Body composition, energy expenditure and physical activity

A longitudinal study of systemic inflammation and recovery of lean body mass among malnourished HIV-infected adults starting antiretroviral therapy in Tanzania and Zambia

Subjects

  • A Corrigendum to this article was published on 06 April 2016

Abstract

Background/Objectives:

The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013.

Subjects/Methods:

HIV-infected, ART-eligible adults with body mass index (BMI) of <18.5 kg/m2 enrolled in the NUSTART trial were eligible for this study. Anthropometric and body composition data were collected at recruitment and 6 and 12 weeks post ART and C-reactive protein (CRP) was measured at recruitment and 6 weeks. The relationships between CRP and body composition were assessed using multiple regression.

Results:

Of the 1815 trial participants, 838 (46%) had baseline and 6-week CRP measurements. Median age was 36 years, 55% were females and median CD4 count was 135 cells/μl. A one-log reduction in CRP at 6 weeks was associated with increased mid-upper arm circumference (0.45 cm; 95% CI: 0.30, 0.61), calf circumference (0.38 cm; 0.23, 0.54), waist circumference (0.98 cm; 0.59, 1.37), BMI (0.37 kg/m2; 0.24, 0.50) and fat-free mass (0.58 kg; 0.26, 0.91), but not with fat mass (0.09 kg; −0.17, 0.34). Fat-free mass gains persisted at 12 weeks and were more closely associated with 6-week CRP values than with baseline values.

Conclusions:

Reduction in CRP shortly after ART initiation was associated with higher fat-free mass gains. Further studies are warranted to determine whether interventions to reduce systemic inflammation will enhance gains in fat-free mass.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1

References

  1. 1

    Liu E, Spiegelman D, Semu H, Hawkins C, Chalamilla G, Aveika A et al. Nutritional status and mortality among HIV-infected patients receiving antiretroviral therapy in Tanzania. J Infect Dis 2011; 204: 282–290.

    Article  Google Scholar 

  2. 2

    Gupta A, Nadkarni G, Yang WT, Chandrasekhar A, Gupte N, Bisson GP et al. Early mortality in adults initiating antiretroviral therapy (ART) in low- and middle-income countries (LMIC): a systematic review and meta-analysis. PLoS One 2011; 6: e28691.

    CAS  Article  Google Scholar 

  3. 3

    Grobler L, Siegfried N, Visser ME, Mahlungulu SS, Volmink J . Nutritional interventions for reducing morbidity and mortality in people with HIV. Cochrane Database Syst Rev 2013; 2: CD004536.

    Google Scholar 

  4. 4

    Ndekha MJ, van Oosterhout JJ, Zijlstra EE, Manary M, Saloojee H, Manary MJ . Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial. BMJ 2009; 338: b1867.

    Article  Google Scholar 

  5. 5

    Mulligan K, Harris DR, Monte D, Stoszek S, Emmanuel P, Hardin DS et al. Obesity and dyslipidemia in behaviorally HIV-infected young women: Adolescent Trials Network study 021. Clin Infect Dis 2010; 50: 106–114.

    CAS  Article  Google Scholar 

  6. 6

    Marchetti G, Cozzi-Lepri A, Merlini E, Bellistri GM, Castagna A, Galli M et al. Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count. AIDS 2011; 25: 1385–1394.

    CAS  Article  Google Scholar 

  7. 7

    Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011; 203: 780–790.

    CAS  Article  Google Scholar 

  8. 8

    Elia M, Goren A, Behrens R, Barber RW, Neale G . Effect of total starvation and very low calorie diets on intestinal permeability in man. Clin Sci (Lond) 1987; 73: 205–210.

    CAS  Article  Google Scholar 

  9. 9

    Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, Powderly WG . Increased plasma gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting. Am J Physiol 1998; 275: E577–E583.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Macallan DC, McNurlan MA, Milne E, Calder AG, Garlick PJ, Griffin GE . Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection. Am J Clin Nutr 1995; 61: 818–826.

    CAS  Article  Google Scholar 

  11. 11

    Powanda MC, Beisel WR . Metabolic effects of infection on protein and energy status. J Nutr 2003; 133: 322S–327S.

    Article  Google Scholar 

  12. 12

    Grunfeld C, Pang M, Shimizu L, Shigenaga JK, Jensen P, Feingold KR . Resting energy expenditure, caloric intake, and short-term weight change in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Am J Clin Nutr 1992; 55: 455–460.

    CAS  Article  Google Scholar 

  13. 13

    Shevitz AH, Knox TA, Spiegelman D, Roubenoff R, Gorbach SL, Skolnik PR . Elevated resting energy expenditure among HIV-seropositive persons receiving highly active antiretroviral therapy. AIDS 1999; 13: 1351–1357.

    CAS  Article  Google Scholar 

  14. 14

    van der Valk M, Reiss P, van Leth FC, Ackermans MT, Endert E, Romijn JA et al. Highly active antiretroviral therapy-induced lipodystrophy has minor effects on human immunodeficiency virus-induced changes in lipolysis, but normalizes resting energy expenditure. J Clin Endocrinol Metab 2002; 87: 5066–5071.

    CAS  Article  Google Scholar 

  15. 15

    Streat SJ, Beddoe AH, Hill GL . Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J Trauma 1987; 27: 262–266.

    CAS  Article  Google Scholar 

  16. 16

    Schwenk A, Hodgson L, Wright A, Ward LC, Rayner CF, Grubnic S et al. Nutrient partitioning during treatment of tuberculosis: gain in body fat mass but not in protein mass. Am J Clin Nutr 2004; 79: 1006–1012.

