L.B. Mulenga1,2,3, P. Musonda1, L. Chirwa2, M. Siwingwa1,2, S. Suwilanji1,2, A. Mweemba1,2,3, H. Phiri3, D. Phiri3, P.L Mulenga3, G. Munthali3, A. Shibemba1,2,3, J. Todd4, S. Nzala1, J. Mulwanda3, C. Kankasa1,2, W.Gong5, J.R. Koethe5, L. Hachaambwa1,2,6, C.Claassen1,2,6, M. Vinikoor1,7,8, D.C. Heimburger5, C.W. Wester5
Insulin Resistance is Associated with Higher Plasma Viral Load Among HIV-Positive Adults Receiving Longer-Term (1 Year) Combination Antiretroviral Therapy (ART)
Table 1: Characteristics of Patients With and Without Insulin Resistance
Figure 1: Insulin Resistance, Inflammation and Viral Resistance
CONCLUSION
• Patients with non-viral suppression (VL>20 copies/mL) at 12 months of first line ART had increased likelihood of Insulin
Resistance (IR) compared to those who were viral suppression (VL<20 copies/mL)
• There was good evidence to suggest that the proportion of those with viral suppression and IR was less than those with non-viral suppression and no IR
• IR was further strongly associated with inflammatory markers CRP and TNF-alpha
• Further investigations are warranted to determine if this positive association between IR and VL is causally related, and if so in which direction. Further interrogate possible role of anti-
inflammatory agents
1University of Zambia School of Medicine, Division of Infectious Diseases, Lusaka, Zambia, 2University Teaching Hospital, Lusaka, Zambia, 3 Ministry of Health, Lusaka, Zambia,4London School of Hygiene and Tropical Medicine, London, United Kingdom, 5Vanderbilt University Medical Center, Vanderbilt Institute for Global Health, Nashville, TN, United States, 6 University of Maryland, Baltimore, MD, United States, 7University of Alabama at Birmingham, Birmingham, AL, United States, 8Centre for Infectious Diseases Research in Zambia
Characteristic Insulin Sensitive
(IS)
Insulin Resistance
(IR)
p-value
N=331 (70%) N=142 (30%)
Age (years) 37 (32, 44) 36 (29, 44) 0.064W
MaleFemale
155 (46.8)176 (53.4)
55 (38.7)87 (61.3) 0.104C
Waist circumference 81 (74, 88) 87 (78.5, 94 <0.0001W
Waist /Hip circumference
0.85 (0.81, 0.92) 0.99 (0.88, 1.10) <0.0001W
Visceral Fat 5 (3, 8) 11 (4, 14) <0.0001W
CD4 count 346 (221, 547) 391 (264, 593) 0.097W
Body Mass Index 21.8 (19.7, 24.7) 22.7 (20.2, 25.6) 0.046W
Total Cholesterol 4.2 (3.49, 4.80) 4.42 (3.64, 5.19) 0.085W
HDL 1.99 (1.32, 2.51) 1.00 (0.74, 1.43) <0.0001W
LDL 1.90 (1.30, 2.60) 2.24 (1.71, 2,92) 0.0003W
Triglycerides 0.95 (0.58, 1.67) 2.16 (0.94, 2.99) <0.0001W
Triglycerides/HDL 0.48 (0.28, 1.10) 1.70 (0.72, 3.77) <0.0001W
CRP 0.79 (0.47, 1.58) 2.38 (1.40, 3.49) <0.0001W
TNF-alpha 21.7 (14.9, 29.9) 33.9 (27.5, 42.2) <0.0001W
Viral Load < 20c/mL Viral Load >20c/mL
232 (70.1)99 (29.9)
82 (62.0)54 (38.0) 0.084C
Viral Load > 1,000c/mL Viral Load <1,000c/mL
19 (5.7)312 (94.3)
27 (19.0)115 (81.0) <0.0001C
LDL= Low Density Lipoprotein, HDL=Low Density Lipoprotein, CRP= C-Reactive Protein, TNF-alpha=Tumour Necrosis Factor alphaW=Wilcoxon/Mann-Whitney Test rank-sum test, C=chi squared test
Odds Ratio of Insulin ResistanceCharacteristics Unadjusted
OR (95% CI)p-value Adjusted
OR (95% CI)p-value
Age 0.98 (0.96, 1.00)
0.019 0.94 (0.89, 0.99)
0.014
Waist circumference 1.05 (1.03, 1.07)
<0.0001 1.05 (1.00, 1.11)
0.073
Hip circumference 0.97
(0.95,0.98)
<0.0001 0.96 (0.92,1.01) 0.087
Waist to Hip Ratio 24.6 (23-54.7) <0.0001Visceral Fat 1.14 (1.09,
1.19)<0.0001
CD4 count 1.00 (0.99, 1.00)
0.096
Body Mass Index 1.04 (0.99, 1.09)
0.087
Low Density Lipoprotein
1.29 (1.07, 1.56)
0.008 1.74 (1.02, 2.94)
0.041
Triglycerides 1.15 (1.06, 1.25)
0.002 1.21 (1.05, 1.40)
0.010
C-reactive protein 1.55 (1.36, 1.77)
<0.0001
Tumor necrosis factor 1.40
(0.99,1.00)
0.193 1.04 (1.01,1.07)
Viral Load < 20 c/mLViral Load >20 c/mL
Ref1.44 (0.95, 2.17)
0.0084Ref1.24 (0.84, 1.97) 0.04
