Brief Report: Herpes Simplex Virus Type-2 Shedding and Genital Ulcers During Early HIV in Zimbabwean Women.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
28
10
2020
accepted:
25
01
2021
pubmed:
16
2
2021
medline:
7
10
2021
entrez:
15
2
2021
Statut:
ppublish
Résumé
Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, viral DNA shedding and/or ulcers) preceded HIV acquisition in the hormonal contraception and HIV cohort. Zimbabwean women who acquired HIV were matched to HIV-negative women on visit, age, and bacterial sexually transmitted infections. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction tested for viral shedding. Self-reported and clinician-diagnosed ulcers were documented. Multivariable logistic regression, accounting for matching, estimated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) at each visit. Of 387 HSV-2 seropositive women, most had prevalent as compared with incident HSV-2 (91% vs. 9%, respectively). HSV-2 viral shedding was more common among HIV seroconverters than HIV-negative women (26% vs. 14%, P < 0.01). Shedding occurred around HIV acquisition (t-3months aOR, 2.7; 95% CI, 0.8 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 6.6). Genital ulcers were reported more often among HIV seroconverters than HIV-negative women (13% vs. 7%; P = 0.06) and detection was after HIV acquisition (t+6months aOR, 14.5; 95% CI, 1.6 to 133.9). HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.
Sections du résumé
BACKGROUND
Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, viral DNA shedding and/or ulcers) preceded HIV acquisition in the hormonal contraception and HIV cohort.
METHODS
Zimbabwean women who acquired HIV were matched to HIV-negative women on visit, age, and bacterial sexually transmitted infections. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction tested for viral shedding. Self-reported and clinician-diagnosed ulcers were documented. Multivariable logistic regression, accounting for matching, estimated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) at each visit.
RESULTS
Of 387 HSV-2 seropositive women, most had prevalent as compared with incident HSV-2 (91% vs. 9%, respectively). HSV-2 viral shedding was more common among HIV seroconverters than HIV-negative women (26% vs. 14%, P < 0.01). Shedding occurred around HIV acquisition (t-3months aOR, 2.7; 95% CI, 0.8 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 6.6). Genital ulcers were reported more often among HIV seroconverters than HIV-negative women (13% vs. 7%; P = 0.06) and detection was after HIV acquisition (t+6months aOR, 14.5; 95% CI, 1.6 to 133.9).
CONCLUSIONS
HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.
Identifiants
pubmed: 33587502
doi: 10.1097/QAI.0000000000002641
pii: 00126334-202106010-00009
pmc: PMC8131209
mid: NIHMS1667228
doi:
Substances chimiques
Antibodies, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
789-793Subventions
Organisme : NCI NIH HHS
ID : K07 CA225403
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA134274
Pays : United States
Organisme : NICHD NIH HHS
ID : N01 HD03310
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to disclose.
Références
James C, Harfouche M, Welton NJ, et al. Herpes simplex virus: global infection prevalence and incidence estimates, 2016. Bull World Health Organ. 2020;98:315–329.
Weiss H. Epidemiology of herpes simplex virus type 2 infection in the developing world. Herpes. 2004;11(suppl 1):24A–35A.
Wald A, Zeh J, Selke S, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000;342:844–850.
Johnston C, Corey L. Current concepts for genital herpes simplex virus infection: diagnostics and pathogenesis of genital tract shedding. Clin Microbiol Rev. 2016;29:149–161.
Tronstein E, Johnston C, Huang ML, et al. Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection. JAMA. 2011;305:1441–1449.
Zhu J, Hladik F, Woodward A, et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med. 2009;15:886–892.
Johnson KE, Redd AD, Quinn TC, et al. Effects of HIV-1 and herpes simplex virus type 2 infection on lymphocyte and dendritic cell density in adult foreskins from Rakai, Uganda. J Infect Dis. 2011;203:602–609.
Johnston C, Zhu J, Jing L, et al. Virologic and immunologic evidence of multifocal genital herpes simplex virus 2 infection. J Virol. 2014;88:4921–4931.
