Skip to main content

Advertisement

Log in

Sexual dimorphism in HIV-1 infection

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Sex-specific differences affecting various aspects of HIV-1 infection have been reported, including differences in susceptibility to infection, course of HIV-1 disease, and establishment of viral reservoirs. Once infected, initial plasma levels of HIV-1 viremia in women are lower compared to men while the rates of progression to AIDS are similar. Factors contributing to these sex differences are poorly understood, and range from anatomical differences and differential expression of sex hormones to differences in immune responses, the microbiome and socio-economic discrepancies, all of which may impact HIV-1 acquisition and disease progression. Ongoing research efforts aiming at controlling HIV-1 disease or reducing viral reservoirs need to take these sex-based differences in HIV-1 pathogenesis into account. In this review, we discuss established knowledge and recent findings on immune pathways leading to sex differences in HIV-1 disease manifestations, with focus on HIV-1 latency and the effect of female sex hormones on HIV-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Delmas MC, Jadand C, de Vincenzi I, Deveau C, Persoz A, Sobel A, Kazatchkine M, Brunet JB, Meyer L (1997) Gender difference in CD4+ cell counts persist after HIV-1 infection. SEROCO Study Group. AIDS 11(8):1071–1073

    CAS  PubMed  Google Scholar 

  2. Prins M, Robertson JR, Brettle RP, Aguado IH, Broers B, Boufassa F, Goldberg DJ, Zangerle R, Coutinho RA, van den Hoek A (1999) Do gender differences in CD4 cell counts matter? AIDS 13(17):2361–2364

    Article  CAS  PubMed  Google Scholar 

  3. Meditz, A.L., MaWhinney S., Allshouse A., Feser W., Markowitz M., Little S., Hecht R., Daar E.S., Collier A.C., Margolick J., Kilby J.M., Routy J.P., Conway B., Kaldor J., Levy J., Schooley R., Cooper D.A., Altfeld M., Richman D., Connick E., Sex, race, and geographic region influence clinical outcomes following primary HIV-1 infection. J Infect Dis, 2011. 203(4): p. 442–51

  4. Grabar, S., Selinger-Leneman H., Abgrall S., Pialoux G., Weiss L., Costagliola D., Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS, 2009. 23(9): p. 1163–9

  5. Saez-Cirion A, Hamimi C, Bergamaschi A, David A, Versmisse P, Melard A, Boufassa F, Barre-Sinoussi F, Lambotte O, Rouzioux C, Pancino G, for the ANRS CO18 Cohort (2011) Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers. Blood 118(4):955–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB, Quinn TC (2001) Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. N Engl J Med 344(10):720–725

    Article  CAS  PubMed  Google Scholar 

  7. Farzadegan H, Hoover DR, Astemborski J, Lyles CM, Margolick JB, Markham RB, Quinn TC, Vlahov D (1998) Sex differences in HIV-1 viral load and progression to AIDS. Lancet 352(9139):1510–1514

    Article  CAS  PubMed  Google Scholar 

  8. Santelli JS, Speizer IS, Edelstein ZR (2013) Abstinence promotion under PEPFAR: the shifting focus of HIV prevention for youth. Glob Public Health 8(1):1–12

    Article  PubMed  PubMed Central  Google Scholar 

  9. Griesbeck M, Scully E, Altfeld M (2016) Sex and gender differences in HIV-1 infection. Clin Sci (Lond) 130(16):1435–1451

    Article  CAS  Google Scholar 

  10. Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee TH, Robles YP, Davis BT, Li JZ, Heisey A, Hill AL, Busch MP, Armand P, Soiffer RJ, Altfeld M, Kuritzkes DR (2014) Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med 161(5):319–327

    Article  PubMed  PubMed Central  Google Scholar 

  11. Giacomet V, Trabattoni D, Zanchetta N, Biasin M, Gismondo M, Clerici M, Zuccotti G (2014) No cure of HIV infection in a child despite early treatment and apparent viral clearance. Lancet 384(9950):1320

    Article  PubMed  Google Scholar 

  12. International, A.S.S.W.G.o.H.I.V.C et al (2012) Towards an HIV cure: a global scientific strategy. Nat Rev Immunol 12(8):607–614

