Fighting fat in HIV: the role of physical activity in the modern HIV era
AR Webel1, C Horvat Davey1, D Long2, M Willig2, the PROSPER-HIV Collaborators
1Case Western Reserve University, Cleveland, OH, USA; 2University of Alabama at Birmingham, Birmingham, AL, USA
Background: Throughout the world, people living with HIV (PWH) are living longer and developing chronic comorbidities at higher rates than those without HIV infection. Ageing is associated with increased abdominal adiposity, which is also a risk factor for chronic comorbidities including cardiovascular disease, diabetes mellitus, chronic kidney disease and frailty. Additionally, PWH are at high risk for increased adiposity. In the general population, few interventions can improve adiposity in an ageing population as well as physical activity. The relationship between physical activity and adiposity in people living with well-controlled HIV is unclear. The purpose of this study is to describe the association between objectively-measured physical activity and abdominal adiposity (that is, waist circumference and waist hip ratio) in PWH.
Methods: As part of the multisite, observational PROSPER-HIV study, adults (≥18 years) living with HIV, who are on HIV antiretroviral therapy, are virally suppressed, and part of the CNICS cohort wore an Actigraph accelerometer for 7–10 days and completed duplicate, standardized measures of waist and hip circumference at one time point. Valid accelerometer data included those who wore the device for ≥10 h a day for a minimum of 4 days (that is, 1 weekend day and 3 weekdays). Physical activity intensities were classified using 2011 cut points. Demographic and medical characteristics were abstracted from the CFAR Network of Integrated Clinical Systems (CNICS) dataset. Descriptive statistics and multiple linear regressions were used to analyse the data.
Results: To date, 175 PWH have been enrolled in the PROSPER-HIV study. On average, they are 52.9 years of age (±10.5), male (68%), and Black or African American (68%). Over a week, on average, participants engaged in 37.35 (±67.78) min of moderate-to-vigorous physical activity and had an average of 13,764 (±5,482) steps per day. Participants also had 415 (±183) min of sedentary time per day. Mean waist circumference was 102.4 cm (±16.1) and the mean waist-to-hip ratio was 0.96. Controlling for age and sex, the number of steps taken per day was associated with reduced abdominal adiposity (b=-75.4; P=0.030). Relationships between moderate-vigorous physical activity, sedentary time per day and measures of abdominal adiposity were not observed (P>0.05).
Conclusions: These data suggest that physical activity reduces abdominal adiposity in ageing PWH. In particular, increasing the number of steps per day is likely an acceptable early physical activity intervention in a mostly sedentary population. Future work should investigate how to precisely tailor the amount, type and intensity of physical activity needed to reduce adiposity and, in turn, related comorbidities in PWH.
Acknowledgements: This study was supported by research grants from the National Institute of Nursing Research (5R01NR018391) and from the National Institute of Allergy and Infectious Diseases (R24AI067039).
Abstract P12
Antiviral Therapy 2019; 24 Suppl 1:A50
Weight gain in people living with HIV switched to dual therapy with dolutegravir plus rilpivirine: changes in body fat mass
P Vizcarra1, MJ Vivancos1, MJ Pérez-Elías1, A Moreno1, JL Casado1
1Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Madrid, Spain
Objectives: We investigated changes in weight and body composition, and associated factors, in virologically suppressed HIV-infected adults switching to a dolutegravir-based dual therapy.
Methods: Weight, fat mass and lean mass were measured in a prospective cohort of HIV-infected individuals switching to dolutegravir-based dual therapy using whole-body dual-energy X-ray absorptiometry (DXA; NCT02491242). Data were compared with a control group of HIV-infected adults switched to boosted darunavir-based dual therapy. Individuals with lipodystrophy, or prior exposure to integrase inhibitors were excluded.
Results: Overall, 54 individuals met the inclusion criteria (mean age 53 years, male 61%), 37 (69%) switched to dolutegravir plus rilpivirine and 17 (31%) switched to darunavir plus lamivudine. At baseline, median weight was 73 kg (standard deviation, sd 14.7) and 70 kg (sd 13.1) in the dolutegravir and darunavir group, respectively (P=0.14). After 48 weeks, weight increased by 1.80 kg (sd 3.8, +2.5%; P=0.03) in the dolutegravir group and 0.70 kg (sd 3.9; +1%; P=0.28) in the darunavir group, without significant differences between groups (P=0.45).