Horbul JE, Schmechel SC, Miller BR, et al. Herpes simplex virus-induced epithelial damage and susceptibility to human immunodeficiency virus type 1 infection in human cervical organ culture. PLoS One. 2011;6:e22638.
Looker KJ, Elmes JA, Gottlieb SL, et al. Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis. Lancet Infect Dis. 2017;17:1303–1316.
Phipps W, Saracino M, Magaret A, et al. Persistent genital herpes simplex virus-2 shedding years following the first clinical episode. J Infect Dis. 2011;203:180–187.
Serwadda D, Gray RH, Sewankambo NK, et al. Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. J Infect Dis. 2003;188:1492–1497.
Brown JM, Wald A, Hubbard A, et al. Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe. AIDS. 2007;21:1515–1523.
Mavedzenge SN, Weiss HA, Montgomery ET, et al. Determinants of differential HIV incidence among women in three southern African locations. J Acquir Immune Defic Syndr. 2011;58:89–99.
Baeten JM, Benki S, Chohan V, et al. Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women. AIDS. 2007;21:1771–1777.
Morrison CS, Richardson BA, Mmiro F, et al. Hormonal contraception and the risk of HIV acquisition. AIDS. 2007;21:85–95.
Hogrefe W, Su X, Song J, et al. Detection of herpes simplex virus type 2-specific immunoglobulin G antibodies in African sera by using recombinant gG2, western blotting, and gG2 inhibition. J Clin Microbiol. 2002;40:3635–3640.
Turner AN, Morrison CS, Padian NS, et al. Male circumcision and women's risk of incident chlamydial, gonococcal, and trichomonal infections. Sex Transm Dis. 2008;35:689–695.
Fichorova RN, Chen PL, Morrison CS, et al. The contribution of cervicovaginal infections to the immunomodulatory effects of hormonal contraception. MBio. 2015;6:e00221–e00315.
Nowak RG, Gravitt PE, Morrison CS, et al. Increases in human papillomavirus detection during early HIV infection among women in Zimbabwe. J Infect Dis. 2011;203:1182–1191.
Corey L, Huang ML, Selke S, et al. Differentiation of herpes simplex virus types 1 and 2 in clinical samples by a real-time taqman PCR assay. J Med Virol. 2005;76:350–355.
Kim HN, Wang J, Hughes J, et al. Effect of acyclovir on HIV-1 set point among herpes simplex virus type 2-seropositive persons during early HIV-1 infection. J Infect Dis. 2010;202:734–738.
Mark KE, Wald A, Magaret AS, et al. Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis. 2008;198:1141–1149.
Posavad CM, Wald A, Kuntz S, et al. Frequent reactivation of herpes simplex virus among HIV-1-infected patients treated with highly active antiretroviral therapy. J Infect Dis. 2004;190:693–696.
Tan DH, Raboud JM, Kaul R, et al. Antiretroviral therapy is not associated with reduced herpes simplex virus shedding in HIV coinfected adults: an observational cohort study. BMJ Open. 2014;4:e004210.
Ramaswamy M, Waters A, Smith C, et al. Reconstitution of herpes simplex virus-specific T cell immunity in HIV-infected patients receiving highly active antiretroviral therapy. J Infect Dis. 2007;195:410–415.
Ford ES, Magaret AS, Spak CW, et al. Increase in HSV shedding at initiation of antiretroviral therapy and decrease in shedding over time on antiretroviral therapy in HIV and HSV-2 infected persons. AIDS. 2018;32:2525–2531.
Celum C, Wald A, Hughes J, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2008;371:2109–2119.
Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med. 2010;362:427–439.
Watson-Jones D, Weiss HA, Rusizoka M, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med. 2008;358:1560–1571.
Johnston C, Saracino M, Kuntz S, et al. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials. Lancet (London, England). 2012;379:641–647.
Lu Y, Celum C, Wald A, et al. Acyclovir achieves a lower concentration in African HIV-seronegative, herpes simplex virus 2-seropositive women than in non-African populations. Antimicrob Agents Chemother. 2012;56:2777–2779.