Mitochondrial DNA haplogroups and weight gain following switch to integrase strand transfer inhibitor-based antiretroviral therapy

Erlandson, Kristine M.; Wu, Kun; Lake, Jordan E.; Samuels, David C.; Bares, Sara H; Tassiopoulos, Katherine; Koethe, John R.; Brown, Todd T.; Leonard, Michael; Benson, Constance A.; Haas, David W.; Hulgan, Todd

doi:10.1097/qad.0000000000002771

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…Amongst AIDS Clinical Trials Group participants, persons with European mtDNA haplogroup clade UK and African haplogroup L3 had significantly greater weight gain after switching to INSTI-based ART, especially to regimens concomitantly using TAF [20 ▪ ], which could provide a window into observed race-based differences in weight gain with INSTIs and TAF.…”

Section: Pathogenesis Underlying Advent Of Antiretroviral Therapy-ass...mentioning

confidence: 99%

Impact of Integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV

Lake

Trevillyan

2021

Current Opinion in HIV and AIDS

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Purpose of reviewObesity is increasing in people with HIV (PWH). This review aims to summarise the recent evidence investigating the associations between the use of integrase inhibitors and tenofovir alafenamide (TAF) with weight gain and the mechanisms by which this may occur. Understanding the role that antiretroviral therapies play in promoting weight gain is critical in making informed treatment decisions. Recent findingsWeight gain is common with antiretroviral therapies and can lead to significant medical complications for PWH. Antiretroviral regimens containing an integrase inhibitor in conjunction with TAF are associated with the greatest degree of weight gain. This weight gain is greatest with dolutegravir and bictegravir compared with other integrase inhibitors. Some of the measured weight gain attributed to TAF may actually reflect a loss of weight suppressant effects of tenofovir disoproxil fumarate, and thus the exact proportional contribution of TAF remains to be seen. The mechanisms by which advent of antiretroviral therapy may be promoting weight gain is still being determined but underlying genetic risks factors and gender are very important determinants of the degree of weight gained.

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Section: Pathogenesis Underlying Advent Of Antiretroviral Therapy-ass...mentioning

confidence: 99%

Impact of Integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV

Lake

Trevillyan

2021

Current Opinion in HIV and AIDS

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“…32 Indeed, a recent study has shown differences in weight gain within White, Black, or Hispanic cohorts who switch to INSTIbased regimens may be associated with differences in genetic markers related to ancestry; however, the study sample included too few people of Hispanic ethnicity to draw firm conclusions. 33 Interpretation of our results is also complicated by the inclusion of both females (25%) and males (75%) in the Hispanic study population. As mentioned previously, several studies have reported differences between genders in ARV-related weight gain.…”

Section: Discussionmentioning

confidence: 84%

Real-World Assessment of Weight Change in African American Females and Hispanics with HIV-1 After Initiating Integrase Strand-Transfer Inhibitors or Protease Inhibitors