After a median of 16 months (IQR 11.1–22.6) of switching, DXA scan exhibited similar increases in median fat mass in trunk, arms and legs in both groups (Table 1). Fat mass ratio was unaltered, and there were no significant changes in lean mass or muscle-related index in any group. In adjusted multivariable linear regression analysis, total fat mass increase was associated with baseline fat mass (Beta, −0.19, 95% confidence interval, CI: −0.08, −0.30) and nadir CD4+ count (Beta, −0.006, 95% CI: −0.0001, −0.012).
Conclusions: Weight gain observed with dolutegravir plus rilpivirine dual therapy was significant and was related with fat mass gain in the different body compartments, with no modifications of lean mass. Nevertheless, comparable changes were observed in individuals switching to darunavir plus lamivudine. Fat mass increase was associated with baseline fat mass and immunological status.
Abstract P13
Antiviral Therapy 2019; 24 Suppl 1:A51
Body composition changes in HIV: do INSTI matter?
G Guaraldi1, J Milic1,2, A Malagoli1, C Bassoli3, F Carli1, A Raimondi1, C Mussini1
1Modena HIV Metabolic Clinic, University of Modena and Reggio Emilia, Italy; 2Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy; 3University of Modena and Reggio Emilia, Modena, Italy
Objectives: The aim was to assess weight gain (WG) and body composition changes in people living with HIV (PLWH) switching to INSTI-based regimens in comparison to INSTI-naive patients. We assessed WG impact on incidence of comorbidities.
Methods: In a prospective observational study, we included ART-experienced INSTI-naive PLWH from 2007 to 2019. Patients were divided in two groups: patients who remained INSTI-naive and patients who switched to an INSTI regimen either in 3 drugs regimens (3DR) or in 2 drug regimens (2DR). The groups were matched for sex, age, baseline BMI and switch duration. WG was defined as an annualized increase of 7% in BMI. Predictors of WG were analysed in a multivariable regression model comparing INSTI-naive 3DR to INSTI-naive 2DR, and patients who switched to INSTI either in 3DR or 2DR.
Results: A total of 1,158 PLWH (68.7% males) were analysed at baseline and at 4 years (±2.23) follow-up. Patients who switched to INSTI showed significant changes in age, BMI, waist circumference (WC), fat-free mass index (FFMI), appendicular skeletal muscle index (ASMI) and leg fat % (P<0.001). Mixed lipodystrophy, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) did not change over time. INSTI-naive showed significant changes in age, BMI, WC, FFMI, ASMI, leg fat %, sarcopenia, VAT and SAT. Higher prevalence of WG was observed in patients who switched to INSTI (68.9% versus 31.2%; P<0.001). Figure 1 describes independent predictors of WG. PLWH who experienced WG had higher incidence of T2DM (1.97 versus 1.22), CVD (1.67 versus 0.53), HTN (13.2 versus 7.07), CKD (6.82 versus 3.49), COPD (3.4 versus 1.06) cases per 100 patient-years, with the latter being the only statically significant.
(Abstract P13)
Conclusions: We observed WG both in 3DR and 2DR in INSTI-based switch. Clinical relevance of this phenomenon needs to be explored in larger cohorts.
Abstract P14
Antiviral Therapy 2019; 24 Suppl 1:A53
NRTI backbone modification impact on weight, lipids and cardiovascular risk
A Milinkovic1, W Hickey1, K McCann2, A Soler-Carracedo1, M Mazzitelli1, 3, G Moyle1, D Asboe1, A Hill4, M Boffito1, 2
1Chelsea & Westminster Hospital NHS Foundation Trust, London, UK; 2Imperial College, London, UK; 3Magna Graecia University, Catanzaro, Italy; 4University of Liverpool, UK
Purpose: Switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) may be associated with weight gain and worsening of lipid profile. It is unclear if this is related to loss of protective effect of TDF or an effect of TAF. The impact of these findings on cardiovascular risk (CVR) has not been specifically investigated.
