Intimate Partner Violence is Associated with Increased CD4+ T-Cell Activation Among HIV-Negative High-Risk Women

Main Article Content

Ameeta Shivdas Kalokhe
Chris C. Ibegbu
Surinder P. Kaur
Rama R. Amara
Mary E. Kelley
Carlos del Rio
Rob Stephenson


Background: Biological pathways mediating the link between intimate partner violence (IPV) and increased HIV risk remain unexplored. We hypothesized that IPV-induced stress negatively affects HIV systemic immune defenses and aimed to evaluate whether IPV was associated with immune profiles linked to HIV susceptibility: CD4 activation and diminished regulatory T-cell (Treg) frequency.

Methods: Seventy-five HIV-negative high-risk women were surveyed regarding their IPV experience. They provided blood, urine, and (if present) genital ulcer samples for cortisol, immune assays, and STI testing. Using flow cytometry, we assessed activated CD4+ T-cell (%HLA-DR+/CD38+) and Treg (%CD4+CD25+FoxP3+) frequencies and phenotyping. Nonparametric tests evaluated the association between IPV and immune outcomes. Multivariate regression explored confounding and moderation of the IPV-CD4 activation pathway.

Results: Lifetime IPV was associated with increased CD4+ activation (r=0.331, P=0.004), a shift in CD4+ phenotype from naïve to effector memory (r=0.343, P=0.003), and a decrease in naive (%HLA-DR+/CD45RA-) Treg frequency (r=-0.337, P=0.003). Experiencing IPV over the past year had similar trends. After controlling for sexual IPV, lifetime physical and psychological abuse remained significantly associated with CD4+ activation (P=0.004 and P=0.033, respectively). After controlling for race (the only covariate linked to activation), the lifetime IPV-CD4 activation association remained significant (P=0.012). Alcohol use and depression were identified as potential pathway moderators.

Conclusion: Our data is the first to suggest an immune link between IPV and HIV, and may help explain differences at the individual level in HIV susceptibility and response to biological HIV prevention strategies. The association of psychological and physical abuse with CD4 activation independent of sexual abuse further supports the existence of a stress-induced immune pathway.


Download data is not yet available.

Article Details

Author Biography

Ameeta Shivdas Kalokhe, Emory University School of Medicine, Division of Infectious Diseases; Emory Rollins School of Public Health, Department of Global Health

CD4+ T-cell Activation May Mediate the Effect of Intimate Partner Violence on HIV Susceptibility: a Cross-sectional Study


