Impact of switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the <scp>RECOMB</scp> study

Ribera, Esteban; Larrousse, María; Curran, Adrían; Negredo, Eugènia; Clotet, Bonaventura; Estrada, Vicente; Sanz, José; Berenguer, Juan; Rubio, Rafael; Pulido, Federico; Ferrer, Pedro Eitz; Maria, Alvarez; Arterburn, Sarah; Martínez, Estebán

doi:10.1111/hiv.12011

Cited by 12 publications

(12 citation statements)

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“…One limitation of our study is the small sample size, which may have compromised our results. Nevertheless, this was a subanalysis of a study designed as a pilot, exploratory trial with a sample of 80 subjects (40 in each arm) , of whom 15 were women who were excluded from our sample, and even with this sample size we were able to find statistically significant differences between and within groups.…”

Section: Discussionmentioning

confidence: 98%

“…The RECOMB study has been described elsewhere . In summary, it was a controlled, multicentre, open‐label, randomized clinical trial in virologically suppressed HIV‐1‐infected adults, comparing the impact of switching from ZDV/3TC to FTC/TDF versus continuing on ZDV/3TC on total limb fat mass assessed by DEXA over a 72‐week period.…”

Section: Methodsmentioning

confidence: 99%

“…Because HIV‐associated lipoatrophy is characterized by limb fat loss with relative trunk fat preservation, FMR may be an additional informative tool with which to measure body fat content in HIV‐infected patients, but there are almost no data on the impact of different ART regimens on FMR . We aimed to examine FMR changes in otherwise stable, virologically suppressed HIV‐infected men who switched from zidovudine/lamivudine (ZDV/3TC) to emtricitabine/tenofovir (FTC/TDF) in the RECOMB (Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada) (registered at ClinicalTrials.gov NCT00324649) study .…”

Section: Introductionmentioning

confidence: 99%

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Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio

et al. 2014

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ObjectivesFat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. MethodsA subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. ResultsSixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. ConclusionsSwitching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.Keywords: emtricitabine, fat mass ratio, lipoatrophy, tenofovir, zidovudine. Switching from TA NRTI-containing antiretroviral therapy (ART) to a non-TA NRTI regimen has been shown to be associated with an increase in limb fat over time [3][4][5][6], and avoidance or discontinuation of TA NRTIs is currently recommended to prevent or reduce body fat loss associated with the use of these drugs [7,8].Changes in limb fat mass as measured by dual X-ray absorptiometry (DEXA) have been popularly accepted as objective markers of improvement or deterioration of body fat content in clinical studies in HIV-infected patients [5,6,9,10]. Although limb fat mass change is a simple measure of the change in subcutaneous fat, it does not adequately reflect body fat distribution. Fat mass ratio (FMR) is a measure of body fat distribution that is defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass [11], and has been shown to be a good indicator of lipoatrophy and its complications, such as hypertension [12], insulin resistance and glucose disturbances [13]. A cut-off value for FMR of 1.5 has been suggested as a quantitative measure discriminating between HIV-infected patients with (FMR ≥ 1.5) and without (FMR < 1.5) clinically evident lipoatrophy [9,11], although most patients in these studies have been male. In the general population, FMR values > 1.5 are uncommo...

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio

et al. 2014

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“…Higher SAT density in tNRTI-exposed persons may represent lipoatrophic AT with decreased adipocyte size and increased fibrosis, macrophage infiltration and inflammation (18,38). Although switching from a tNRTI-based ART regimen to abacavir-or tenofovir-containing regimens has led to some improvement in limb fat quantity as measured by dual-Xray absorptiometry (39,40,41), higher SAT density after controlling for SAT quantity suggests that the detrimental AT effects of tNRTI exposure are incompletely reversible (42,43). Although observational studies have found that d4T is associated with a greater risk of SAT loss than AZT (44), given the high rate of mixed tNRTI exposure in our cohort we did not evaluate the effects of these agents on SAT quality individually.…”

Section: Discussionmentioning

confidence: 99%

Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity

Lake

Debroy

et al. 2019

European Journal of Endocrinology

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Objectives Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Design Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. Methods Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. Results HIV+ men had denser SAT (−95 vs −98 HU HIV−, P < 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV−, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV− men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P < 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. Conclusions Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

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“…However, substantial progress has been made in understanding pathogenic mechanisms such as host genetic determinants, the impact of HIV infection per se, and the role of antiretroviral therapy. Spanish researchers contributed significantly to characterizing the role of distinct drugs and ways to prevent it [ 50 , 51 ].…”

Section: Lipodystrophy Metabolic Abnormalities and Cardiovasculamentioning

confidence: 99%

AIDS Clinical Research in Spain—Large HIV Population, Geniality of Doctors, and Missing Opportunities

Soriano

Ramos

Barreiro

et al. 2018

Viruses

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The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.

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Impact of switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the RECOMB study

Cited by 12 publications

References 31 publications

Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio

Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio

Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity

AIDS Clinical Research in Spain—Large HIV Population, Geniality of Doctors, and Missing Opportunities

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