Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide

Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide Marta Santos, 1,2,3, Anais Corma-Gómez, 1,2,3 Jesica Martin-Carmona, 1,2,3 Margarita Pérez-García, 2,3 Carmen Martín-Sierra, 2,3 Pilar Rincón-Mayo, 2,3 Alejandro González-Serna, 2,3,4 Juan Antonio Pineda, 5 Luis Miguel Real, 2,3,6,a, and Juan Macías 1,2,3,5,a, 1 Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen de Valme, Sevilla, Spain, 2 Instituto de Biomedicina de Sevilla, Sevilla, Spain, 3 Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Madrid, Spain, 4 Department of Physiology, University of Sevilla, Sevilla, Spain, 5 Department of Medicine, University of Sevilla, Sevilla, Spain, and 6 Department of Medical Biochemistry, Molecular Biology and Immunology, University of Sevilla, Sevilla, Spain Background. Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH. Methods. This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m. Results. Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], −24 to 46.3) dB/m versus −4 (IQR, −35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05–1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07–2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1–1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1–1.02]; P = .027) were associated with HS at the end of follow-up. Conclusions. The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors. Keywords. HIV infection; liver fibrosis; SARS-CoV-2; steatosis; TAF. Received 11 July 2023; editorial decision 12 October 2023; accepted 27 October 2023; published online 31 October 2023 a L. M. R. and J. M. contributed equally to this work. Correspondence: Juan Macias, PhD, Unit of Infectious Diseases, Hospital Universitario Virgen de Valme, Avenida de Bellavista s/n, 41014 Sevilla, Spain ([email protected]). Open Forum Infectious Diseases ® © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons. org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permis- [email protected] https://doi.org/10.1093/ofid/ofad532 The lockdown period during the coronavirus disease 2019 (COVID-19) pandemic, designed to slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a worsening in some health parameters in the general population. Approximately 20% of the population has reported some weight gain, with a higher proportion in people with previous obesity [1], and one-fifth of patients attending weight management programs gained more than 3% of their body weight [2]. People with human immunodeficiency virus (PWH) were less likely to become infected with SARS-CoV-2 during the first waves of COVID-19 [3]. Some possible reasons included greater awareness of the risks of COVID-19 and a greater adherence to stay-at-home mandates. Less physical activity related to lockdown could also have had a greater impact on health among PWH [4]. Progressive weight gain after the achievement of human immunodeficiency virus (HIV) suppression and recovery of CD4 cell counts is worrisome. Weight gain has been associated with some antiretroviral therapy (ART), especially integrase strand inhibitors (INSTIs) [5], although the effect appears to be smaller in subjects of White race. Tenofovir alafenamide (TAF) has also been associated with weight gain in PWH [6]. Hepatic steatosis (HS) is a frequent problem in the setting of HIV infection. In fact, approximately 40% of PWH have HS [7–9]. In the general population, increased weight is correlated to the presence of HS [7]. High body mass index (BMI) is the main predictor of HS in this setting [9]. In fact, ART was not independently Hepatic Steatosis During COVID-19 Pandemic • OFID • 1 Open Forum Infectious Diseases MAJOR ARTICLE Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024 associated with HS after controlling for BMI in several crosssectional studies [9–12], conducted when tenofovir disoproxil fumarate was the tenofovir compound most commonly used. In more recent observational studies, exposure to some ART has been associated with HS in PWH, such as INSTIs and TAF [13, 14]. However, there are some conflicting data. In 1 clinical trial, switching from efavirenz to raltegravir