  1. Breiding MJ, Basile KC, Smith SG, Black MC, Mahendra R. Intimate Partner Violence Surveillance: Uniform Definitions and Recommended Data Elements, Version 2.0.2015. Available from:
  2. Walters ML, Chen J, Breiding MJ. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Findings on Victimization by Sexual Orientation. Atlanta, GA: Centers for Disease Control and Prevention, 2013.
  3. Black MC, Basile KC, Breiding MJ, Smith SG, Walters ML, Merrick MT, Chen J, Stevens MR. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Available from:
  4. Barros C, Schraiber LB, Franca-Junior I. Association between intimate partner violence against women and HIV infection. Rev Saude Publica. 2011;45(2):365-72. PubMed PMID: 21344126.
  5. Maman S, Mbwambo JK, Hogan NM, Kilonzo GP, Campbell JC, Weiss E, Sweat MD. HIV-positive women report more lifetime partner violence: findings from a voluntary counseling and testing clinic in Dar es Salaam, Tanzania. Am J Public Health. 2002;92(8):1331-7. PubMed PMID: 12144993. Pubmed Central PMCID: 1447239.
  6. Jewkes RK, Dunkle K, Nduna M, Shai N. Intimate partner violence, relationship power inequity, and incidence of HIV infection in young women in South Africa: a cohort study. Lancet. 2010;376(9734):41-8. PubMed PMID: 20557928. doi: 10.1016/S0140-6736(10)60548-X
  7. Dunkle KL, Jewkes RK, Brown HC, Gray GE, McIntryre JA, Harlow SD. Gender-based violence, relationship power, and risk of HIV infection in women attending antenatal clinics in South Africa. Lancet. 2004;363(9419):1415-21. PubMed PMID: 15121402. doi: 10.1016/S0140-6736(04)16098-4
  8. Kayibanda JF, Bitera R, Alary M. Violence toward women, men's sexual risk factors, and HIV infection among women: findings from a national household survey in Rwanda. J Acquir Immune Defic Syndr. 2012;59(3):300-7. PubMed PMID: 22227491. doi: 10.1097/QAI.0b013e31823dc634
  9. Shi CF, Kouyoumdjian FG, Dushoff J. Intimate partner violence is associated with HIV infection in women in Kenya: a cross-sectional analysis. BMC Public Health. 2013;13:512. PubMed PMID: 23711189. Pubmed Central PMCID: 3702473. doi: 10.1186/1471-2458-13-512
  10. Silverman JG, Decker MR, Saggurti N, Balaiah D, Raj A. Intimate partner violence and HIV infection among married Indian women. JAMA. 2008;300(6):703-10. PubMed PMID: 18698068. doi: 10.1001/jama.300.6.703
  11. Li Y, Marshall CM, Rees HC, Nunez A, Ezeanolue EE, Ehiri JE. Intimate partner violence and HIV infection among women: a systematic review and meta-analysis. J Int AIDS Soc. 2014;17:18845. PubMed PMID: 24560342. Pubmed Central PMCID: 3925800. doi: 10.7448/IAS.17.1.18845
  12. Kouyoumdjian FG, Calzavara LM, Bondy SJ, O'Campo P, Serwadda D, Nalugoda F, Kagaayi J, Kigozi G, Wawer M, Gray R. Intimate partner violence is associated with incident HIV infection in women in Uganda. AIDS. 2013;27(8):1331-8. PubMed PMID: 23925380. doi: 10.1097/QAD.0b013e32835fd851
  13. Beydoun HA, Beydoun MA, Kaufman JS, Lo B, Zonderman AB. Intimate partner violence against adult women and its association with major depressive disorder, depressive symptoms and postpartum depression: a systematic review and meta-analysis. Social Science & Medicine. 2012;75(6):959-75. PubMed PMID: 22694991. Pubmed Central PMCID: Pmc3537499. doi: 10.1016/j.socscimed.2012.04.025
  14. Coker AL. Does Physical Intimate Partner Violence Affect Sexual Health? Trauma, Violence, & Abuse. 2007;8(2):149-77.
  15. Garcia-Moreno C, Jansen HAFM, Ellsberg M, Heise L, Watts CH. Prevalence of intimate partner violence: findings from the WHO multi-country study on women's health and domestic violence. The Lancet. 2006;368(9543):1260-9.
  16. Campbell JC, Webster D, Koziol-McLain J, Block C, Campbell D, Curry MA, Gary F, Glass N, McFarlane J, Sachs C. Risk factors for femicide in abusive relationships: Results from a multisite case control study. American Journal of Public Health. 2003;93(7).
  17. Breiding MJ, Black MC, Ryan GW. Prevalence and risk factors of intimate partner violence in eighteen US states/territories, 2005. American journal of preventive medicine. 2008;34(2):112-8.
