Dolutegravir and weight gain

Ménard, Amélie; Meddeb, Line; Tissot‐Dupont, Hervé; Ravaux, Isabelle; Dhiver, Catherine; Mokhtari, Saadia; Tomei, Christelle; Brouqui, Philippe; Colson, Philippe; Stein, Andréas

doi:10.1097/qad.0000000000001495

Cited by 138 publications

(59 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Retrospective cohort studies carried out in Brazil, the USA and France support the notion that antiretroviral therapies, especially strand transfer inhibitor-based regimens, are associated with weight increase [ 13 – 15 ]; there are, however, no published data on weight changes associated with backbone switching from a TDF- to TAF-based regimen. Unstructured, unpublished clinical observations (personal communications by colleagues/patients) indicate a potential weight gain in patients following a switch from TDF- to TAF-containing regimens.…”

Section: Introductionmentioning

confidence: 99%

A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017

et al. 2018

View full text Add to dashboard Cite

Purpose To determine whether changing from a tenofovir disoproxil fumarate (TDF)-to a tenofovir alafenamide fumarate (TAF)-containing regimen is correlated with weight changes in a human immunodeficiency virus (HIV)-positive adult cohort. Methods Retrospective analysis was conducted of data gathered from routine care in a university hospital in Munich, Germany, between July 2015 and June 2017. Data from patients' charts were extracted and a two-step approach was applied. First, weight/BMI progression within 1 year after initiation of either TDF or TAF was compared. Subsequently, weight measurements within subjects changing from a TDF-to a TAF-containing antiretroviral regimen were analyzed by means of a repeated measurements general linear model. Results After 360 days of initiating TAF, patients showed a mean (± standard deviation) percentual weight increase of 3.17 ± 0.21, whereas after 360 days of initiating TDF, patients only showed a mean (± standard deviation) percentual weight increase of 0.55 ± 0.17. The repeated measurements general linear model for within-subjects design showed a statistically significant correlation in weight after changing from a TDF to a TAF containing antiretroviral regimen. The weight difference between the two measurements while on TDF was not statistically significant, but every measure after switching to TAF was significantly higher than the previous. Conclusion Changing from a TDF-to a TAF-containing regimen is correlated with weight gain in this retrospectively analyzed real-world cohort in Munich, Germany.

show abstract

Section: Introductionmentioning

confidence: 99%

A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Expression of drug transporters by adipocytes and drug-drug interactions also likely influence ART penetration into AT. It will be important to understand how the selective penetration of these agents into AT is associated with viral persistence in AT, as well as the fat accumulation, weight gain and obesity observed in ART-treated, HIV-infected patients (Crum-Cianflone et al, 2010; Guehi et al, 2016; Koethe et al, 2016; Menard et al, 2017; Norwood et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

Adipocytes impair efficacy of antiretroviral therapy

et al. 2018

View full text Add to dashboard Cite

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue.

show abstract

“…Interestingly women had greater VAT gain on raltegravir vs PI than men, and black vs nonblack individuals [8]. The association between dolutegravir or raltegravir vs elvitegravir use and weight gain was confirmed in observational cohorts of PLWH initiated with ART [9,10,11]. Weight gain following ART initiation could be attributable in part to a "return to health" phenomenon, but is also clearly associated with individual INSTI and with personal factors as sex and ethnicity [12].…”

Section: Role Of Instimentioning

confidence: 99%

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

Lagathu

Béréziat

Gorwood

et al. 2019

Expert Opinion on Drug Safety

121

View full text Add to dashboard Cite

Introduction: Efficient antiretroviral-treatment(ART) generally allows control of HIV infection. However, persons-living-with-HIV(PLWH), when ageing, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors(NRTIs) (stavudine zidovudine) and some protease inhibitors(PIs). Recently, use of some integraseinhibitors(INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation.Lipid parameters were affected by some first-generation NRTIs, non-NRTIs(efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides.Insulin resistance is common in aging PLWH, often associated with abdominal obesity.Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population.Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.Before 2000, PLWH received first-generation ART, as nucleoside analogue reverse transcriptase inhibitors (thymidine NRTIs, stavudine, zidovudine, didanosine) and protease inhibitors (PI, indinavir, ritonavir, nelfinavir) responsible for marked adverse events on lipid and glucose metabolism and on adipose tissue. These ART were replaced by newer molecules presenting a markedly lower metabolic toxicity.However, some PLWH, previously treated with first-generation NRTIs, present long-lasting fat alterations with metabolic consequences [1]. Some contemporary ART as integrase inhibitors (INSTI), considered as metabolic-friendly, were recently associated with weight/fat gain. Therefore, there are remaining and evolving concerns regarding the effect of ART on metabolism and adipose tissue in PLWH.As a consequence of the metabolic effects of some ART, increased prevalence of cardiovascular diseases (CVD), particularly atherosclerotic CVD[2] and diabetes, has been reported, but differ according to the calendar years and the geographic area. It is important to consider the metabolic profile of each patients to adapt ART. If required, classical lipid and glucose-lowering medications are prescribed.

show abstract

Dolutegravir and weight gain

Cited by 138 publications

References 3 publications

A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017

A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017

Adipocytes impair efficacy of antiretroviral therapy

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

Contact Info

Product

Resources

About