Method: This is a retrospective data collection from clinical notes of people living with HIV, switched to TAF-based antiretroviral treatment at Chelsea and Westminster Hospital, London, without changing other regimen components. Body weight, lipid profile, blood pressure were measured and CVR scores (QRISK2-2017 and Framingham) calculated before and every 12-24 weeks after the switch.
Results: 274 patients were included in the analysis: 216 switched from TDF (group 1) and 58 switched from non-TDF-containing regimens to TAF (group 2). Mean (sd) age was 59 ±9.9 years, 88.7% were male, 75.2% Caucasian, with a BMI of 23.95 ±4.6 kg/m2 and CD4 count of 682 ±300 cells/μl at switch. Overall, weight increase 1 year post-switch to TAF was 1.7 ±6.8 kg. Statistically significant weight and cholesterol increases from baseline were observed in group 1 (1.4 ±5.6 kg, P=0.02 and 0.3 mmol/l ±1.0, P<0.05). 1 year after the switch to TAF the proportion of subjects with BMI >25 kg/m2 had risen by 10%. In a logistic regression analysis the odds of having a BMI increase >10% was associated with older age (odds ratio: 0.9; 95% CI [0.9,1.0]; P=0.02); CD4 <200 cells/μl (P=0.04) and smoking (P=0.04). QRISK2-2017 and Framingham scores remained stable (P=0.0997 and P=0.17) with no changes observed from baseline to 1-year post-switch.
Conclusions: Our real-world analysis suggests that weight and lipid increases may relate to switching away from TDF rather than the independent effect of TAF, however, long-term data in larger populations are warranted.
Abstract P15
Antiviral Therapy 2019; 24 Suppl 1:A54
Predictors of sarcopenia and its impact on components of the frailty phenotype in an Asian population living with HIV
G Lui1,2, MC Chan3, J Woo1, TY Tsang3, TC Kwok1
1Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, HKSAR; 2Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, HKSAR; 3Department of Medicine and Geriatrics, Princess Margaret Hospital, HKSAR
Objectives: We aimed to study the prevalence and predictors of sarcopenia in people living with HIV (PLWH) in Asia. The impact of sarcopenia on the components of frailty phenotype is explored in this population.
Methods: We performed a prospective observational cohort study. Adult HIV-infected patients aged ≥18 years, followed in an HIV metabolic clinic in Hong Kong were enrolled. Clinical data was collected. Dual-energy X-ray absorptiometry (DXA) scan was performed to measure body composition. Sarcopenia was defined by appendicular skeletal muscle index/ASMI (lean mass of extremities/height2) <7.0 kg/m2 in men and <5.4 kg/m2 in women according to recommendations by the Asian Working Group for Sarcopenia. The Fried frailty phenotype (unintentional weight loss, exhaustion, low physical activity, and diminished gait speed and grip strength) was assessed in a subgroup of this cohort. Multivariable binary logistic regression model was performed to determine predictors of sarcopenia. The association of sarcopenia with each component of frailty phenotype, and the association between number of deficits in frailty phenotype and ASMI were determined by Chi square and one-way ANOVA, respectively.
Results: 251 PLWH were enrolled. Mean ±sd age was 52 ±13 years, 209 (83.3%) were male and 233 (92.8%) were Chinese. The duration of HIV diagnosis was 7 (IQR 1–13) years, 83 (33.1%) had history of AIDS, median (IQR) CD4 was 490 (215–705) cells/mm3. Diabetes was present in 77 (30.7%), hypertension in 88 (35.1%), hepatitis B in 27 (10.8%) and hepatitis C in 13 (5.2%).
In this cohort, 105 (41.8%) had sarcopenia. Sarcopenia was more prevalent in Chinese, and those with hepatitis B, hepatitis C, history of AIDS, lower CD4 count, lower CD4:CD8 ratio, higher HIV RNA, lower body weight and exposure to stavudine (Table 1). Sarcopenia was not associated with age or sex. Multivariable logistic regression model showed sarcopenia was independently associated with Chinese ethnicity (adjusted odds ratio [aOR] 6.2 [95% CI 1.0,39.1]), hepatitis B (aOR 4.9 [95% CI 1.6,15.7]), body weight (aOR 0.87 [95% CI 0.84,0.91]) and exposure to stavudine (aOR 2.4 [95% CI 1.1,5.4]).