  18. Coker AL, Davis KE, Arias I, Desai S, Sanderson M, Brandt HM, Smith PH. Physical and mental health effects of intimate partner violence for men and women. Am J Prev Med. 2002;23(4):260-8. PubMed PMID: 12406480.
  19. Wu E, El-Bassel N, Witte SS, Gilbert L, Chang M. Intimate partner violence and HIV risk among urban minority women in primary health care settings. AIDS Behav. 2003;7(3):291-301. PubMed PMID: 14586191.
  20. Decker MR, Miller E, McCauley HL, Tancredi DJ, Anderson H, Levenson RR, Silverman JG. Recent partner violence and sexual and drug-related STI/HIV risk among adolescent and young adult women attending family planning clinics. Sex Transm Infect. 2014;90(2):145-9. PubMed PMID: 24234072. Pubmed Central PMCID: 4305329. doi: 10.1136/sextrans-2013-051288
  21. Raj A, Silverman JG, Amaro H. Abused women report greater male partner risk and gender-based risk for HIV: findings from a community-based study with Hispanic women. AIDS Care. 2004;16(4):519-29. PubMed PMID: 15203419. doi: 10.1080/09540120410001683448
  22. Sareen J, Pagura J, Grant B. Is intimate partner violence associated with HIV infection among women in the United States? Gen Hosp Psychiatry. 2009;31(3):274-8. PubMed PMID: 19410107. doi: 10.1016/j.genhosppsych.2009.02.004
  23. Quigley MA, Morgan D, Malamba SS, Mayanja B, Okongo MJ, Carpenter LM, Whitworth JA. Case-control study of risk factors for incident HIV infection in rural Uganda. J Acquir Immune Defic Syndr. 2000;23(5):418-25. PubMed PMID: 10866235.
  24. Li Y, Baker JJ, Korostyshevskiy VR, Slack RS, Plankey MW. The association of intimate partner violence, recreational drug use with HIV seroprevalence among MSM. AIDS Behav. 2012;16(3):491-8. PubMed PMID: 22327371. doi: 10.1007/s10461-012-0157-6
  25. Dillon G, Hussain R, Loxton D, Rahman S. Mental and Physical Health and Intimate Partner Violence against Women: A Review of the Literature. Int J Family Med. 2013;2013:313909. PubMed PMID: 23431441. Pubmed Central PMCID: 3566605. doi: 10.1155/2013/313909
  26. Campbell J, Jones AS, Dienemann J, Kub J, Schollenberger J, O'Campo P, Gielen AC, Wynne C. Intimate partner violence and physical health consequences. Arch Intern Med. 2002;162(10):1157-63. PubMed PMID: 12020187.
  27. Bonomi AE, Anderson ML, Reid RJ, Rivara FP, Carrell D, Thompson RS. Medical and psychosocial diagnoses in women with a history of intimate partner violence. Arch Intern Med. 2009;169(18):1692-7. PubMed PMID: 19822826. doi: 10.1001/archinternmed.2009.292
  28. Garcia-Linares MI, Sanchez-Lorente S, Coe CL, Martinez M. Intimate male partner violence impairs immune control over herpes simplex virus type 1 in physically and psychologically abused women. Psychosom Med. 2004;66(6):965-72. PubMed PMID: 15564366. doi: 10.1097/01.psy.0000145820.90041.c0
  29. Sanchez-Lorente S, Blasco-Ros C, Coe CL, Martinez M. Recovery of immune control over herpes simplex virus type 1 in female victims of intimate partner violence. Psychosom Med. 2010;72(1):97-106. PubMed PMID: 19933506. doi: 10.1097/PSY.0b013e3181c5080a
  30. Constantino RE, Sekula LK, Rabin B, Stone C. Negative life experiences, depression, and immune function in abused and nonabused women. Biol Res Nurs. 2000;1(3):190-8. PubMed PMID: 11232214.
  31. Woods SJ, Wineman NM, Page GG, Hall RJ, Alexander TS, Campbell JC. Predicting immune status in women from PTSD and childhood and adult violence. ANS Adv Nurs Sci. 2005;28(4):306-19. PubMed PMID: 16292017.
  32. Jewkes R, Dunkle K, Jama-Shai N, Gray G. Impact of exposure to intimate partner violence on CD4+ and CD8+ T cell decay in HIV infected women: longitudinal study. PLoS One. 2015;10(3):e0122001. PubMed PMID: 25816336. Pubmed Central PMCID: 4376679. doi: 10.1371/journal.pone.0122001
  33. Steiner K, Myrie L, Malhotra I, Mungai P, Muchiri E, Dent A, King CL. Fetal immune activation to malaria antigens enhances susceptibility to in vitro HIV infection in cord blood mononuclear cells. J Infect Dis. 2010;202(6):899-907. PubMed PMID: 20687848. Pubmed Central PMCID: 3620023. doi: 10.1086/655783