    CAS  Article  Google Scholar 

  17. 17

    Filteau S, PrayGod G, Kasonka L, Woodd S, Rehman AM, Chisenga M et al. Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial. BMC Med 2015; 13: 17.

    Article  Google Scholar 

  18. 18

    Mupere E, Malone L, Zalwango S, Chiunda A, Okwera A, Parraga I et al. Lean tissue mass wasting is associated with increased risk of mortality among women with pulmonary tuberculosis in urban Uganda. Ann Epidemiol 2012; 22: 466–473.

    Article  Google Scholar 

  19. 19

    McDermott AY, Shevitz A, Knox T, Roubenoff R, Kehayias J, Gorbach S . Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women. Am J Clin Nutr 2001; 74: 679–686.

    CAS  Article  Google Scholar 

  20. 20

    Silva M, Skolnik PR, Gorbach SL, Spiegelman D, Wilson IB, Fernandez-DiFranco MG et al. The effect of protease inhibitors on weight and body composition in HIV-infected patients. AIDS 1998; 12: 1645–1651.

    CAS  Article  Google Scholar 

  21. 21

    Olsen MF, Abdissa A, Kaestel P, Tesfaye M, Yilma D, Girma T et al. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia. BMJ 2014; 348: g3187.

    Article  Google Scholar 

  22. 22

    Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004; 200: 749–759.

    CAS  Article  Google Scholar 

  23. 23

    Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004; 200: 761–770.

    CAS  Article  Google Scholar 

  24. 24

    Sankaran S, George MD, Reay E, Guadalupe M, Flamm J, Prindiville T et al. Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J Virol 2008; 82: 538–545.

    CAS  Article  Google Scholar 

  25. 25

    Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008; 112: 2826–2835.

    CAS  Article  Google Scholar 

  26. 26

    Epple HJ, Schneider T, Troeger H, Kunkel D, Allers K, Moos V et al. Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut 2009; 58: 220–227.

    CAS  Article  Google Scholar 

  27. 27

    Welsh FK, Farmery SM, MacLennan K, Sheridan MB, Barclay GR, Guillou PJ et al. Gut barrier function in malnourished patients. Gut 1998; 42: 396–401.

    CAS  Article  Google Scholar 

  28. 28

    McMillan DC . Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 2009; 12: 223–226.

    Article  Google Scholar 

  29. 29

    Reingold J, Wanke C, Kotler D, Lewis C, Tracy R, Heymsfield S et al. Association of HIV infection and HIV/HCV coinfection with C-reactive protein levels: the fat redistribution and metabolic change in HIV infection (FRAM) study. J Acquir Immune Defic Syndr 2008; 48: 142–148.

    CAS  Article  Google Scholar 

  30. 30

    Koethe JR, Blevins M, Nyirenda C, Kabagambe EK, Shepherd BE, Wester CW et al. Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia. J Int AIDS Soc 2011; 14: 19.

    CAS  Article  Google Scholar 

  31. 31

    Furstenberg A, Davenport A . Comparison of multifrequency bioelectrical impedance analysis and dual-energy X-ray absorptiometry assessments in outpatient hemodialysis patients. Am J Kidney Dis 2011; 57: 123–129.

    Article  Google Scholar 

  32. 32

    Madec Y, Szumilin E, Genevier C, Ferradini L, Balkan S, Pujades M et al. Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries. AIDS 2009; 23: 853–861.

    Article  Google Scholar 

Download references

Acknowledgements

This study was funded by the European and Developing Countries Clinical Trials Partnership Grant No. IP.2009.33011.004. The funding body had no role in the design, conduct, interpretation or decision to publish results of this study. This study was prepared from data arising from the NUSTART trial. We are therefore grateful to the NUSTART study team that includes: principal investigator: Suzanne Filteau; senior investigators: Aase Bengaard Andersen, John Changalucha, Henrik Friis, Douglas C Heimburger, Lackson Kasonka, Paul Kelly; statisticians and other senior research fellows: John R Koethe, Daniela Manno, Natasha Larke, Andrea M Rehman, Susannah Woodd, Daniel Yilma; steering group: David Thurnham, Andrew Tomkins; Mwanza trial manager: George PrayGod; Lusaka trial managers: Molly Chisenga, Joshua Siame; Mwanza senior clinic team: Jeremiah Kidola, Denna Michael, Kelvin Mussa, Charles Masilingi, Elizabeth Fue, Eva Masesa, Neema Mpandachalo; Lusaka senior clinic team: Anne Kanunga, Likando Munalula, Brenda Kapinda, Nellie Sikanyika; laboratory technicians: Julius Mngara, George Ogweno, Piu Ikigo, Mutinta Muchimba, Memory Samwinga, Leo Beacroft, Harry Black, Celeste Gregg Smith; postgraduate students: Caroline Chisenga, Marlene Hebie, Derek Munkombwe, Gemma Sampson; administrators and data managers: Yolanda Fernandez, Gunda Wandore, Aswile Jonas, Hildah Banda Mabuda, Wakwoya Adugna; pharmacists: Stephen Makandilo, Mwangana Mubita, Jessy Mulenga. We are also grateful to nurses, data entry clerks, drivers and other support staff at both NUSTART sites.

Author information

Affiliations

Authors

Corresponding author

Correspondence to G PrayGod.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

PrayGod, G., Blevins, M., Woodd, S. et al. A longitudinal study of systemic inflammation and recovery of lean body mass among malnourished HIV-infected adults starting antiretroviral therapy in Tanzania and Zambia. Eur J Clin Nutr 70, 499–504 (2016). https://doi.org/10.1038/ejcn.2015.221

Download citation

Further reading