Weight Gain Associated With Integrase Stand Transfer Inhibitor Use in Women

Kerchberger, Anne Marie; Sheth, Anandi N.; Angert, Christine D.; Mehta, C. Christina; Summers, Nathan A; Ofotokun, Ighovwerha; Gustafson, Deborah; Weiser, Sheri D.; Sharma, Anjali; Adimora, Adaora A.; French, Audrey L.; Augenbraun, Michael; Cocohoba, Jennifer; Kassaye, Seble; Bolívar, Héctor; Govindarajulu, Usha; Konkle‐Parker, Deborah; Golub, Elizabeth T.; Lahiri, Cecile D.

doi:10.1093/cid/ciz853

Cited by 101 publications

(77 citation statements)

References 34 publications

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“…Works are still ongoing notably to decipher the respective impact of the local viral infection and antiretroviral treatment. The question is even more relevant with the recent description of weight gain in patients (and notably women) treated with integrase inhibitors (Norwood et al, 2017;Bourgi et al, 2019;Kerchberger et al, 2019). However, more recent data suggest an even broader impact of fat tissue infection, potentially affecting systemic secondary immune responses and contributing to the accelerated aging, two defects commonly associated with chronic HIV infection.…”

Section: Consequences Of At Infectionmentioning

confidence: 99%

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

et al. 2019

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Although white AT can contribute to anti-infectious immune responses, it can also be targeted and perturbed by pathogens. The AT's immune involvement is primarily due to strong pro-inflammatory responses (with both local and paracrine effects), and the large number of fat-resident macrophages. Adipocytes also exert direct antimicrobial responses. In recent years, it has been found that memory T cells accumulate in AT, where they provide efficient secondary responses against viral pathogens. These observations have prompted researchers to re-evaluate the links between obesity and susceptibility to infections. In contrast, AT serves as a reservoir for several persistence pathogens, such as human adenovirus Ad-36, Trypanosoma gondii, Mycobacterium tuberculosis, influenza A virus, and cytomegalovirus (CMV). The presence and persistence of bacterial DNA in AT has led to the concept of a tissuespecific microbiota. The unexpected coexistence of immune cells and pathogens within the specific AT environment is intriguing, and its impact on anti-infectious immune responses requires further evaluation. AT has been recently identified as a site of HIV persistence. In the context of HIV infection, AT is targeted by both the virus and the antiretroviral drugs. AT's intrinsic metabolic features, large overall mass, and wide distribution make it a major tissue reservoir, and one that may contribute to the pathophysiology of chronic HIV infections. Here, we review the immune, metabolic, viral, and pharmacological aspects that contribute to HIV persistence in AT. We also evaluate the respective impacts of both intrinsic and HIV-induced factors on AT's involvement as a viral reservoir. Lastly, we examine the potential consequences of HIV persistence on the metabolic and immune activities of AT.

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Section: Consequences Of At Infectionmentioning

confidence: 99%

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

et al. 2019

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“…14,16 Recent evidence also suggests greater risk of weight gain in females using INSTI-based regimens compared with males; 17 however, few studies have compared weight gain with INSTI-based regimens versus other regimens in females. 18 Therefore, the current study aimed to compare weight gain among treatment-naïve PLWH who initiated INSTI-based versus PI-based ARV regimens, including the subpopulation of female patients.…”

Section: Introductionmentioning

confidence: 99%

Real-World Assessment of Weight Change in People with HIV-1 After Initiating Integrase Strand Transfer Inhibitors or Protease Inhibitors

