Weight Gain After HIV Therapy Initiation: Pathophysiology and Implications

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2023, Volume and Issue: 109(2), P. e478 - e487

Published: July 11, 2023

Abstract Rapid advances in the potency, safety, and availability of modern HIV antiretroviral therapy (ART) have yielded a near-normal life expectancy for most people living with (PLWH). Ironically, considering history HIV/AIDS (initially called “slim disease” because associated weight loss), latest dilemma faced by many starting is gain obesity, particularly Black people, women, those who commenced treatment advanced immunodeficiency. We review pathophysiology implications among PLWH on ART discuss why this phenomenon was recognized only recently, despite effective nearly 30 years. comprehensively explore theories causes, from initial speculation that simply return to health recovering wasting comparative effects newer regimens vs prior toxic agents, direct agents mitochondrial function. then ART, concomitant lipids, glucose metabolism, inflammatory markers. Finally, we intervention options limitations switching or specific within regimens, weight-gain mitigation strategies, potential hope access emerging antiobesity which are yet be evaluated population.

Language: Английский

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72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study

The Lancet HIV, Journal Year: 2022, Volume and Issue: 9(8), P. e534 - e543

Published: July 26, 2022

BackgroundLate initiation of antiretrovirals in pregnancy is associated with increased risk perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy safety dolutegravir-based compared efavirenz-based regimens mothers infants.MethodsDolPHIN-2 was a randomised, open-label trial. Pregnant women South Africa Uganda aged at least 18 years, untreated but confirmed HIV infection an estimated gestation 28 weeks, initiating antiretroviral therapy third trimester were eligible inclusion. Eligible randomly assigned (1:1) to receive either (50 mg dolutegravir, 300 tenofovir disoproxil fumarate, 200 emtricitabine or lamivudine Uganda) (fixed dose combination 600 fumarate plus therapy. The primary outcome time viral load less than 50 copies per mL measured 6, 12, 24, 48, 72 weeks Cox model adjusting CD4 cell count. Safety endpoints summarised by number infants events. This trial registered ClinicalTrials.gov, NCT03249181.FindingsBetween Jan 23 Aug 15, 2018, 280 screened inclusion, whom 268 (96%) assigned: 133 (50%) efavirenz group 135 dolutegravir group. 250 (93%; 125 [50%] group) included intention-to-treat analysis efficacy. Median 4·1 (IQR 4·0–5·1) 12·1 (10·7–13·3) (adjusted hazard ratio [HR] 1·93 [95% CI 1·5–2·5]). At postpartum, 116 (93%) 114 (91%) had mL. Of 57 (21%) severe adverse event, three (2%) five (4%) related drug (dolutegravir drug-related events one woman each suicidal ideation, suicide attempt, herpes zoster meningitis; attempt liver cirrhosis, people drug-induced injury). 136 (56%) recorded, none study drugs. In addition infections detected birth that have been previously reported, additional occurred during breastfeeding despite optimal maternal suppression serial negative tests first year life.InterpretationDolutegravir safe well tolerated, supporting updated WHO treatment recommendations pregnant women. Infant transmissions can occur persistently undetectable highlighting need continued testing.FundingUnitaid.

Language: Английский

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Cardiovascular toxicity of contemporary antiretroviral therapy

Current Opinion in HIV and AIDS, Journal Year: 2021, Volume and Issue: 16(6), P. 286 - 291

Published: Sept. 20, 2021

HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in 1990s. Earlier strategies, and integrase inhibitors preferred first-line ART have fundamentally changed cardiovascular side effects due to infection ART. This review provides an update on toxicity contemporary ART.Cardiovascular disease (CVD) risk, including heart failure, is still increased people living with (PLWH). Exposure older antiretrovirals, stavudine zidovudine, impact CVD risk through persistent changes body fat distribution years after discontinuation. Protease (PI) efavirenz associated metabolic disturbances CVD, although use decreasing worldwide. Integrase CCR5 antagonists seem negligible immediate toxicity. Weight gain newer antiretrovirals a reason for concern.CVD should be monitored carefully PLWH who were exposed first generation ART, or PIs. Registries capture events stay informed actual clinical current era rapid initiation inhibitor-based

