A Randomized Comparative 96-Week Trial of Boosted Atazanavir versus Continued Boosted Protease Inhibitor in HIV-1 Patients with Abdominal Adiposity

Moyle, Graeme; Andrade-Villanueva, Jaime; Girard, Pierre Marie; Antinori, Andrea; Salvato, Patricia; Bogner, Johannes R.; Hay, Phillip; Santos, Jesús; Astier, L.; Pans, Miranda; Balogh, Agnès; Biguenet, Sophie

doi:10.3851/imp2083

Cited by 16 publications

(16 citation statements)

References 51 publications

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“…We identified a total of 27 studies for inclusion in the review: one cohort study comparing HIV-infected patients with controls [8]; 18 randomised controlled trials comparing antiretroviral regimens [3], [4], [9]–[24]; seven switching studies [25]–[31]; and one study that fulfilled the criteria for both randomised controlled trials and switching studies [32]. Our search of PubMed and Embase databases identified 3031 potential abstracts.…”

Section: Resultsmentioning

confidence: 99%

“…Fat distribution measures were done in all participants for 15 studies: one cohort study [8]; nine randomised controlled trials comparing antiretroviral regimens [4], [12], [13], [15], [16], [18], [19], [23], [32]; and five switching studies [25], [27], [29]–[31]. They were done in a subset of participants only in the remaining 12 studies [3], [9]–[11], [14], [17], [21], [22], [24], [26], [28], [33].…”

Section: Resultsmentioning

confidence: 99%

“…Two randomised controlled trials enrolled only participants with clinical or self-reported features of lipoatrophy [23], [32]; and two enrolled participants both with and without lipoatrophy [14], [21]. Three switching studies enrolled only participants with clinical or self-reported lipoatrophy [29]–[31]; and one enrolled participants with features of abdominal fat accumulation, defined as a waist-to-hip ratio of >0.9, with a waist circumference >88.2 or >75.3 cm in men and women respectively [25]. For the remaining studies it was not reported whether or not participants had features of lipodystrophy at baseline.…”

Section: Resultsmentioning

confidence: 99%

“…Eight randomised controlled trials [4], [9], [11]–[13], [18], [21], [32], and two switching studies [29], [32] evaluated NRTI-sparing regimens; four randomised controlled trials [3], [19], [24], [33], and one switching study [31] evaluated protease inhibitor (PI) versus non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens; six randomised controlled trials [3], [14], [16], [22], [23], [33], and five switching studies [27], [28], [30], [32], [34] evaluated NRTI versus NRTI regimens; two randomised controlled trials [15], [17], and one switching study [25] evaluated PI versus PI regimens; and one randomised controlled trial [10], and one switching study [26] evaluated other antiretroviral categories.…”

Section: Resultsmentioning

confidence: 99%

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Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

2013

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BackgroundLipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions.MethodsWe conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals.ResultsTwenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens.ConclusionsThere is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

2013

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“…In the REaL study, HIV-infected patients with known abdominal adiposity were continued on their current regimen, which included a ritonavirboosted PI or switched to ritonavir-boosted atazanavir. While there was a significant increase in total fat in the atazanavir group and decrease in total fat in the other PI group at 48 weeks, this difference did not persist at 96 weeks, and in addition, there were no significant differences in VAT or SAT composition or in glucose homeostasis parameters (83). In contrast, Stanley et al demonstrated a reduction in VAT among patients switching to atazanavir/ritonavir from lopinavir/ritonavir (79).…”

Section: European Journal Of Endocrinologymentioning

confidence: 91%

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

Srinivasa

Grinspoon

2014

European Journal of Endocrinology

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In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks.

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HIV-Associated Lipodystrophy: Impact of Antiretroviral Therapy

Guaraldi

Stentarelli

Zona

et al. 2013

Drugs

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In the late 1990s, reports of unusual changes in body fat distribution named 'lipodystrophy' (LD) began to appear in HIV patients mitigating the enormous enthusiasm about improvement of survival and quality of life provided by the combinations of antiretroviral (ARV) drug classes, the so-called highly active antiretroviral therapy (HAART), which had just become available at that time. The objective of this paper is to critically review the literature on LD and to discuss the impact of newer ARV agents, namely atazanavir, darunavir and raltegravir, as well as strategies of the late HAART era, including single-tablet regimens and nucleoside-sparing regimens. Studies in which LD was measured by dual-energy x-ray absorptiometry or by abdominal computed tomography or magnetic resonance imaging scan only, were included. We were unable to identify studies depicting a negative impact of drugs or ARV regimens on limb fat loss. On the contrary, a few studies identified a negative impact of atazanavir/ritonavir or darunavir/ritonavir on trunk fat increase. It should be noted that this anthropometric measure is a poor instrument since it cannot distinguish between subcutaneous and visceral fat. We conclude that presumably the body fat changes currently observed in HIV-infected patients is the net result of competing phenomena: on one side the natural history of lipohypertrophy as a result of HIV and HAART impact, and on the other side the physiological body fat changes observed in the aging population.

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A Randomized Comparative 96-Week Trial of Boosted Atazanavir versus Continued Boosted Protease Inhibitor in HIV-1 Patients with Abdominal Adiposity

Abstract: Switching to ATV/r had no demonstrable benefit on abdominal adiposity. Maintenance of efficacy, less limb fat loss and marked reduction in proatherogenic lipids was observed with ATV/r compared with continuing a PI/r regimen.

Cited by 16 publications

References 51 publications

Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

HIV-Associated Lipodystrophy: Impact of Antiretroviral Therapy

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