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: lbmulenga@yahoo.com/ lloyd.b.mulenga.1@Vanderbilt.edu

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