-1990s, when people living with HIV (PLWH) receiving combination antiretroviral therapy

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Impact of obesity on antiretroviral pharmacokinetics and immuno-virological response in HIV-infected patients: a case–control study

Abstract: 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.

Cited by 17 publications

References 31 publications

Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection

Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection

Second-line HIV treatment failure in sub-Saharan Africa: A systematic review and meta-analysis

HIV and antiretroviral therapy-related fat alterations

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