Language: Английский

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Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes

Cells, Journal Year: 2022, Volume and Issue: 11(11), P. 1841 - 1841

Published: June 4, 2022

For people living with HIV, treatment integrase-strand-transfer-inhibitors (INSTIs) can promote adipose tissue (AT) gain. We previously demonstrated that INSTIs induce hypertrophy and fibrosis in AT of macaques humans. By promoting energy expenditure, the emergence beige adipocytes white (beiging) could play an important role by limiting excess lipid storage associated adipocyte dysfunction. hypothesized alter via beiging inhibition. Fibrosis gene expression were measured subcutaneous (SCAT) visceral (VAT) from SIV-infected, dolutegravir-treated (SIVART) macaques. Beiging capacity was assessed human stromal cells (ASCs) undergoing differentiation being exposed to dolutegravir, bictegravir, or raltegravir. Expression markers, such as positive-regulatory-domain-containing-16 (PRDM16), lower SIVART compared control macaques, whereas fibrosis-related genes higher. Dolutegravir bictegravir inhibited ASCs, shown markers cell respiration. also induced a hypertrophic insulin-resistant state pro-fibrotic phenotype. Our results indicate is involved hypoxia (revealed greater hypoxia-inducible-factor-1-alpha expression) fat fibrosis, inhibition, thus (via positive feedback), probably, further insulin resistance.

Language: Английский

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Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1–2 trial

The Lancet HIV, Journal Year: 2022, Volume and Issue: 9(5), P. e332 - e340

Published: April 27, 2022

Safe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar those adults, was safe well tolerated children.International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is phase 1-2 ongoing multicentre, open-label, non-comparative study dolutegravir. A 5 mg studied aged 4 weeks less than 6 years old, weighing at least 3 kg, HIV RNA greater 1000 copies per mL no previous treatment integrase strand transfer inhibitor recruited from IMPAACT clinical research sites Africa, the Americas, Asia. Doses were selected on basis intensive evaluation days 5-10, safety tolerability assessed up 48 weeks. The primary objectives this evaluate pharmacokinetics combination optimised background therapy establish dose achieves targeted 24-h trough concentration area under curve infants, children, adolescents HIV-1, 24 weeks, exposure 50 once daily adults. This analysis included participants treated proposed tablets two stages each three age cohorts. trial registered ClinicalTrials.gov (NCT01302847) ongoing.We 181 April 20, 2011, Feb 19, 2020; these, 96 received tablets. 73 (35, 48% female) who final median (range) 1 year (0·1 6·0), weight (minimum-maximum) 8·5 kg (3·7 18·5), plasma HIV-1 4·2 log10 (2·1 7·0), CD4% 24·0% (0·3 49·0); 64 (87·7%) treatment-experienced. within cohort (≥2 <6 years, ≥6 months <2 ≥4 months) geometric mean (ng/mL) 688, 1179, 1446, h area-under-the-curve (h·mg/L) 53, 74, 65, respectively. No grade or worse adverse events attributed dolutegravir.In study, provided drug tolerated. These data support use as first-line second-line infants HIV-1.National Institute Allergy Infectious Diseases, Eunice Kennedy Shriver National Child Health Human Development, Mental Health, ViiV Healthcare-GlaxoSmithKline.

Language: Английский

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Factors Associated With Liver Steatosis in People With Human Immunodeficiency Virus on Contemporary Antiretroviral Therapy

Open Forum Infectious Diseases, Journal Year: 2022, Volume and Issue: 9(11)