resulted in an improvement in HS after 48 weeks [15]. In another study, treatment with INSTIs was not an independent predictor of HS after controlling for TAF exposure and BMI [16]. Other reports have shown that weight gain after switching to INSTIs did not parallel the increase in HS [17]. The impact of the COVID-19 pandemic on weight gain and HS in PWH is unknown. Due to this, we evaluated the changes in HS, measured by the controlled attenuation parameter (CAP) evaluated by vibration-controlled transient elastography (VCTE), in PWH and the factors associated with the persistence or emergence of HS during the SARS-CoV-2 pandemic. METHODS Patients and Design This cohort study included PWH seen in the infectious diseases unit of a tertiary care center in southern Spain from January 2018 to December 2021. Only PWH who self-reported a daily alcohol intake <30 g/day were included. PWH underwent an annual VCTE liver examination. Those with valid VCTE were included. At the same date as the evaluation of VCTE, PWH underwent a clinical examination that included anthropometric measurements and a blood sample draw for laboratory tests. Transient Elastography Examinations The CAP was evaluated by VCTE (FibroScan, Echosens, Paris, France), according to a standardized procedure, using the M probe [9]. Examinations were carried out by a trained operator. The CAP is a validated noninvasive tool for the evaluation of HS [18]. To consider the VCTE determinations reliable, the evaluations had to include at least 10 valid measurements, with a success rate ≥60% and an interquartile range (IQR) <30% of the median liver stiffness [19]. Endpoints and Definition Criteria The primary endpoint was the change in HS measured by CAP. We considered that HS was present if CAP value was ≥248 dB/m [20]. Overweight was defined as BMI ≥25 kg/m 2 . The FibroScan-AST (FAST) score is an index that assesses the presence of nonalcoholic steatohepatitis (NASH) and fibrosis stage 2 or greater. A FAST score ≥0.67 is considered to indicate NASH and significant fibrosis [21]. The baseline study period (ie, the period of time before the first COVID-19 lockdown) was January 2018 to March 2020 and the final study period was from April 2020 to December 2021. Statistical Analysis Categorical variables were expressed as numbers (percentage) and continuous variables as median (IQR). Ninety-five percent confidence intervals (CIs) were provided for the main rates. We used the χ 2 test for categorical variables and the Student t test for continuous variables. The McNemar test was applied for categorical related variables and the Wilcoxon test for continuous related variables. Factors associated with the presence of HS at the end of follow-up in the univariate analysis with a P value ≤.1, along with age and sex, were entered into a binary logistic regression model. These analyses were carried out using IBM SPSS 26.0 (IBM Corporation, Chicago, Illinois) and the Stata 16.1 Statistics/Data Analysis package (StataCorp, College Station, Texas). Patient Consent Statement The study was approved by the Ethics Committee of the Hospital Universitario Virgen de Valme. All PWH gave their written informed consent before being recruited into this study. This study was conducted in accordance with the Declaration of Helsinki. RESULTS Baseline Characteristics of the Population During the study period, 680 PWH followed clinical visits in our center. A total of 488 (71.8%) PWH were included in the study. The reasons for noninclusion of the rest of the subjects are shown in Figure 1. The baseline characteristics of included and not included PWH in the study are summarized in Table 1. The median time from the baseline visit to the end of follow-up was 16 (IQR, 12–24) months. The median baseline liver stiffness measurement was 5.3 (IQR, 4.3–6.9) kPa, and the median baseline CAP was 240 (IQR, 210–284) dB/m. Hepatic Steatosis During Follow-up HS was observed in 214 (43.9%) PWH at baseline and in 239 (49%) PWH at the end of follow-up (P = .036). Fifty-three (10.45%) PWH with HS at baseline presented regression of HS. The number of incident HS cases was 78 (16%). Among