Chen¹,

Hardy²,

Pericone³

et al. 2020

JHEOR

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Background: Studies have shown an increase in weight among people living with human immunodeficiency virus (PLWH) who have also initiated integrase strand transfer inhibitors (INSTI). However, limited data are available regarding comparison of these changes with other antiretroviral regimens. Objective: To assess differences in weight gain after initiating INSTI- versus protease inhibitor (PI)- based regimens among treatment-naïve PLWH overall, and among a subpopulation of females only. Methods: This retrospective, observational cohort study included data from the Optum® deidentified Electronic Health Record (EHR) database. Adult PLWH who initiated INSTI- or PI-based regimens between March 1, 2016 and June 30, 2018 (index date was the first INSTI or PI prescription in this period) with ≥12-month baseline and follow-up periods, ≥1 weight measure during each period, and no prior antiretroviral use were included. The last weight measure between 12 months pre- and 30 days post-index was defined as baseline weight; the last measure between the months 4 and 12 of follow-up was defined as post-weight. Weight change was reported as absolute change and proportion of patients with increased weight. Cohorts were balanced using propensity score (PS) matching. Multivariable models were used to compare outcomes of interest. Results: After matching, 1588 patients were included (794 per cohort). At baseline, 46% were <50 years old, 26% were females, 12% had Type II diabetes and 30% had hypertension (mean baseline weight: INSTI: 83 kg (183 lb), PI: 82 kg (181 lb); P = 0.3). The mean time to follow-up weight measure was 9.3 months; INSTI initiators had a 1.3 kg (2.9 lb) greater mean weight gain (95% CI: 0.5–2.0), and a higher proportion with ≥5% weight gain (30.7% vs 26.1%; [OR=1.3, 95% CI: 1.0–1.6]) than PI initiators. Differences in weight gain between regimens were larger among females; female INSTI initiators had a 2.5 kg (5.3 lb) greater mean weight gain (95% CI: 0.7–4.2) and a higher proportion with ≥5% weight gain (37.5% vs 26.4%; OR=1.7; 95% CI [1.1–2.6]) than PI initiators. Conclusion: In a real-world setting, compared to PI-based regimens, INSTI-based regimens are associated with greater weight gain for treatment-naïve PLWH. This study may inform HIV treatment choice for health care providers.

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“…A certain rate of weight gain over time, unrelated to ART, could be expected, as even in the general population, young adult men and women have been found to gain 0.55 and 0.52 kg per year [ 26 ], respectively, with those who had a rapid and early weight gain during young adulthood being the most likely to be at risk of obesity-related conditions [ 27 ]. However, in people living with HIV infection during adulthood, a greater than expected increase of weight was noticed in cases treated with both first line [ 3 , 5 , 28 ] and switching strategies [ 7 , 29 ] with INSTIs. The reasons for the lack of this same effect among young PHIV might be due to the different characteristics of participants enrolled in this study compared to other contexts.…”

Section: Discussionmentioning

confidence: 99%

“…The weight gain seems higher in naïve, black, female people, with lower baseline weight and a higher pre-treatment HIV-RNA load [ 1 , 2 , 3 , 4 , 5 ]. On the other hand, a weight increase has also been observed after switching strategies in people with virological suppression initiating INSTIs [ 7 , 8 , 9 ]. The reasons for weight increase as well as the metabolic and cardiovascular impact of the phenomenon remain to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Switching to Integrase Inhibitors Unlinked to Weight Increase in Perinatally HIV-Infected Young Adults and Adolescents: A 10-Year Observational Study

et al. 2020

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An unexpected increase in weight gain has recently been reported in the course of integrase strand transfer inhibitors (INSTI) treatment. The possibility of this effect in people who are perinatally infected with HIV (PHIV) and thus exposed to lifelong therapy needs to be explored. This is a retrospective multicenter case-control study. Adults with PHIV followed between 2010 and 2019 in two outpatient services in Northern Italy were included if they had at least two weight measures in two successive years of observation. Patients were considered as cases if they were switched to INSTI (INSTI group), or controls if they were never exposed to INSTI (non-INSTI group). The date of the switch in cases was considered to be the baseline (T0), while it was randomly selected in controls. Mixed effect models were used to assess the weight changes in INSTI and non-INSTI groups. A total of 66 participants, 50.0% women, 92.4% Caucasian, were included. Median follow-up was 9 years (range 2–10): 4 years (range 1–8) before and 3 (range 1–9) after-T0. Mean age at the last study visit was 27.3 (±4.8) years, and mean CD4+ T-cells were 820.8 (±323.6) cells/mm3. Forty-five patients were switched to INSTI during the study, while 21 remained in the non-INSTI group. The INSTI group experienced a mean increase (pre-post T0) in bodyweight of 0.28 kg/year (95% CI − 0.29; 0.85, p = 0.338), while in the non-INSTI group, the mean increase was 0.36 kg/year (95% CI − 0.47; 1.20, p = 0.391), without a significant difference between groups (p for interaction between time and treatment regimen = 0.868). Among patients on INSTI, the weight gain after T0 was higher than pre-T0, amounting to +0.28 kg/year (95% CI − 0.29; 0.85), although this difference did not reach significance (p = 0.337). PHIV switched to an INSTI-based regimen did not experience an excessive weight gain compared to those who were treated with a non-INSTI based regimen in our cohort.

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Weight Gain Associated With Integrase Stand Transfer Inhibitor Use in Women

Cited by 101 publications

References 34 publications

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

Real-World Assessment of Weight Change in People with HIV-1 After Initiating Integrase Strand Transfer Inhibitors or Protease Inhibitors

Switching to Integrase Inhibitors Unlinked to Weight Increase in Perinatally HIV-Infected Young Adults and Adolescents: A 10-Year Observational Study

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