Published: Oct. 14, 2022

Given the impact of new antiretroviral drugs on weight and metabolic parameters, their potential contribution to development liver steatosis is concern. We investigated determinants in patients therapy (ART) Swiss HIV Cohort Study (SHCS).Between 2019 2021, we measured stiffness controlled attenuation parameter (CAP) using transient elastography consecutive SHCS participants at Bern University Hospital. Individuals with viral hepatitis coinfection pregnant women were excluded. used multivariable logistic regression explore factors associated steatosis.Of 416 participants, 113 (27.2%) female, median age was 51 years (interquartile range [IQR], 43-59), 305 (73.3%) European origin, 212 (51.0%) overweight/obese (body mass index [BMI] ≥25 kg/m2). Liver (CAP ≥248 dB/m) present 11 (5.2%) whom had significant fibrosis or cirrhosis. One hundred seventy-nine (43.0%) met criteria for metabolic-associated fatty disease (MAFLD). Among 64 individuals a BMI <25 kg/m2 steatosis, 31 (48.4%) MAFLD. In analyses, (adjusted odds ratio, 5.76; 95% confidence interval, 3.57-9.29), ≥50 (1.88, 1.14-3.09), origin (3.16, 1.69-5.89), current use tenofovir alafenamide (1.70, 1.08-2.69) steatosis. Exposure integrase inhibitors not (0.83, 0.51-1.37).Our findings suggest high prevalence among people (PWH) ART Switzerland. addition established risk factors, hepatic

Language: Английский

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Evidence gaps on weight gain in people living with HIV: a scoping review to define a research agenda

BMC Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(1)

Published: April 14, 2023

Combined antiretroviral therapy (cART) dramatically improved survival in people living with HIV (PLWH) but is associated weight gain (WG), raising concern for a possible obesity epidemic PLWH. This scoping review aims to identify the gaps existing evidence on WG PLWH and generate future research agenda.This was conducted according methodology studies reported PRISMA Extension Scoping Review checklist. Articles published English last 10 years indexed Pubmed, WHO Global Index Medicus, or Embase were searched using specific queries focused PLWH.Following selection process, 175 included articles reviewed search available four topics: (I) definition of PLWH, (II) pathogenesis (III) impact ART WG, (IV) correlation clinical outcomes. A summary data enabled us clearly define following agenda: develop data-driven noninvasive assessment methods body fat composition; further investigate interaction between HIV/cART immunity, metabolism, adipose tissue; establish role individual drugs WG; clarify independent cART, HIV, metabolic factors events.The proposed agenda may help fill knowledge that have emerged from this review.

Language: Английский

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Effect of dolutegravir-based versus efavirenz-based antiretroviral therapy on excessive weight gain in adult treatment-naïve HIV patients at Matsanjeni health center, Eswatini: a retrospective cohort study

AIDS Research and Therapy, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 7, 2024

Abstract Background There is limited data on dolutegravir (DTG)-associated weight gain from settings with a dual burden of HIV and overnutrition. Methods In Eswatini (at Matsanjeni), among 156 160 adult patients DTG-based EFV-based antiretroviral therapy (ART), respectively, we studied excessive (BMI at 24 months ART greater than baseline ≥25 kg/m 2 ). Results The median BMI increase in was 1.09 (IQR:-0.28,3.28) compared to 0.20 (IQR:-0.85,2.18) ( p value = 0.001). predicted (aOR 2.61;95% CI:1.39–4.93). Conclusion Practitioners should consider regimens as one the risk factors for overweight/obesity.

Language: Английский

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Body image among people living with HIV: A systematic review and narrative synthesis

Body Image, Journal Year: 2025, Volume and Issue: 53, P. 101880 - 101880

Published: April 18, 2025

Language: Английский

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Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

Clinical Pharmacokinetics, Journal Year: 2022, Volume and Issue: 61(5), P. 619 - 635

Published: April 11, 2022

Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity mortality. In HIV, sufficient antiretroviral exposure activity should always be maintained prevent development of resistance disease progression. However, bariatric procedures bring various gastrointestinal modifications including changes in gastric volume, acidity, emptying time, enterohepatic circulation delayed entry bile acids. These alterations may affect many aspects pharmacokinetics. Some drug characteristics result subtherapeutic potential related risk treatment failure resistance. Antiretrovirals that require low pH, administration fatty meals, longer intestinal exposure, an recirculation for their absorption most impacted by procedures. Additionally, some antiretrovirals can interact polyvalent cations supplements or drugs inhibiting acid, thereby preventing use as these comedications are commonly prescribed post-bariatric surgery. Predicting pharmacokinetics on basis solely proved challenging, therefore pharmacokinetic studies remain crucial this population. Here, we discuss general implications outcomes well properties relevant choice special patient summarise evaluated Finally, performed a comprehensive analysis theoretical considerations published pharmacodynamic data provide recommendations undergoing

Language: Английский

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