the overall population, there was no significant difference between the median CAP values at baseline and follow-up visits (Figure 2A). PWH who gained weight had an initial CAP of 237 (IQR, 206–277) dB/m and a final CAP of 255 (IQR, 206–277) dB/m (P < .001). Among the 294 PWH who gained weight, 127 (43.2%) had HS at baseline and 163 (55.4%) PWH at the follow-up visit (P < .001). Sixty (20.4%) PWH without HS at baseline reached a CAP value ≥248 dB/m during the study period. Among those who gained weight, 20 (7.2%) PWH had a FAST score ≥0.67 at baseline and 17 (6.1%) PWH at the follow-up visit (P = .719). The median change in CAP value among PWH taking TAF was 8.5 (IQR, −24 to 46.3) dB/m compared to −4 2 • OFID • Santos et al Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024 (IQR, −35 to 27) dB/m among those receiving TAF-free regimens (P = .003). The median change in CAP value among PWH taking INSTIs was −1.5 (IQR, −31 to 31) dB/m versus 11 (IQR, −28 to 44) dB/m among PWH not taking INSTIs (P = .152). Fifty (21.4%) of those taking TAF developed incident HS compared to 28 (11%) of those on TAF-free regimens Figure 1. Disposition of the patients. Abbreviations: HIV, human immunodeficiency virus; LS, liver stiffness; PWH, people with human immunodeficiency virus. Table 1. Baseline Characteristics of Patients Included and Not Included in the Study Characteristic Included Patients (n = 488) Not Included Patients (n = 192) P Value Male sex 405 (83) 152 (79.2) .243 Age, y, median (IQR) 55 (49–60) 54 (45–59) .001 CD4 cell count a , cells/μL 612 (447–868) 487 (445–715) .585 Undetectable HIV RNA 428 (89.5) 174 (92.6) .235 TAF 234 (48) 90 (46.9) .458 Combinations with TAF/FTC Bictegravir 130 (26.6) 41 (21.4) .153 Dolutegravir 2 (0.4) 1 (0.5) Raltegravir 15 (3.1) 5 (2.6) .744 Elvitegravir 2 (0.4) 5 (2.6) Darunavir/cobicistat 81 (16.6) 18 (9.4) .016 Rilpivirine 5 (1) 20 (10.4) <.001 Any INSTI 362 (74.2) 119 (62) .002 Dolutegravir 196 (40.2) 67 (34.9) .197 Bictegravir 131 (26.8) 41 (21.4) .138 Raltegravir 33 (6.8) 12 (6.3) .809 Elvitegravir 2 (0.4) 5 (2.6) .011 Cabotegravir 1 (0.2) … Weight, kg, median (IQR) 73 (65–80) 76 (67–84) .008 Overweight 228 (46.9) 91 (56.5) .035 HDL cholesterol, mg/dL, median (IQR) 50 (42–61) 48 (40–58) .618 Triglycerides, mg/dL, median (IQR) 112 (77–163) 113 (83–164) .319 FBG, mg/dL, median (IQR) 93 (86–102) 92 (85–100) .531 Data are presented as No. (%) unless otherwise indicated. Abbreviations: FBG, fasting blood glucose; FTC, emtricitabine; HDL, high-density lipoprotein; HIV, human immunodeficiency virus; INSTI, integrase strand inhibitor; IQR, interquartile range; TAF, tenofovir alafenamide. a Only data available for 37 people with HIV. Hepatic Steatosis During COVID-19 Pandemic • OFID • 3 Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024 (P < .001). Forty-seven (13%) of those taking INSTIs developed incident HS versus 31 (24.6%) of those not taking INSTIs (P < .001). Factors Associated With Hepatic Steatosis at the End of Follow-up The characteristics of PWH with and without HS at the end of follow-up are shown in Table 2. In the univariate analysis, age, weight gain, TAF, triglycerides, and fasting blood glucose (FBG) were associated with HS at the end of follow-up, emergent or persistent HS. After multivariate analysis, adjusted by sex and age, exposure to TAF, weight gain, hypertriglyceridemia, and FBG at the end of follow-up were associated with the persistence or progression of HS (Table 2). There was no difference in the proportion of PWH with HS at the end of follow-up between regimens according to individual INSTIs (Figure 3). Fifty-two (10.7%) PWH presented symptomatic SARS-CoV-2 infection. The frequency of HS in the follow-up visit was 29 (55.8%) for PWH who suffered COVID-19, compared with 205 (48.3%) for those without COVID-19 (P = .312). Weight Gain During Follow-up A total of 294 (60.2%) PWH gained weight. The median weight gain was 1 (IQR, −1.9 to 3.7) kg, and 149 (30.5%) PWH gained >3 kg. In the overall population, weight increased significantly Figure 2. Changes in controlled attenuation parameter (A) and weight (B) in the overall population. *Median (interquartile range). **Wilcoxon test. Abbreviation: CAP, controlled attentuaion parameter. Table 2. Characteristics of Patients With and Without Hepatic Steatosis at the End of Follow-up (n = 488) Characteristic Patients With HS (n = 239) Patients Without HS (n = 249) OR (95% CI) P Value Adjusted OR (95% CI) a P Value Male sex 198 (82.8) 207 (83.1) 0.98 (.61–1.57) .933 0.97 (.58–1.63) .721 Age, y, median (IQR) 56 (52–61) 54 (45–59) 1.03 (1.01–1.05) .001 1.03 (1.01–1.05) .007 CD4 count, cells/µL, median (IQR) 659 (462–908) 585 (443–847) 1.00 (1.00–1.00) .140 … Undetectable viral load 206 (89.2) 222 (89.9) 1.08 (.6–1.94) .802 … TAF 128 (53.6) 111 (46.4) 1.56 (1.09–2.24) .015 1.59 (1.07–2.35) .021 INSTI 175 (73.2) 64 (26.8) 0.91 (.6–1.36) .635 … Changes in weight, kg, median (IQR) 1.85 (−1.2 to 5.3) 0.25 (−2.3 to 2.32) −2.47 (−3.42 to −1.52) <.001 1.09 (1.05–1.14) <.001 HDL cholesterol, mg/dL, median (IQR) 48 (41–59) 51 (44–62) 0.99 (.98–1.00) .106 … Triglycerides, mg/dL, median (IQR) 127 (91–190) 103 (74–131) 1.00 (1.00–1.01) <.001 1.01 (1–1.01) <.001 FBG, mg/dL, median (IQR) 97 (90–107) 93 (86–102) 1.02 (1.01–1.03) .001 1.01 (1–1.02) .027 Data are presented as No. (%) unless otherwise indicated. Abbreviations: CI, confidence interval; FBG, fasting blood glucose; HDL, high-density lipoprotein; HS, hepatic steatosis; INSTI, integrase strand inhibitor; IQR, interquartile range; OR, odds ratio; TAF, tenofovir alafenamide. a Adjusted for sex, age, changes in weight, TAF, HDL, and FBG. 4 • OFID • Santos et al Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024 (Figure 2B). PWH who gained weight had an initial weight of 72.1 (IQR, 63.3–79) kg and a final weight of 75.9 (IQR, 68.2–83.2) kg (P < .001). The median weight gain was 1.4 (IQR, −1.1 to 5.1) kg among PWH who took TAF compared to 0.6 (IQR, −2.1 to 3) kg for PWH on TAF-free regimens (P = .010). Three hundred sixty-two (74.2%) PWH were receiving INSTIs. The median weight gain was 0.9 (IQR, −1.8 to 3.7) kg among PWH taking INSTIs compared with 1 (IQR, −2.1 to 3.5) kg among PWH receiving regimens without INSTIs (P = .543). DISCUSSION The frequency of HS increased during the COVID-19 pandemic among PWH. This fact was driven by weight gain during this period. However, other relevant factors had an impact on HS emergence independently of metabolic disorders. Among them, the most outstanding one was ART. Thus, exposure to TAF during the study period was associated with persistence of or progression to HS, independent of weight increase, baseline hypertriglyceridemia, or older age. To date, there have been no studies comparing HS between PWH and the general population during the pandemic. An increase in HS and weight due to poor dietary habits and sedentary lifestyles during the lockdown has been reported in the Spanish general population. The frequency of HS increased by 2% and the median weight gain was 1.6 kg from 2019 to 2020 [22]. Our study is, to the best of our knowledge, the first to evaluate changes in HS during the pandemic in PWH. We reported a 5% increase in the frequency of HS. In Spain, stay-at-home mandates during the SARS-CoV-2 pandemic, especially during the first and second waves, were more strict and prolonged than in other European countries [23]. A recent meta-analysis that included studies from different countries reported a trend in weight gain worldwide after home confinement, involving 11.1%–72.4% of people. Although weight was self-reported in all studies included in the meta-analysis, surveys conducted later, during or shortly after the lockdown, reported greater weight changes [24]. Fewer infections have been reported in PWH than in the general population in Spain [3]. This may be attributable to a tighter lockdown due to awareness of their vulnerability. PWH may have followed stay-at-home mandates more closely, resulting in more weight gain than the general population [3]. ART regimens based on TAF compared to tenofovir disoproxil fumarate have been associated with increased weight gain, particularly in the context of treatment-naive African women [25]. Starting INSTIs combinations has also been associated with more weight