(Abstract P15)
Table. Variables associated with sarcopenia on univariate analysis
Variables
Sarcopenia N=105
No sarcopenia N=146
P
Chinese
103 (98.1%)
130 (89.0%)
0.006
Hepatitis B
17 (16.2%)
10 (6.8%)
0.018
Hepatitis C
10 (9.5%)
3 (2.1%)
0.008
History of AIDS
42 (40.0%)
41 (28.1%)
0.048
CD4 count, cells/mm3
423 [250-670]
533 [359-731]
0.007
CD4:CD8 ratio
0.54 [0.31-0.811
0.70 [0.43-0.95]
0.016
HIV RNA, copies/mL
40 [40-68]
40 [20-40]
0.002
Body weight, kg
58.1±8.0
71.4±13.8
<0.001
Exposure to stavudine
26 (24.8%)
20 (13.7%)
0.025
In a subgroup of 142 PLWH, 74 (52.1%) were pre-frail and 8 (5.6%) were frail. Among the five components of frailty phenotype, sarcopenia was associated with weak hand grip (39.4% versus 13.7%; P=0.001), low physical activity (24.2% versus 10.7%; P=0.032) and weight loss (21.9% versus 8.2%; P=0.024). A significant reduction of ASMI was observed with increasing number of deficits in the frailty phenotype (for example, 7.5 ±1.1 versus 5.7 ±1.3 kg/m2 in those with none and four deficits; P=0.001).
Conclusions: In an Asian cohort of PLWH, sarcopenia was present in 42% and was associated with Chinese ethnicity, hepatitis B, low body weight and exposure to stavudine. Sarcopenia was associated with components of the frailty phenotype.
Abstract P16
Antiviral Therapy 2019; 24 Suppl 1:A56
Body size modifies the relationship between internalized HIV stigma and pain in people with HIV in the southeastern USA
KB Crockett, B Turan
University of Alabama at Birmingham, USA
Background: Both pain and obesity have emerged as common comorbidities in the context of HIV. Meanwhile, HIV-related stigma poses a significant barrier to improving health outcomes for people with HIV, with research supporting an association between internalized HIV stigma and pain. Extant research suggests obesity is also associated with pain but may interact with other variables in its association. In the present analysis, we investigated the role of body size as a moderator of the association between internalized HIV stigma and experiences of pain.
Methods: Participants included 180 men and women with HIV who were not currently using substances and completed measures during a study visit at an HIV primary clinic located in Birmingham, Alabama. Internalized HIV stigma was measured using the self-stigma subscale of the revised HIV Stigma Scale. Height and weight measures were collected for computation of BMI. BMIs were categorized as ‘healthy weight’ (BMI=18.5–24.9), ‘overweight’ (BMI=25–29.9) and ‘obese weight’ (BMI=30+). Only two participants had underweight (BMI<18.5) and were omitted from the analysis. Current pain was reported 1 week following initial study measures using a numerical rating scale from 0: ‘no pain’ to 10: ‘worst imaginable pain’. Model covariates included participant age, sex, race, sexual orientation, socioeconomic status and time on antiretroviral medications in months.
Results: Of the participants, 31% were in the healthy weight range, 39% were in the overweight range and 30% were in the obese weight range. In the multivariable model, both internalized HIV stigma and BMI category were positively associated with pain. The interaction of stigma with weight category was significant (B=-1.02, SE=0.45, 95% CI [-1.90,-0.13]). Upon examination of simple slopes, individuals with lower BMI had a positive association between internalized HIV stigma and pain (B=1.48, SE=0.55, 95% CI [0.40,2.56]). Internalized HIV stigma was not associated with pain for people in the overweight range (B=0.46, SE=0.36, 95% CI [-0.24,1.17]) or the obese weight range (B=-0.55, SE=0.60, 95% CI [-1.73,0.62]). Significant covariates associated with pain included female sex and lower socioeconomic status. See Figure 1.
(Abstract P16)
Conclusions: Our findings provide further evidence that internalization of negative societal attitudes regarding HIV relate to greater perceptions of bodily pain. However, that association may depend on body size and composition. Further research is needed to understand individuals’ perceptions of body size in relation to HIV stigma, which can inform health communication for patients with HIV managing their weight or pain.
