Weight Gain After ARV Initiation Correlates with Increased Inflammatory Biomarkers

E. Laidlaw1, A. Gouel-Cheron1, S. Kuriakose2, A. Pau1, A. Rupert2, M. Nason1, V. Sheikh1, J. Mican1, M. Manion1, I. Sereti11NIAID/National Institutes of Health (NIH), Bethesda, MD, USA; 2Leidos Biomedical Research, Inc., Frederick, MD, USA

• People with HIV (PWHIV), despite viral suppression on ART, are at greater risk for metabolic diseases (cardiovascular, liver, and renal diseases) possibly compounded by obesity.1,2

• Greater weight increases have been associated with lower pre-ART CD4 counts and higher viral loads (VL), and with specific ARV class.3,4,5,6

• Higher levels of IL-6 and CRP have been associated with obesity in PWHIV.7

• We hypothesized greater weight gain after ART initiation is associated with immune dysregulation and inflammation.

Background

• ART-naïve participants with advanced HIV/AIDS (CD4 < 100 cells/μL) were enrolled in a prospective study, initiated on ART, and followed for 160 weeks.

• Participants who were lost to follow-up, had VL >500 c/mL at week 160, or became pregnant were excluded from this analysis.

• Participants' BMI were calculated at week 0, 48, and 160 and were categorized as underweight/normal (BMI <25), overweight (BMI 25-30), and obese (BMI >30).

• Percent weight change from 0 to 48 weeks and from 0 to 160 weeks were grouped into changes < 0%, 0-10%, 10-30%, and >30%.

• Non-parametric testing (Kruskal-Wallis, Spearman Rank), Fisher’s exact test, and linear regression were used for all analyses.

Methods

ReferencesConclusions• Significant weight gains are observed in HIV participants starting ART at low CD4 counts

that can lead to obesity with higher levels of persistent inflammation.• Differences in regimen may be related to selection bias and should be addressed in

trials with randomized treatments.

1. Lake, JE. “The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection.” Current HIV/AIDS Reports. 18 October 2017. 2. Justice AC, Erlandson KM, Miotti PG, et al. Can Biomarkers Advance HIV Research and Care in the ART Era? Journal of Infectious Disease. 2017 November 20. Jix586.3. Bhagwat P, Ofotokun I, McComsey GA et al. “Predictors of Severe Weight/Body Mass Index Gain Following Antiretroviral Initiation.” CROI. UCLA, ACTG. Seattle, Washington. 13-16 February 2017. Poster Presentation: #695.4. Mascolini M. Bigger Weight Gains with Contemporary PI Regimens than with NNRTIs or INIs. 16th European AIDS Conference. October 2017.5. Norwood J, Turner M, Bofill C, et al. Weight Gain in Persons with HIV Switched from Efavirenz-Based to Integrase Strand Transfer Inhibitor-Based Regimens. Journal of Acquired Immune Deficiency Syndrome. 2017 December 15;

76(5):527-531.6. Taramasso L, Ricci E, Menzaghi B, et al. Weight Gain: A Possible Side Effect of All Antiretrovirals. Open Forum Infect Dis. 2017 Nov 3;4(4):ofx239.7. Conley LJ, Bush TJ, Rupert AW, Sereti I, et al. “Obesity is associated with greater inflammation and monocyte activation among HIV-infected adults receiving antiretroviral therapy. AIDS. 23 October 2015. 29 (16): 2201-7.

Results

TUPEB121

Characteristics N = 143

SexMale, n (%)Female, n (%)

103 (72%)40 (28%)

Age pre-ART (yrs), median (IQR)

39 (31; 46)

RaceBlack, n (%)White, n (%)Multiple Races, n (%)Unknown, n (%)Indian/Alaskan Native, n (%)

78 (55%)48 (33%)11 (8%)5 (3%)1 (1%)

EthnicityNot Hispanic/Latino, n (%)Hispanic/Latino, n (%)

86 (61%)55 (39%)

BMI, median (IQR) 23.5 (20.7; 26.0)

Cholesterol (mg/dL), median (IQR)

TotalTriglyceridesHDLLDL

147 (123; 175)144 (100; 198)

35 (26;46)84 (62;104)

CD4 (cells/microliter), median (IQR) 22 (9; 50)

Viral Load (log 10 copies/ml), mean (IQR) 5.12 (4.69; 5.5)

ARV Class Initiated at week 0NNRTI, n (%)PI, n (%)INSTI, n (%)

91 (63.6%)41 (28.7%)21 (14.7%)

Elizabeth LaidlawNIH Clinical Center10 Center Dr. Bldg. 10 Rm 8C429Bethesda, MD 20814Tel: 301-827-9717E-mail: elizabeth.laidlaw@nih.gov

Table 1. Baseline Characteristics

Table 2: Spearman Correlation of Five BiomarkersBMI W160 BMI change

Week 160 Correlation p-value Correlation p-valueIL6 0.240 0.004 0.160 0.060

CRP 0.370 <0.0001 0.220 0.009D-DIMER 0.190 0.030 0.070 0.420

sCD14 -0.190 0.023 -0.220 0.010TNF 0.180 0.037 0.100 0.280

Table 3: Multivariate Linear Regression according to weight change at week 48

Variable Correlation p-value

PI week 48 0.050 0.09

NNRTI week 48 -0.025 0.44

INSTI week 48 0.009 0.76

Other variables included in the model: baseline OI, age, CD4 and gender

• In a multivariate linear regression, adjusting for baseline OI, CD4, age, and gender, ART regimen was not significantly associated with weight change at week 48: NNRTI (p=0.44), PI (p=0.09), and INSTI (p=0.76).

• Median percent weight change was +15% (IQR 8%; 24%) at week 48 and +18% (8%; 28%) at week 160 from baseline.

• The largest weight gain occurred in the first year (average of 16.2% weight change from 0 to 48 weeks, average of 2.3% weight change from 48 to 96 weeks), which prompted further analysis at week 48.

• 143 participants were included in the analysis. Baseline characteristics are listed in Table 1.• At week 0, 52 (37%) participants were overweight or obese and at week 160, 104 (73%) participants were overweight or obese.• There was no statistically significant difference by Fisher’s exact test between weight change from baseline to week 160 and documented

opportunistic infection (p=0.980) or baseline CD4 (p=0.606).

• Regression analysis was performed on five biomarkers at week 160 (IL6, CRP, D-dimer, sCD14, and TNF) and weight change.

• CRP (p=0.009) and sCD14 (p=0.010) had a significant correlation with percent weight change over 160 weeks.

Figure 2a: CRP and Percent Weight Change Figure 2b: sCD14 and Percent Weight Change

Figure 3: Weight Change over 160 weeks

Figure 1a: Opportunistic Infection and Weight Change Figure 1b: CD4 and Weight Change

214 patients assessed for

eligibility

195 patients eligible for the

study

Excluded (n=19)- Non-compliance (n=14)- Determined ineligible (post-enrollment) (n=5)

143 patients included in this study

- Death (n=9)- Lost to follow-up (n=32)- Voluntary withdrawal (n=7)- Viral load >500 at week 160 (n=4)