gain than other ART combinations in treatment-naive patients [25]. A lower weight gain has been observed after switching to INSTIs in previously treated PWH [26]. It is possible that weight gain could drive HS over time. In this regard, we found that PWH exposed to TAF were more likely to show evidence of HS, as measured by CAP, at the end of follow-up than those on TAF-free regimens during the pandemic. These differences were not observed for PWH exposed to different INSTIs in this study. This result is in agreement with a previous study that reported a relationship between TAF use and HS, but no independent association with INSTIs exposure [16]. It is noteworthy that weight gain in PWH after switching to INSTI regimens is not associated with changes in HS [17]. These data suggest a possible protective effect of INSTIs on HS that will require further investigation in the future. The relationship between HS and TAF exposure could be partly explained by weight gain related to TAF-based ART. However, this effect was independent of weight gain. Therefore, in this process not only weight gain should be involved. There may be other unknown factors associated with TAF that drive HS. Mitochondrial toxicity is a potential mechanism for nucleoside analogues. However, newer nucleosides, Figure 3. Hepatic steatosis and integrase strand inhibitors at the end of the follow-up. Hepatic Steatosis During COVID-19 Pandemic • OFID • 5 Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024 such as tenofovir, appear to be free of mitochondrial toxicity due to low affinity for binding to mitochondrial polymerase [27]. One possible explanation could be that TAF produces an alteration in liver lipid metabolism, leading to greater weight increase [28]. More studies are needed to confirm this relationship and understand their mechanisms. As expected, in this study HS was associated with weight gain and hypertriglyceridemia. In other studies, weight gain was the main predictor of HS [9]. Additionally, PWH evaluated in the present study gained more weight than the Spanish general population during the COVID-19 confinement [22]. It is important to note that in our study weight was measured directly, whereas in some studies on the general population weight was self-reported and could be underestimated [1, 2]. Triglycerides have also been associated with HS. Triglycerides, along with other metabolic factors, are known to increase the risk of HS both in the general population [29] and in PWH [30]. Our study is the first one, to our knowledge, to evaluate clinically evidenced HS and weight changes in PWH after the global SARS-CoV-2 pandemic. Most studies to date were based on selfreported changes in weight in the general population [1, 2]. In the present study, we provide data on the increase in the frequency of PWH with HS after the COVID-19 lockdown. One of the limitations of the study is that we analyzed the use of ART during the pandemic, without taking into account whether ART was previously taken by experienced PWH or started during the lockdown in treatment-naive PWH. Another limitation is that VCTE could not be reliably obtained in obese PWH and other patients due to logistic problems. Nonincluded PWH showed no differences in metabolic parameters with included PWH. Despite this, the rates of HS could have been underestimated in our study. Finally, during the pandemic, access to health services and outpatient clinics has been reduced by the decrease in the number of visits imposed by lockdowns, the fear of PWH to attend healthcare centers, mobility limitations, and selective quarantines. All of these have precluded the scheduled annual VCTE evaluation in some PWH included in the study cohort. Despite these missing data, we were able to recruit a sample of PWH from the cohort large enough to evaluate the evolution and risk factors for HS during the COVID-19 pandemic. In conclusion, HS rates among PWH have increased during the COVID-19 pandemic. Regardless of the weight gain observed during the lockdown, TAF has been independently associated with the likelihood of HS, but not INSTIs. Identifying PWH at risk of HS is relevant to prevent its progression, facilitate access to targeted treatments when available, and avoid liver complications in the future. Notes Author contributions. M. S., J. A. P., and J. M. designed the research study. M. S., A. C.