    Article  CAS  Google Scholar 

  13. Chun TW, Nickle DC, Justement JS, Meyers JH, Roby G, Hallahan CW, Kottilil S, Moir S, Mican JAM, Mullins JI, Ward DJ, Kovacs JA, Mannon PJ, Fauci AS (2008) Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 197(5):714–720

    Article  CAS  PubMed  Google Scholar 

  14. Yukl SA, Gianella S, Sinclair E, Epling L, Li Q, Duan L, Choi ALM, Girling V, Ho T, Li P, Fujimoto K, Lampiris H, Hare CB, Pandori M, Haase AT, Günthard HF, Fischer M, Shergill AK, McQuaid K, Havlir DV, Wong JK (2010) Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis 202(10):1553–1561

    Article  PubMed  Google Scholar 

  15. Poles MA, Boscardin WJ, Elliott J, Taing P, Fuerst MMP, McGowan I, Brown S, Anton PA (2006) Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals. J Acquir Immune Defic Syndr 43(1):65–68

    Article  PubMed  Google Scholar 

  16. d'Ettorre G, Paiardini M, Zaffiri L, Andreotti M, Ceccarelli G, Rizza C, Indinnimeo M, Vella S, M. Mastroianni C, Silvestri G, Vullo V (2011) HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS. Curr HIV Res 9(3):148–153

    Article  CAS  PubMed  Google Scholar 

  17. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Siliciano RF (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387(6629):183–188

    Article  CAS  PubMed  Google Scholar 

  18. Yerly S, Perneger TV, Vora S, Hirschel B, Perrin L (2000) Decay of cell-associated HIV-1 DNA correlates with residual replication in patients treated during acute HIV-1 infection. AIDS 14(18):2805–2812

    Article  CAS  PubMed  Google Scholar 

  19. Haase AT (1999) Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annu Rev Immunol 17:625–656

    Article  CAS  PubMed  Google Scholar 

  20. Wong JK, Gunthard HF, Havlir DV, Zhang ZQ, Haase AT, Ignacio CC, Kwok S, Emini E, Richman DD (1997) Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure. Proc Natl Acad Sci U S A 94(23):12574–12579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Banga R, Procopio FA, Noto A, Pollakis G, Cavassini M, Ohmiti K, Corpataux JM, de Leval L, Pantaleo G, Perreau M (2016) PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med 22(7):754–761

    Article  CAS  PubMed  Google Scholar 

  22. Perreau M, Savoye AL, de Crignis E, Corpataux JM, Cubas R, Haddad EK, de Leval L, Graziosi C, Pantaleo G (2013) Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med 210(1):143–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Couturier J, Suliburk JW, Brown JM, Luke DJ, Agarwal N, Yu X, Nguyen C, Iyer D, Kozinetz CA, Overbeek PA, Metzker ML, Balasubramanyam A, Lewis DE (2015) Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS 29(6):667–674

    Article  CAS  PubMed  Google Scholar 

  24. Davis KE, D. Neinast M, Sun K, M. Skiles W, D. Bills J, A. Zehr J, Zeve D, D. Hahner L, W. Cox D, M. Gent L, Xu Y, V. Wang Z, A. Khan S, Clegg DJ (2013) The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Mol Metab 2(3):227–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Karastergiou K, Smith SR, Greenberg AS, Fried SK (2012) Sex differences in human adipose tissues - the biology of pear shape. Biol Sex Differ 3(1):13

    Article  PubMed  PubMed Central  Google Scholar 

  26. Beasley LE, Koster A, Newman AB, Javaid MK, Ferrucci L, Kritchevsky SB, Kuller LH, Pahor M, Schaap LA, Visser M, Rubin SM, Goodpaster BH, Harris TB, The Health ABC study (2009) Inflammation and race and gender differences in computerized tomography-measured adipose depots. Obesity (Silver Spring) 17(5):1062–1069

    Article  Google Scholar 

  27. Zore T, Palafox M, Reue K (2018) Sex differences in obesity, lipid metabolism, and inflammation-a role for the sex chromosomes? Mol Metab 15:35–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kramer-Hammerle S et al (2005) Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 111(2):194–213

    Article  CAS  PubMed  Google Scholar 

  29. Marban C et al (2016) Targeting the brain reservoirs: toward an HIV cure. Front Immunol 7:397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Churchill MJ et al (2006) Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J Neuro-Oncol 12(2):146–152

