Effects of Discontinuing Stavudine or Protease Inhibitor Therapy on Human Immunodeficiency Virus–Related Fat Redistribution Evaluated by Dual-Energy X-Ray Absorptiometry

Tavassoli, Néda; Bagheri, Haleh; Sommet, Agnès; Delpierre, Cyrille; Marion-Latard, F.; Massip, Patrice; Aquilina, C.; Bonnet, É.; Obadia, Martine; Labau, E.; Montastruc, J. L.; Bernard, Jacques

doi:10.1592/phco.26.2.154

Cited by 10 publications

(10 citation statements)

References 28 publications

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“…However, the absolute gains were typically small in these switch studies. In the study with the largest percent gain (42%), mean leg fat by DEXA increased from 1.6 to 2.2 kg[11]. Indeed, it may be that past papers reporting percentage increases led readers to believe there was more significant recovery.…”

Section: Discussionmentioning

confidence: 99%

“…Many of the longer-term switch studies did not require the presence of lipoatrophy for entry[11–13]. When we examined HIV-infected subjects who had lipoatrophy defined as having leg SAT below the cutoff of the lowest control decile, the HIV-infected subjects had a 40% gain in leg SAT.…”

Section: Discussionmentioning

confidence: 99%

“…However, we found little recovery in those HIV-infected who started with the lowest baseline SAT relative to controls. Likewise, several of the longer term switch studies did not require lipoatrophy as an entry criterion[11–13]. While our HIV-infected participants span a wide age range (19–76 years at baseline), comparisons with controls were restricted to a narrower age range (baseline 33–45 years), which limits our ability to generalize these results to older populations.…”

Section: Discussionmentioning

confidence: 99%

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Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy

Grünfeld

Saag

Cofrancesco³

et al. 2010

Aids

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy

Grünfeld

Saag

Cofrancesco³

et al. 2010

Aids

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“…[68][69][70] For patients who do not want to change their regimen, the addition of a lipid-lowering agent is an acceptable strategy (AII). If other viable agents with presumptive antiretroviral activity are not available, then it is more appropriate to add specific antilipid therapy (AI).…”

Section: Treatment For Adult Hiv Infectionmentioning

confidence: 99%

Treatment for Adult HIV Infection

Hammer

Saag

Schechter

et al. 2006

JAMA

746

114

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Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

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“…As expected, the FMR is higher in treated HIV-infected men compared to HIV-negative controls (19), but notably even among patients with lipodystrophy who gained lower extremity fat after a change in ART regimen, few had a normalization of the FMR (51). In ART switch studies, stopping or replacing older NRTI medications often did lead to improvements in limb fat (30, 181, 223, 248), but other regimen-switches, including replacement of protease inhibitors, did not have as beneficial effects reversing visceral fat accumulation (10, 221). These findings suggest a shift in FMR in ART-treated persons is slow to resolve once established.…”

Section: Hiv Infection and Antiretroviral Therapy Alter Adipose Tissumentioning

confidence: 99%

Adipose Tissue in HIV Infection

Koethe

2017

Comprehensive Physiology

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HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling. HIV viral proteins persist in circulation and locally within adipose tissue despite suppression of plasma viremia on ART, and exposure to these proteins impairs preadipocyte maturation and reduces adipocyte expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and other genes involved in cell regulation. Several early nucleoside reverse transcriptase inhibitor and protease inhibitor antiretroviral drugs demonstrated substantial adipocyte toxicity, including reduced mitochondrial DNA content and respiratory chain enzymes, reduced PPAR-γ and other regulatory gene expression, and increased pro-inflammatory cytokine production. Newer-generation agents, such as integrase inhibitors, appear to have fewer adverse effects. HIV infection also alters the balance of CD4+ and CD8+ T cells in adipose tissue, with effects on macrophage activation and local inflammation, while the presence of latently-infected CD4+ T cells in adipose tissue may constitute a protected viral reservoir. This review provides a synthesis of the literature on how HIV virus, ART treatment, and host characteristics interact to affect adipose tissue distribution, immunology, and contribution to metabolic health, and adipocyte maturation, cellular regulation, and energy storage.

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Effects of Discontinuing Stavudine or Protease Inhibitor Therapy on Human Immunodeficiency Virus–Related Fat Redistribution Evaluated by Dual-Energy X-Ray Absorptiometry

Abstract: These data suggest that long-term withdrawal of stavudine from the antiretroviral therapy regimen may be associated with significant improvement in lipoatrophy in the lower extremities, whereas long-term protease inhibitor withdrawal did not modify fat distribution.

Cited by 10 publications

References 28 publications

Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy

Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy

Treatment for Adult HIV Infection

Adipose Tissue in HIV Infection

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