Among individuals with VL<20 copies/mL, 82 out of 142 (58%) 95% CI (0.54%, 0.70%) had IR compared to 232 out of 331, (70%) 95% CI (65%, 75%) who did not have IR (p-value=0.042)
Table 2: Odds of Developing Insulin Resistance
010
2030
40
Insu
lin re
sista
nce
0 5 10 15C-reactive protein
Treatment Failure Without TRT Failure
Scatter plot of Insulin ResistanceAnd Inflammatory Markers-CRP
Presentation Number: 2249 Contact: lloyd mulenga, e-mail: [email protected]/ [email protected]
BACKGROUND
• As HIV-positive persons live longer due to the success of antiretroviral
therapy (ART) in decreasing mortality, the burden of non-communicable
diseases including diabetes mellitus (DM) is expected to rise1
• HIV is characterized by systemic inflammation, markers of which decrease
quickly following ART initiation, but typically do not normalize2
• Inflammation may be accompanied by insulin resistance (IR), and both are
implicated in the pathogenesis of DM in HIV-positive individuals3-7
• Sub-Saharan Africa accounts for almost two-thirds of the global HIV burden
but there are few reports of IR, DM and HIV in this region8,9
• We assessed the relationship between IR and viral suppression among HIV-
positive adults in the Zambian national ART program
METHODOLOGY
• We conducted a cross sectional survey among HIV-1 infected individuals at
12 months (± 3 months) of first line ART
• In order to adjust for survivor bias, nationally representative data on 12
months was collected
• Sampling of clinics was performed using systematic sampling to generate
probability proportional to proxy size samples
• All clinics providing ART by region and size along with the number of
patients on ART formed the sampling frame
• 20 clinics were selected based on the random starting-point sampling
interval and cumulative population size giving a sample size of 460
• Eligible patients had serum viral load (VL), fasting insulin, and glucose
performed
• IR was determined using Homeostatic model assessment
• We determined study design-weighted proportions proportions for each
outcome using linearized standard errors, 95% confidence intervals and
summary estimates
• Viral suppression (VS) was defined according to the detection threshold of
<20 copies/mL and treatment failure was defined as VL >1,000 copies/mL
LITERATURE CITED1. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global
estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-21. PMID 22079683
2. Deeks SG. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med 2009;17:118 –123
3. Brown TT, McComsey GA, King MS, Qaqish RB, Bernstein BM, da Silva BA. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr2009;51:554 –561
4. Brown TT, Patil SP, Jacobson LP, Margolick JB, Laffan AM, Godfrey R, Johnson J, Reynolds S, Schwartz AR, Smith PL. Association between systemic inflammation and obstructive sleep apnea in men with or at risk for HIV-infection from the Multicenter AIDS Cohort Study. Antivir Ther2009;14(Suppl. 2):A19
5. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327– 334
6. Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 2004;53:693–700
7. Spranger J, Kroke A, Mo ̈ hlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003;52:812– 817
8. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 2005;165(10):1179-84
9. Galli L, Salpietro S, Pellicciotta G, Galliani A, Piatti P, Hasson H, et al. Risk of type 2 diabetes among HIV-infected and healthy subjects in Italy. Eur J Epidemiol 2012;27(8):657-65.
FUNDINGThe study was sponsored by the 1) National Institute of Health, Fogarty International Center, grant number 1D43TW009744-01A1 through the UNZA-Vanderbilt Partnership for HIV-Nutrition Research Training (UVP) 2) Zambian Ministry of Health through the Global Fund to Fight AIDS, Tuberculosis and Malaria, 3) Bill & Melinda Gates Foundation (OPP1113667)
RESULTS