    Google Scholar 

  31. Thompson KA, Cherry CL, Bell JE, McLean CA (2011) Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals. Am J Pathol 179(4):1623–1629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nickle DC, Jensen MA, Shriner D, Brodie SJ, Frenkel LM, Mittler JE, Mullins JI (2003) Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments. J Virol 77(9):5540–5546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cory TJ, Schacker TW, Stevenson M, Fletcher CV (2013) Overcoming pharmacologic sanctuaries. Curr Opin HIV AIDS 8(3):190–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Joseph SB et al (2015) HIV-1 target cells in the CNS. J Neuro-Oncol 21(3):276–289

    CAS  Google Scholar 

  35. Arrildt KT, Joseph SB, Swanstrom R (2012) The HIV-1 env protein: a coat of many colors. Curr HIV/AIDS Rep 9(1):52–63

    Article  PubMed  PubMed Central  Google Scholar 

  36. Witt KA, Sandoval KE (2014) Steroids and the blood-brain barrier: therapeutic implications. Adv Pharmacol 71:361–390

    Article  CAS  PubMed  Google Scholar 

  37. Cuzin L, Pugliese P, Sauné K, Allavena C, Ghosn J, Cottalorda J, Rodallec A, Chaix ML, Fafi-Kremer S, Soulié C, Ouka M, Charpentier C, Bocket L, Mirand A, Guiguet M, Dat’AIDS study group (2015) Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy. AIDS 29(13):1665–1671

    Article  CAS  PubMed  Google Scholar 

  38. Macedo, A.B., Resop R.S., Martins L.J., Szaniawski M.A., Sorensen E.S., Spivak A.M., Nixon D.F., Jones R.B., Planelles V., Bosque A., Influence of biological sex, age and HIV status in an in vitro primary cell model of HIV latency using a CXCR4 tropic virus. AIDS Res Hum Retrovir, 2018

  39. Johnston RE, Heitzeg MM (2015) Sex, age, race and intervention type in clinical studies of HIV cure: a systematic review. AIDS Res Hum Retrovir 31(1):85–97

    Article  PubMed  PubMed Central  Google Scholar 

  40. Fourati S, Flandre P, Calin R, Carcelain G, Soulie C, Lambert-Niclot S, Maiga A, Ait-Arkoub Z, Tubiana R, Valantin MA, Autran B, Katlama C, Calvez V, Marcelin AG (2014) Factors associated with a low HIV reservoir in patients with prolonged suppressive antiretroviral therapy. J Antimicrob Chemother 69(3):753–756

    Article  CAS  PubMed  Google Scholar 

  41. Ngo-Giang-Huong N, Deveau C, da Silva I, Pellegrin I, Venet A, Harzic M, Sinet M, Delfraissy JF, Meyer L, Goujard C, Rouzioux C, Frnech PRIMO Cohort Study Group (2001) Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy. AIDS 15(6):665–673

    Article  CAS  PubMed  Google Scholar 

  42. Ghosn J, Deveau C, Chaix ML, Goujard C, Galimand J, Zitoun Y, Allegre T, Delfraissy JF, Meyer L, Rouzioux C, on behalf of the ANRS PRIMO Cohort (2010) Despite being highly diverse, immunovirological status strongly correlates with clinical symptoms during primary HIV-1 infection: a cross-sectional study based on 674 patients enrolled in the ANRS CO 06 PRIMO cohort. J Antimicrob Chemother 65(4):741–748

    Article  CAS  PubMed  Google Scholar 

  43. Mocroft A, Gill MJ, Davidson W, Phillips AN (2000) Are there gender differences in starting protease inhibitors, HAART, and disease progression despite equal access to care? J Acquir Immune Defic Syndr 24(5):475–482

    Article  CAS  PubMed  Google Scholar 

  44. Stein MD, Crystal S, Cunningham WE, Ananthanarayanan A, Andersen RM, Turner BJ, Zierler S, Morton S, Katz MH, Bozzette SA, Shapiro MF, Schuster MA (2000) Delays in seeking HIV care due to competing caregiver responsibilities. Am J Public Health 90(7):1138–1140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stein MD, Leibman B, Wachtel TJ, Carpenter CCJ, Fisher A, Durand L, O’Sullivan PS, Mayer KH (1991) HIV-positive women: reasons they are tested for HIV and their clinical characteristics on entry into the health care system. J Gen Intern Med 6(4):286–289

