title: Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa.
abstract: BACKGROUND
  Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown.
  
  
  METHODS
  The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness.
  
  
  RESULTS
  Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%.
  
  
  CONCLUSIONS
  These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.
authors.affiliation: Infectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. richard.white@lshtm.ac.uk
authors.forename: R G
authors.initials: RG
authors.lastname: White
authors.forename: E E
authors.initials: EE
authors.lastname: Freeman
authors.forename: K K
authors.initials: KK
authors.lastname: Orroth
authors.forename: R
authors.initials: R
authors.lastname: Bakker
authors.forename: H A
authors.initials: HA
authors.lastname: Weiss
authors.forename: N
authors.initials: N
authors.lastname: O'Farrell
authors.forename: A
authors.initials: A
authors.lastname: Buvé
authors.forename: R J
authors.initials: RJ
authors.lastname: Hayes
authors.forename: J R
authors.initials: JR
authors.lastname: Glynn
mesh_terms: D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D017677:Age Distribution; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology* / Q000517:prevention & control; D015497:HIV-1; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D018258:Herpesvirus 2, Human; D006801:Humans; D015994:Incidence; D008297:Male; D015995:Prevalence
references.citation: Sex Transm Dis. 2002 Apr;29(4):228-38
references.pmid: 11912465
references.citation: J Infect Dis. 2000 Oct;182(4):1090-6
references.pmid: 10979904
references.citation: J Acquir Immune Defic Syndr. 2003 Jun 1;33(2):121-4
references.pmid: 12794542
references.citation: J Infect Dis. 2008 Dec 15;198(12):1804-8
references.pmid: 18928378
references.citation: J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):346-53
references.pmid: 18176323
references.citation: J Infect Dis. 2005 Feb 1;191 Suppl 1:S107-14
references.pmid: 15627220
references.citation: Epidemiol Infect. 2008 Apr;136(4):551-61
references.pmid: 17559692
references.citation: AIDS. 2006 Jan 2;20(1):73-83
references.pmid: 16327322
references.citation: Lancet. 2008 Jun 21;371(9630):2109-19
references.pmid: 18572080
references.citation: J Infect Dis. 2005 Feb 1;191 Suppl 1:S168-78
references.pmid: 15627227
references.citation: AIDS. 2001 Aug;15 Suppl 4:S97-108
references.pmid: 11686471
references.citation: Sex Transm Infect. 2002 Apr;78 Suppl 1:i55-63
references.pmid: 12083448
references.citation: AIDS. 2001 Aug;15 Suppl 4:S117-26
references.pmid: 11686460
references.citation: Sex Transm Infect. 2007 Aug;83 Suppl 1:i17-24
references.pmid: 17405782
references.citation: J Acquir Immune Defic Syndr. 2004 Apr 15;35(5):435-45
references.pmid: 15021308
references.citation: Sex Transm Dis. 2006 Sep;33(9):536-44
references.pmid: 16778738
references.citation: Sex Transm Infect. 2007 Aug;83 Suppl 1:i5-16
references.pmid: 17405781
references.citation: AIDS. 2008 Sep 12;22(14):1841-50
references.pmid: 18753931
references.citation: JAMA. 1998 Jul 1;280(1):61-6
references.pmid: 9660365
references.citation: J Acquir Immune Defic Syndr. 2008 Sep 1;49(1):77-83
references.pmid: 18667923
references.citation: AIDS. 2002 Dec 6;16(18):2425-30
references.pmid: 12461416
references.citation: AIDS. 2001 Aug;15 Suppl 4:S5-14
references.pmid: 11686465
references.citation: J Acquir Immune Defic Syndr. 2004 Dec 1;37(4):1500-13
references.pmid: 15602129
references.citation: J Infect Dis. 2007 Nov 15;196(10):1500-8
references.pmid: 18008230
references.citation: Bull World Health Organ. 2004 Jun;82(6):447-53
references.pmid: 15356938
references.citation: AIDS. 1999 Mar 11;13(4):536-7
references.pmid: 10197391
references.citation: AIDS. 2006 Jan 9;20(2):261-7
references.pmid: 16511420
references.citation: Drugs. 1996 Nov;52(5):754-72
references.pmid: 9118821
references.citation: AIDS. 2000 Mar 31;14(5):573-93
references.pmid: 10780720
references.citation: N Engl J Med. 2007 Feb 22;356(8):790-9
references.pmid: 17314338
references.citation: J Infect Dis. 2002 Jan 1;185(1):45-52
references.pmid: 11756980
references.citation: J Infect Dis. 1999 Jan;179(1):16-24
references.pmid: 9841817
references.citation: J Infect Dis. 1999 Nov;180(5):1459-65
references.pmid: 10515804
references.citation: Ann Intern Med. 1989 Jun 1;110(11):882-7
references.pmid: 2541645
references.citation: Clin Infect Dis. 2004 Nov 1;39 Suppl 5:S240-7
references.pmid: 15494895
references.citation: AIDS. 2007 Jul 31;21(12):1569-78
references.pmid: 17630552
references.citation: J Infect Dis. 2002 Dec 15;186(12):1718-25
references.pmid: 12447756
references.citation: J Infect Dis. 2003 Nov 15;188(10):1492-7
references.pmid: 14624374
references.citation: Lancet. 2001 Apr 14;357(9263):1149-53
references.pmid: 11323041
references.citation: AIDS. 1998 Oct 1;12(14):1889-98
references.pmid: 9792390
references.citation: J Infect Dis. 1998 Dec;178(6):1616-22
references.pmid: 9815213