-G., J. M. C., M. P.-G., P. R.-M., and C. M.-S. performed the research and analyzed the data. All authors visualized the results. J. M. provided general supervision to this research. M. S. wrote the original draft of this manuscript. A. C.-G., J. M. C., M. P.-G., P. R.-M., C. M.-S., A. G.-S., J. A. P., L. M. R., and J. M. reviewed and edited this manuscript. Acknowledgments. We are grateful to all colleagues whose work contributes to furthering knowledge about HIV. We acknowledge all the patients who contributed to this study, without whom no scientific breakthrough would be possible. Data availability. The qualitative data from which this analysis is based are available from the corresponding author upon reasonable request, only if it has undergone ethical review. Financial support. This study has been funded by Instituto de Salud Carlos III through the project PI018/00606 (co-funded by the European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). C. M.-S. is supported by CIBER (Consorcio de Investigación Biomédica en Red; reference CB21/13/ 00118), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovavión y Unión Europea NextGenerationEU. J. A. P. has received a research extension grant from the Programa de Intensificación de la Actividad de Investigación del Servicio Nacional de Salud Carlos III (I3SNS). J. M. has received a research extension grant from Acciones para el refuerzo con recursos humanos de la actividad investigadora en las Unidades Clínicas del Servicio Andaluz de Salud 2021, acción A (Intensificación anual; grant number A1-0060-2021). A. C.-G. has received a research extension grant from Acciones para el refuerzo con recursos humanos de la actividad investigadora en las Unidades Clínicas del Servicio Andaluz de Salud 2021, acción B (Clínico-Investigadores; grant number B-0061-2021). M. S. has received a Río Hortega grant from the Instituto de Salud Carlos III (grant number CM21/00263). Potential conflicts of interest. M. S. and A. C.-G. have received lecture fees from Gilead. J. M. has been an investigator in clinical trials supported by Bristol-Myers Squibb (BMS), Gilead, Merck, Sharp & Dohme (MSD), and ViiV Healthcare; has received lecture fees from Gilead, BMS, MSD, AbbVie, and ViiV Healthcare; and has received consulting fees from BMS, Gilead, and MSD. All other authors report no potential conflicts. References 1. Seal A, Schaffner A, Phelan S, et al. COVID-19 pandemic and stay-at-home mandates promote weight gain in US adults. Obesity (Silver Spring) 2022; 30:240–8. 2. Kuk JL, Christensen RAG, Kamran Samani E, Wharton S. Predictors of weight loss and weight gain in weight management patients during the COVID-19 pandemic. J Obes 2021; 2021:4881430. 3. Fernandez-Fuertes M, Corma-Gomez A, Torres E, et al. Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in southern Spain after one year of pandemic. Transbound Emerg Dis 2022; 69:e267–75. 4. Weerasuria M, Ko C, Ehm A, et al. The impact of the COVID-19 pandemic on people living with HIV in Victoria, Australia. AIDS Res Hum Retroviruses 2021; 37:322–8. 5. Buzón-Martín L. Weight gain in HIV-infected individuals using distinct antiretroviral drugs. AIDS Rev 2020; 22:158–67. 6. Mallon PWG, Brunet L, Hsu RK, et al. Weight gain before and after switch from TDF to TAF in a U.S. cohort study. J Int AIDS Soc 2021; 24:e25702. 7. Macías J, Pineda JA, Real LM. Non-alcoholic fatty liver disease in HIV infection. AIDS Rev 2017; 19:35–46. 8. Santos M, Corma-Gómez A, Fernandez-Fuertes M, et al. Burden of significant liver damage in people living with HIV after microelimination of the hepatitis C virus. J Infect 2023; 86:41–6. 9. Macías J, González J, Tural C, et al. Prevalence and factors associated with liver steatosis as measured by transient elastography with controlled attenuation parameter in HIV-infected patients. AIDS 2014; 28:1279–87. 