    Article  CAS  PubMed  Google Scholar 

  46. Cohen MH, Cook JA, Grey D, Young M, Hanau LH, Tien P, Levine AM, Wilson TE (2004) Medically eligible women who do not use HAART: the importance of abuse, drug use, and race. Am J Public Health 94(7):1147–1151

    Article  PubMed  PubMed Central  Google Scholar 

  47. Das B, Dobrowolski C, Luttge B, Valadkhan S, Chomont N, Johnston R, Bacchetti P, Hoh R, Gandhi M, Deeks SG, Scully E, Karn J (2018) Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir. Proc Natl Acad Sci U S A 115:E7795–E7804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Moore MD, Hu WS (2009) HIV-1 RNA dimerization: it takes two to tango. AIDS Rev 11(2):91–102

    PubMed  PubMed Central  Google Scholar 

  49. Fitzgerald-Bocarsly P, Dai J, Singh S (2008) Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. Cytokine Growth Factor Rev 19(1):3–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Katze MG, He Y, Gale M Jr (2002) Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2(9):675–687

    Article  CAS  PubMed  Google Scholar 

  51. Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK, Kulkarni S, Wen TF, Lindsay RJ, Orellana L, Mildvan D, Bazner S, Streeck H, Alter G, Lifson JD, Carrington M, Bosch RJ, Robbins GK, Altfeld M (2009) Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med 15(8):955–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chang JJ, Woods M, Lindsay RJ, Doyle EH, Griesbeck M, Chan ES, Robbins GK, Bosch RJ, Altfeld M (2013) Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication. J Infect Dis 208(5):830–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Seillet C, Laffont S, Tremollieres F, Rouquie N, Ribot C, Arnal JF, Douin-Echinard V, Gourdy P, Guery JC (2012) The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. Blood 119(2):454–464

    Article  CAS  PubMed  Google Scholar 

  54. Ziegler SM, Beisel C, Sutter K, Griesbeck M, Hildebrandt H, Hagen SH, Dittmer U, Altfeld M (2017) Human pDCs display sex-specific differences in type I interferon subtypes and interferon alpha/beta receptor expression. Eur J Immunol 47(2):251–256

    Article  CAS  PubMed  Google Scholar 

  55. Griesbeck M, Ziegler S, Laffont S, Smith N, Chauveau L, Tomezsko P, Sharei A, Kourjian G, Porichis F, Hart M, Palmer CD, Sirignano M, Beisel C, Hildebrandt H, Cenac C, Villani AC, Diefenbach TJ, le Gall S, Schwartz O, Herbeuval JP, Autran B, Guery JC, Chang JJ, Altfeld M (2015) Sex differences in plasmacytoid dendritic cell levels of IRF5 drive higher IFN-alpha production in women. J Immunol 195(11):5327–5336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Berghofer B, Frommer T, Haley G, Fink L, Bein G, Hackstein H (2006) TLR7 ligands induce higher IFN-alpha production in females. J Immunol 177(4):2088–2096

    Article  PubMed  Google Scholar 

  57. Carrel L, Cottle AA, Goglin KC, Willard HF (1999) A first-generation X-inactivation profile of the human X chromosome. Proc Natl Acad Sci U S A 96(25):14440–14444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Balaton BP, Dixon-McDougall T, Peeters SB, Brown CJ (2018) The eXceptional nature of the X chromosome. In: Hum Mol Genet, vol 27, pp R242–R249

    Google Scholar 

  59. Peeters SB, Korecki AJ, Simpson EM, Brown CJ (2018) Human cis-acting elements regulating escape from X-chromosome inactivation function in mouse. Hum Mol Genet 27(7):1252–1262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Laffont S, Rouquié N, Azar P, Seillet C, Plumas J, Aspord C, Guéry JC (2014) X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women. J Immunol 193(11):5444–5452

    Article  CAS  PubMed  Google Scholar 

  61. Tsai A, Irrinki A, Kaur J, Cihlar T, Kukolj G, Sloan DD, Murry JP (2017) Toll-like receptor 7 agonist GS-9620 induces HIV expression and HIV-specific immunity in cells from HIV-infected individuals on suppressive antiretroviral therapy. J Virol 91(8)