  34. Pancino G, Saez-Cirion A, Scott-Algara D, Paul P. Natural resistance to HIV infection: lessons learned from HIV-exposed uninfected individuals. J Infect Dis. 2010;202 Suppl 3:S345-50. PubMed PMID: 20887222. doi: 10.1086/655973
  35. McLaren PJ, Ball TB, Wachihi C, Jaoko W, Kelvin DJ, Danesh A, Kimani J, Plummer FA, Fowke KR. HIV-exposed seronegative commercial sex workers show a quiescent phenotype in the CD4+ T cell compartment and reduced expression of HIV-dependent host factors. J Infect Dis. 2010;202 Suppl 3:S339-44. PubMed PMID: 20887221. doi: 10.1086/655968
  36. Card CM, McLaren PJ, Wachihi C, Kimani J, Plummer FA, Fowke KR. Decreased immune activation in resistance to HIV-1 infection is associated with an elevated frequency of CD4(+)CD25(+)FOXP3(+) regulatory T cells. J Infect Dis. 2009;199(9):1318-22. PubMed PMID: 19301980. doi: 10.1086/597801
  37. Begaud E, Chartier L, Marechal V, Ipero J, Leal J, Versmisse P, Breton G, Fontanet A, Capoulade-Metay C, Fleury H, Barre-Sinoussi F, Scott-Algara D, Pancino G. Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in exposed uninfected Central Africans. Retrovirology. 2006;3:35. PubMed PMID: 16792805. Pubmed Central PMCID: 1524799. doi: 10.1186/1742-4690-3-35
  38. Zhang Z, Schuler T, Zupancic M, Wietgrefe S, Staskus KA, Reimann KA, Reinhart TA, Rogan M, Cavert W, Miller CJ, Veazey RS, Notermans D, Little S, Danner SA, Richman DD, Havlir D, Wong J, Jordan HL, Schacker TW, Racz P, Tenner-Racz K, Letvin NL, Wolinsky S, Haase AT. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science. 1999;286(5443):1353-7. PubMed PMID: 10558989.
  39. Zhang ZQ, Wietgrefe SW, Li Q, Shore MD, Duan L, Reilly C, Lifson JD, Haase AT. Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 2004;101(15):5640-5. PubMed PMID: 15064398. Pubmed Central PMCID: 397458. doi: 10.1073/pnas.0308425101
  40. Legrand FA, Nixon DF, Loo CP, Ono E, Chapman JM, Miyamoto M, Diaz RS, Santos AM, Succi RC, Abadi J, Rosenberg MG, de Moraes-Pinto MI, Kallas EG. Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal. PLoS One. 2006;1:e102. PubMed PMID: 17183635. Pubmed Central PMCID: 1762312. doi: 10.1371/journal.pone.0000102
  41. Card CM, Rutherford WJ, Ramdahin S, Yao X, Kimani M, Wachihi C, Kimani J, Plummer FA, Ball TB, Fowke KR. Reduced cellular susceptibility to in vitro HIV infection is associated with CD4+ T cell quiescence. PLoS One. 2012;7(9):e45911. PubMed PMID: 23029309. Pubmed Central PMCID: 3448692. doi: 10.1371/journal.pone.0045911
  42. World Health Organization. Putting Women First: Ethical and Safety Recommendations for Research on Domestic Violence Against Women 2001. Available from:
  43. Thompson MP, Basile KC, Hertz MF, Sitterle D. Measuring Intimate Partner Violence Victimization and Perpetration: A compendium of Assessment Tools 2006.
  44. Williams DR, Yan Y, Jackson JS, Anderson NB. Racial Differences in Physical and Mental Health: Socio-economic Status, Stress and Discrimination. J Health Psychol. 1997;2(3):335-51. PubMed PMID: 22013026. doi: 10.1177/135910539700200305
  45. Foa EB, Riggs DS, Dancu CV, Rothbaum BO. Reliability and Validity of a Brief Instrument for Assessing Post-traumatic Stress Disorder. J Traumatic Stress. 1993;6(4):459-73.
  46. Zhang W, O'Brien N, Forrest JI, Salters KA, Patterson TL, Montaner JS, Hogg RS, Lima VD. Validating a shortened depression scale (10 item CES-D) among HIV-positive people in British Columbia, Canada. PLoS One. 2012;7(7):e40793. PubMed PMID: 22829885. Pubmed Central PMCID: 3400644. doi: 10.1371/journal.pone.0040793
  47. Ibegbu CC, Xu YX, Fillos D, Radziewicz H, Grakoui A, Kourtis AP. Differential expression of CD26 on virus-specific CD8(+) T cells during active, latent and resolved infection. Immunology. 2009;126(3):346-53. PubMed PMID: 18657205. Pubmed Central PMCID: 2669815. doi: 10.1111/j.1365-2567.2008.02899.x