10. Bosch B, Akpomiemie G, Chandiwana N, et al. Weight and metabolic changes after switching from tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC + DTG and TDF/FTC/efavirenz (EFV) to TDF/lamivudine (3TC)/DTG. Clin Infect Dis 2023; 76:1492–5. 11. Mohr R, Boesecke C, Dold L, et al. Return-to-health effect of modern combined antiretroviral therapy potentially predisposes HIV patients to hepatic steatosis. Medicine (Baltimore) 2018; 97:e0462. 12. Pembroke T, Deschenes M, Lebouché B, et al. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis. J Hepatol 2017; 67:801–8. 6 • OFID • Santos et al Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024 13. Kirkegaard-Klitbo DM, Fuchs A, Stender S, et al. Prevalence and risk factors of moderate-to-severe hepatic steatosis in human immunodeficiency virus infection: the Copenhagen Co-morbidity Liver Study. J Infect Dis 2020; 222:1353–62. 14. Bischoff J, Gu W, Schwarze-Zander C, et al. Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART). EClinicalMedicine 2021; 40:101116. 15. Macías J, Mancebo M, Merino D, et al. Changes in liver steatosis after switching from efavirenz to raltegravir among human immunodeficiency virus–infected patients with nonalcoholic fatty liver disease. Clin Infect Dis 2017; 65:1012–9. 16. Riebensahm C, Berzigotti A, Surial B, et al. Factors associated with liver steatosis in people with human immunodeficiency virus on contemporary antiretroviral therapy. Open Forum Infect Dis 2022; 9:ofac538. 17. Gonzalez-Serna A, Macias J, Rincon J, et al. Weight gain after switching to integrase inhibitor-based ART is not associated with hepatic steatosis in HIV-infected patients. AIDS 2023; 37:2259–62 . 18. Henry L, Eberly KE, Shah D, Kumar A, Younossi ZM. Noninvasive tests used in risk stratification of patients with nonalcoholic fatty liver disease. Clin Liver Dis 2023; 27:373–95. 19. Rinaldi L, Giorgione C, Mormone A, et al. Non-invasive measurement of hepatic fibrosis by transient elastography: a narrative review. Viruses 2023; 15:1730. 20. Karlas T, Petroff D, Sasso M, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol 2017; 66:1022–30. 21. Newsome PN, Sasso M, Deeks JJ, et al. FibroScan-AST (FAST) score for the noninvasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol 2020; 5:362–73. 22. López-González ÁA, Jané BA, Comas LM, Bote SA, Miguel HMGS, Manent JIR. Impact of COVID-19 lockdown on non-alcoholic fatty liver disease and insulin resistance in adults: a before and after pandemic lockdown longitudinal study. Nutrients 2022; 14:2795. 23. Secretaría General de la Presidencia del Gobierno. Nota de la reunión del comité técnico para la desescalada 30 de abril de 2020. Available at: https://www.sanidad. gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/reuniones/30_de_ abril_de_2020.pdf. Accessed 12 March 2023. 24. Bakaloudi DR, Barazzoni R, Bischoff SC, Breda J, Wickramasinghe K, Chourdakis M. Impact of the first COVID-19 lockdown on body weight: a combined systematic review and a meta-analysis. Clin Nutr 2022; 41:3046–54. 25. Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis 2020; 71:1379–89. 26. Van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide–based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: phase 3, randomized, noninferiority TANGO study. Clin Infect Dis 2020; 71:1920–9. 27. Hunt M, McNiff MM, Vincent AE, Sabin C, Winston A, Payne BAI. Skeletal muscle mitochondrial dysfunction in contemporary antiretroviral therapy: a single cell analysis. AIDS 2022; 36:1927–34. 28. Martini S, Maggi P, Gervasoni C, et al. Dynamics of lipid profile in antiretroviralnaive HIV-infected patients, treated with TAF-based regimens: a multicenter observational study. Biomedicines 2022; 10:3164. 29. Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol 2012; 47:586–95. 30. Kalligeros M, Vassilopoulos A, Shehadeh F, et al. Prevalence and characteristics of nonalcoholic fatty liver disease and fibrosis in people living with HIV monoinfection: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023; 21:1708–22. Hepatic Steatosis During COVID-19 Pandemic • OFID • 7 Downloaded from https://academic.oup.com/ofid/article/10/11/ofad532/7334616 by Sevilla Psych Lib B21 user on 04 April 2024