Chen

Anderson

Pericone

et al. 2022

JHEOR

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Background: Studies have shown an increase in weight among people living with HIV (PLWH) who initiated integrase strand transfer inhibitors (INSTI). However, weight gain with INSTI-based regimens vs other regimens in females or racial/ethnic minorities is poorly understood. Objective: This study assessed differences in weight gain among treatment-naïve, female, African Americans and Hispanics after initiating INSTI-based vs protease inhibitor (PI)-based regimens. Methods: This retrospective, observational cohort study included data from the Optum® deidentified Electronic Health Record Database. Female African Americans or Hispanics initiating INSTI- or PI-based regimens between January 1, 2015, and December 31, 2018 (first prescription was index date), with ≥12-month baseline and follow-up periods, ≥1 weight measure during each period, and no prior antiretroviral (ARV) use were included. Inverse probability of treatment weighting was used to reduce selection bias and improve cohort comparability. Multivariable models were used to compare absolute weight/body mass index (BMI) changes and proportion of patients with weight/BMI increases from pre- to post-index (last measure between the 4th and 12th months post-index). Results: Weighted cohorts included 3407 African American females (INSTI, 1704; PI, 1703) and 3711 Hispanics (INSTI, 1865; PI, 1846) PLWH. Mean time to follow-up weight measure was ~9.5 months. Among female African Americans, INSTI initiators had a 1.5 kg greater mean weight gain (2.1 kg vs 0.6 kg; P = 0.033), and a higher proportion with ≥5% weight gain (32% vs 29%; odds ratio [OR]=1.2; 95% CI [1.0-1.4]) than PI initiators. Among Hispanics, INSTI and PI initiators had similar mean increases in weight (2.1 and 1.8 kg, respectively), but INSTI initiators had a higher proportion with ≥5% weight gain (31% vs 27%; OR=1.2; 95% CI [1.1-1.4]). Female African American INSTI initiators were more likely to shift from normal or overweight to a worse BMI classification. Hispanic INSTI initiators were less likely to shift from normal BMI to overweight but more likely to shift from normal or overweight to obese. Conclusion: In a real-world setting, INSTI-based regimens were associated with greater weight gain for treatment-naïve female African Americans, compared with PI-based regimens. Differences between regimens were less consistent for Hispanics. These results may inform ARV choice for PLWH who are at risk for ARV-related weight gain.

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“…Some studies have shown an association between ARV-related weight gain and/or body mass index changes and certain populations such as women and Black and Hispanic populations. However, further study is warranted to understand both of what predictors, if any, exist for this phenomenon, as well as the cardiovascular and metabolic implications associated with weight gain [13,[125][126][127][128][129][130].…”

Section: Safety/adverse Effectsmentioning

confidence: 99%

A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection

Zhao

Crutchley

Guduru³

et al. 2022

Retrovirology

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Integrase strand transfer inhibitors (INSTIs) have improved the treatment of human immunodeficiency virus (HIV). There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation raltegravir, elvitegravir, and second generation dolutegravir and bictegravir. The most recent INSTI, cabotegravir, is approved for (1) treatment of HIV infection in adults to replace current antiretroviral therapy in individuals who maintain virologic suppression on a stable antiretroviral regimen without history of treatment failure and no known resistance to its components and (2) pre-exposure prophylaxis in individuals at risk of acquiring HIV-1 infection. Cabotegravir can be administered intramuscularly as a monthly or bi-monthly injection depending on the indication. This long-acting combination has been associated with treatment satisfaction in clinical studies and may be helpful for individuals who have difficulty taking daily oral medications. Worldwide, second generation INSTIs are preferred for treatment-naïve individuals. Advantages of these INSTIs include their high genetic barrier to resistance, limited drug-drug interactions, excellent rates of virologic suppression, and favorable tolerability. Few INSTI resistance-associated mutations have been reported in clinical trials involving dolutegravir, bictegravir and cabotegravir. Other advantages of specific INSTIs include their use in various populations such as infants and children, acute HIV infection, and individuals of childbearing potential. The most common adverse events observed in clinical studies involving INSTIs included diarrhea, nausea, insomnia, fatigue, and headache, with very low rates of treatment discontinuation versus comparator groups. The long-term clinical implications of weight gain associated with second generation INSTIs dolutegravir and bictegravir warrants further study. This review summarizes key clinical considerations of INSTIs in terms of clinical pharmacology, drug-drug interactions, resistance, and provides perspective on clinical decision-making. Additionally, we summarize major clinical trials evaluating the efficacy and safety of INSTIs in treatment-naïve patients living with HIV as well as individuals at risk of acquiring HIV infection.

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Mitochondrial DNA haplogroups and weight gain following switch to integrase strand transfer inhibitor-based antiretroviral therapy

Cited by 13 publications

References 26 publications

Impact of Integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV

Impact of Integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV

Real-World Assessment of Weight Change in African American Females and Hispanics with HIV-1 After Initiating Integrase Strand-Transfer Inhibitors or Protease Inhibitors

A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection

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