  62. Bam RA, Hansen D, Irrinki A, Mulato A, Jones GS, Hesselgesser J, Frey CR, Cihlar T, Yant SR (2017) TLR7 agonist GS-9620 is a potent inhibitor of acute HIV-1 infection in human peripheral blood mononuclear cells. Antimicrob Agents Chemother 61(1)

  63. Cutolo M, Sulli A, Straub RH (2014) Estrogen’s effects in chronic autoimmune/inflammatory diseases and progression to cancer. Expert Rev Clin Immunol 10(1):31–39

    Article  CAS  PubMed  Google Scholar 

  64. Klein SL, Marriott I, Fish EN (2015) Sex-based differences in immune function and responses to vaccination. Trans R Soc Trop Med Hyg 109(1):9–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hagen S, Altfeld M (2016) The X awakens: multifactorial ramifications of sex-specific differences in HIV-1 infection. J Virus Erad 2(2):78–81

    PubMed  PubMed Central  Google Scholar 

  66. Fish EN (2008) The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 8(9):737–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Arruvito L, Sanz M, Banham AH, Fainboim L (2007) Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol 178(4):2572–2578

    Article  CAS  PubMed  Google Scholar 

  68. Mingjia, L. and R. Short, How oestrogen or progesterone might change a woman’s susceptibility to HIV-1 infection. Aust N Z J Obstet Gynaecol, 2002. 42(5): p. 472–5

  69. Kaushic C, Roth KL, Anipindi V, Xiu F (2011) Increased prevalence of sexually transmitted viral infections in women: the role of female sex hormones in regulating susceptibility and immune responses. J Reprod Immunol 88(2):204–209

    Article  CAS  PubMed  Google Scholar 

  70. Tan IJ, Peeva E, Zandman-Goddard G (2015) Hormonal modulation of the immune system - a spotlight on the role of progestogens. Autoimmun Rev 14(6):536–542

    Article  CAS  PubMed  Google Scholar 

  71. Polis CB, Curtis KM (2013) Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis 13(9):797–808

    Article  PubMed  Google Scholar 

  72. Byrne EH, Anahtar MN, Cohen KE, Moodley A, Padavattan N, Ismail N, Bowman BA, Olson GS, Mabhula A, Leslie A, Ndung'u T, Walker BD, Ghebremichael MS, Dong KL, Kwon DS (2016) Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in south African women: a prospective cohort study. Lancet Infect Dis 16(4):441–448

    Article  CAS  PubMed  Google Scholar 

  73. Dominguez F, Galan A, Martin JJ, Remohi J, Pellicer A, Simón C (2003) Hormonal and embryonic regulation of chemokine receptors CXCR1, CXCR4, CCR5 and CCR2B in the human endometrium and the human blastocyst. Mol Hum Reprod 9(4):189–198

    Article  CAS  PubMed  Google Scholar 

  74. Prakash M, Kapembwa MS, Gotch F, Patterson S (2002) Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women. J Reprod Immunol 54(1–2):117–131

    Article  CAS  PubMed  Google Scholar 

  75. Sheffield JS, Wendel GD Jr, McIntire DD, Norgard MV (2009) The effect of progesterone levels and pregnancy on HIV-1 coreceptor expression. Reprod Sci 16(1):20–31

    Article  CAS  PubMed  Google Scholar 

  76. Vassiliadou N, Tucker L, Anderson DJ (1999) Progesterone-induced inhibition of chemokine receptor expression on peripheral blood mononuclear cells correlates with reduced HIV-1 infectability in vitro. J Immunol 162(12):7510–7518

    CAS  PubMed  Google Scholar 

  77. Thomson KA, Hughes J, Baeten JM, John-Stewart G, Celum C, Cohen CR, Ngure K, Kiarie J, Mugo N, Heffron R, Partners in Prevention HSV/HIV Transmission Study and Partners PrEP Study Teams (2018) Increased risk of HIV acquisition among women throughout pregnancy and during the postpartum period: a prospective per-coital-act analysis among women with HIV-infected partners. J Infect Dis 218(1):16–25

    Article  PubMed  PubMed Central  Google Scholar 

  78. Money DM, Arikan YY, Remple V, Sherlock C, Craib K, Birch P, Burdge DR (2003) Genital tract and plasma human immunodeficiency virus viral load throughout the menstrual cycle in women who are infected with ovulatory human immunodeficiency virus. Am J Obstet Gynecol 188(1):122–128