  48. Pan X, Baldauf HM, Keppler OT, Fackler OT. Restrictions to HIV-1 replication in resting CD4+ T lymphocytes. Cell Res. 2013;23(7):876-85. PubMed PMID: 23732522. Pubmed Central PMCID: 3698640. doi: 10.1038/cr.2013.74
  49. Dekaris D, Sabioncello A, Mazuran R, Rabatic S, Svoboda-Beusan I, Racunica NL, Tomasic J. Multiple changes of immunologic parameters in prisoners of war. Assessments after release from a camp in Manjaca, Bosnia. JAMA. 1993;270(5):595-9. PubMed PMID: 8331758.
  50. Wilson SN, van der Kolk B, Burbridge J, Fisler R, Kradin R. Phenotype of blood lymphocytes in PTSD suggests chronic immune activation. Psychosomatics. 1999;40(3):222-5. PubMed PMID: 10341534. doi: 10.1016/S0033-3182(99)71238-7
  51. Lemieux A, Coe CL, Carnes M. Symptom severity predicts degree of T cell activation in adult women following childhood maltreatment. Brain Behav Immun. 2008;22(6):994-1003. PubMed PMID: 18396007. Pubmed Central PMCID: 2532919. doi: 10.1016/j.bbi.2008.02.005
  52. Bielas H, Jud A, Lips U, Reichenbach J, Landolt MA. Increased number of activated T cells in lymphocyte subsets of maltreated children: data from a pilot study. J Psychosom Res. 2012;73(4):313-8. PubMed PMID: 22980539. doi: 10.1016/j.jpsychores.2012.08.003
  53. Maes M, Stevens WJ, Declerck LS, Bridts CH, Peeters D, Schotte C, Cosyns P. Significantly increased expression of T-cell activation markers (interleukin-2 and HLA-DR) in depression: further evidence for an inflammatory process during that illness. Prog Neuropsychopharmacol Biol Psychiatry. 1993;17(2):241-55. PubMed PMID: 8430217.
  54. Buske-Kirschbaum A, Kern S, Ebrecht M, Hellhammer DH. Altered distribution of leukocyte subsets and cytokine production in response to acute psychosocial stress in patients with psoriasis vulgaris. Brain Behav Immun. 2007;21(1):92-9. PubMed PMID: 16714097. doi: 10.1016/j.bbi.2006.03.006
  55. Berard M, Tough DF. Qualitative differences between naive and memory T cells. Immunology. 2002;106(2):127-38. PubMed PMID: 12047742. Pubmed Central PMCID: 1782715.
  56. Croft M. Activation of naive, memory and effector T cells. Curr Opin Immunol. 1994;6(3):431-7. PubMed PMID: 7917111.
  57. Blanco J, Barretina J, Gutierrez A, Armand-Ugon M, Cabrera C, Clotet B, Este JA. Preferential attachment of HIV particles to activated and CD45RO+CD4+ T cells. AIDS Res Hum Retroviruses. 2002;18(1):27-38. PubMed PMID: 11804554. doi: 10.1089/088922202753394691
  58. Dai J, Agosto LM, Baytop C, Yu JJ, Pace MJ, Liszewski MK, O'Doherty U. Human immunodeficiency virus integrates directly into naive resting CD4+ T cells but enters naive cells less efficiently than memory cells. J Virol. 2009;83(9):4528-37. PubMed PMID: 19211752. Pubmed Central PMCID: 2668451. doi: 10.1128/JVI.01910-08
  59. Koning FA, Otto SA, Hazenberg MD, Dekker L, Prins M, Miedema F, Schuitemaker H. Low-level CD4+ T cell activation is associated with low susceptibility to HIV-1 infection. J Immunol. 2005;175(9):6117-22. PubMed PMID: 16237108.
  60. Schnittman SM, Lane HC, Greenhouse J, Justement JS, Baseler M, Fauci AS. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc Natl Acad Sci U S A. 1990;87(16):6058-62. PubMed PMID: 2385584. Pubmed Central PMCID: 54471.
  61. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10(7):490-500. PubMed PMID: 20559327. doi: 10.1038/nri2785
  62. Baecher-Allan C, Wolf E, Hafler DA. MHC class II expression identifies functionally distinct human regulatory T cells. J Immunol. 2006;176(8):4622-31. PubMed PMID: 16585553.
  63. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, Parizot C, Taflin C, Heike T, Valeyre D, Mathian A, Nakahata T, Yamaguchi T, Nomura T, Ono M, Amoura Z, Gorochov G, Sakaguchi S. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30(6):899-911. PubMed PMID: 19464196. doi: 10.1016/j.immuni.2009.03.019
  64. Simonetta F, Bourgeois C. CD4+FOXP3+ Regulatory T-Cell Subsets in Human Immunodeficiency Virus Infection. Front Immunol. 2013;4:215. PubMed PMID: 23908654. Pubmed Central PMCID: 3727053. doi: 10.3389/fimmu.2013.00215