    Article  PubMed  Google Scholar 

  79. Reichelderfer PS, Coombs RW, Wright DJ, Cohn J, Burns DN, Cu-Uvin S, Baron PA, Cohen MH, Landay AL, Beckner SK, Lewis SR, Kovacs AA (2000) Effect of menstrual cycle on HIV-1 levels in the peripheral blood and genital tract. WHS 001 Study Team. AIDS 14(14):2101–2107

    Article  CAS  PubMed  Google Scholar 

  80. Greenblatt RM, Ameli N, Grant RM, Bacchetti P, Taylor RN (2000) Impact of the ovulatory cycle on virologic and immunologic markers in HIV-infected women. J Infect Dis 181(1):82–90

    Article  CAS  PubMed  Google Scholar 

  81. Laffont S, Seillet C, Guery JC (2017) Estrogen receptor-dependent regulation of dendritic cell development and function. Front Immunol 8:108

    PubMed  PubMed Central  Google Scholar 

  82. Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N, Pitha PM, Fitzgerald KA, Golenbock DT (2005) The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. J Biol Chem 280(17):17005–17012

    Article  CAS  PubMed  Google Scholar 

  83. Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano SI, Honda K, Ohba Y, Mak TW, Taniguchi T (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434(7030):243–249

    Article  CAS  PubMed  Google Scholar 

  84. Aral SO, Fenton KA, Holmes KK (2007) Sexually transmitted diseases in the USA: temporal trends. Sex Transm Infect 83(4):257–266

    Article  PubMed  PubMed Central  Google Scholar 

  85. Haro C et al (2016) Intestinal microbiota is influenced by gender and body mass index. PLoS One 11(5):e0154090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dominianni C, Sinha R, Goedert JJ, Pei Z, Yang L, Hayes RB, Ahn J (2015) Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PLoS One 10(4):e0124599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Huang B, Fettweis JM, Brooks JP, Jefferson KK, Buck GA (2014) The changing landscape of the vaginal microbiome. Clin Lab Med 34(4):747–761

    Article  PubMed  PubMed Central  Google Scholar 

  88. McClelland RS, Lingappa JR, Srinivasan S, Kinuthia J, John-Stewart GC, Jaoko W, Richardson BA, Yuhas K, Fiedler TL, Mandaliya KN, Munch MM, Mugo NR, Cohen CR, Baeten JM, Celum C, Overbaugh J, Fredricks DN (2018) Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study. Lancet Infect Dis 18(5):554–564

    Article  PubMed  PubMed Central  Google Scholar 

  89. Passmore JS, Jaspan HB (2018) Vaginal microbes, inflammation, and HIV risk in African women. Lancet Infect Dis 18(5):483–484

    Article  PubMed  Google Scholar 

  90. Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, Abou M, Westmacott GR, McCorrister S, Kwatampora J, Nyanga B, Kimani J, Masson L, Liebenberg LJ, Abdool Karim SS, Passmore JAS, Lauffenburger DA, Kaul R, McKinnon LR (2016) Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol 9(1):194–205

    Article  CAS  PubMed  Google Scholar 

  91. McKinnon LR, Liebenberg LJ, Yende-Zuma N, Archary D, Ngcapu S, Sivro A, Nagelkerke N, Garcia Lerma JG, Kashuba AD, Masson L, Mansoor LE, Karim QA, Karim SSA, Passmore JAS (2018) Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women. Nat Med 24(4):491–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Klatt NR, Cheu R, Birse K, Zevin AS, Perner M, Noël-Romas L, Grobler A, Westmacott G, Xie IY, Butler J, Mansoor L, McKinnon LR, Passmore JAS, Abdool Karim Q, Abdool Karim SS, Burgener AD (2017) Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science 356(6341):938–945

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marcus Altfeld.

Additional information

This article is a contribution to the special issue on Sex differences in immunity – Guest Editors: Hanna Lotter and Marcus Altfeld

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rechtien, A., Altfeld, M. Sexual dimorphism in HIV-1 infection. Semin Immunopathol 41, 195–202 (2019). https://doi.org/10.1007/s00281-018-0704-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-018-0704-y

Keywords

Navigation