Modelling the interactions between herpes simplex virus type 2 and HIV: implications for the HIV epidemic in southern India

Background The role of herpes simplex virus type 2 (HSV-2) in the HIV epidemic and the potential impact of HSV-2 suppressive therapy have previously been explored only within the context of sub-Saharan Africa. In this analysis, modelling is used to estimate the contribution of HSV-2 to HIV transmission from clients to female sex workers (FSW) in a southern Indian setting and the maximum potential impact of ‘perfect’ HSV-2 suppressive therapy on HIV incidence. Methods A dynamic HSV-2/HIV model was developed, parameterised and fitted to Mysore data. The model estimated the attributable fractions of HIV infections due to HSV-2. Multivariate sensitivity analyses and regression analyses were conducted. Results The model suggests that 36% (95% CI 22% to 62%) of FSW HIV infections were due to HSV-2, mostly through HSV-2 asymptomatic shedding. Even if HSV-2 suppressive therapy could eliminate the effect of HSV-2 on HIV infectivity among all co-infected clients, only 15% (95% CI 3% to 41%) of HIV infections among FSW would have been averted. 36% (95% CI 18% to 61%) of HIV infections among HSV-2-infected FSW could have been averted if suppressive therapy reduced their risk of HIV acquisition to that of HSV-2-uninfected FSW. Conclusions HSV-2 contributes substantially to HIV in this southern Indian context. However, even in the best case scenario, HSV-2 suppressive therapy is unlikely to reduce HIV transmission or acquisition by more than 50% (as aimed for in recent trials), because of the limited strength of the interaction effect between HSV-2 and HIV.

[1]  J. Baeten,et al.  Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial , 2010, The Lancet.

[2]  James P. Hughes,et al.  Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. , 2010, The New England journal of medicine.

[3]  A. Puren,et al.  Improvement in healing and reduction in HIV shedding with episodic acyclovir therapy as part of syndromic management among men: a randomized, controlled trial. , 2009, The Journal of infectious diseases.

[4]  Christophe Fraser,et al.  Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load , 2009, AIDS.

[5]  H. Rees,et al.  Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomized placebo-controlled trial in South Africa , 2009, AIDS.

[6]  Zaid Chalabi,et al.  Dynamic Modeling of Herpes Simplex Virus Type-2 (HSV-2) Transmission: Issues in Structural Uncertainty , 2009, Bulletin of mathematical biology.

[7]  Richard G. White,et al.  Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa , 2009, Vaccine.

[8]  E. Gassiat,et al.  Transmission probabilities of HIV and herpes simplex virus type 2, effect of male circumcision and interaction: a longitudinal study in a township of South Africa , 2009, AIDS.

[9]  J. Baeten,et al.  Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial. , 2008, The Journal of infectious diseases.

[10]  S. Vermund,et al.  Impact of small reductions in plasma HIV RNA levels on the risk of heterosexual transmission and disease progression , 2008, AIDS.

[11]  E. Freeman,et al.  Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa , 2008, Sexually Transmitted Infections.

[12]  H. Balfour,et al.  Coinfection alters the playing field: herpesviruses induce acyclovir to inhibit HIV. , 2008, Cell host & microbe.

[13]  R. Schinazi,et al.  Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues. , 2008, Cell host & microbe.

[14]  S. Whitehead,et al.  Suppressive Acyclovir Therapy Reduces HIV Cervicovaginal Shedding in HIV- and HSV-2-Infected Women, Chiang Rai, Thailand , 2008, Journal of acquired immune deficiency syndromes.

[15]  A. Ouedraogo,et al.  Herpes simplex virus and HIV-1: deciphering viral synergy. , 2008, The Lancet. Infectious diseases.

[16]  H. Weiss,et al.  Roles of clinical and subclinical reactivated herpes simplex virus type 2 infection and human immunodeficiency virus type 1 (HIV-1)-induced immunosuppression on genital and plasma HIV-1 levels. , 2008, The Journal of infectious diseases.

[17]  H. Weiss,et al.  Effect of HIV-1 and antiretroviral therapy on herpes simplex virus type 2: a prospective study in African women , 2008, Sexually Transmitted Infections.

[18]  J. Fuchs,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 , 2008, The Lancet.

[19]  S. Self,et al.  Genital Herpes Has Played a More Important Role than Any Other Sexually Transmitted Infection in Driving HIV Prevalence in Africa , 2008, PloS one.

[20]  Louise Knight,et al.  Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. , 2008, The New England journal of medicine.

[21]  Connie Celum,et al.  Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. , 2007, The Journal of infectious diseases.

[22]  R. Hayes,et al.  Cervicovaginal HIV-1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes , 2007, AIDS.

[23]  E. Freeman,et al.  Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics , 2007, Sexually Transmitted Infections.

[24]  A. Wald,et al.  Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation , 2007, The Journal of experimental medicine.

[25]  R. Kaul,et al.  Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract , 2007, AIDS.

[26]  Vincent Foulongne,et al.  Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. , 2007, The New England journal of medicine.

[27]  J. Habbema,et al.  Empirical Observations Underestimate the Proportion of Human Immunodeficiency Virus Infections Attributable to Sexually Transmitted Diseases in the Mwanza and Rakai Sexually Transmitted Disease Treatment Trials: Simulation Results , 2006, Sexually transmitted diseases.

[28]  Richard J Hayes,et al.  Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies , 2006, AIDS.

[29]  Richard G. White,et al.  Can Population Differences Explain the Contrasting Results of the Mwanza, Rakai, and Masaka HIV/Sexually Transmitted Disease Intervention Trials?: A Modeling Study , 2004, Journal of acquired immune deficiency syndromes.

[30]  Sally Blower,et al.  Calculating the contribution of herpes simplex virus type 2 epidemics to increasing HIV incidence: treatment implications. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  A. Wald,et al.  Genital herpes and human immunodeficiency virus: double trouble. , 2004, Bulletin of the World Health Organization.

[32]  T. Quinn,et al.  The Effects of Herpes Simplex Virus-2 on HIV-1 Acquisition and Transmission: A Review of Two Overlapping Epidemics , 2004, Journal of acquired immune deficiency syndromes.

[33]  H. Weiss,et al.  Epidemiology of herpes simplex virus type 2 infection in the developing world. , 2004, Herpes : the journal of the IHMF.

[34]  R. McClelland,et al.  Association between cervical shedding of herpes simplex virus and HIV-1 , 2002, AIDS.

[35]  Jennifer S. Smith,et al.  Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. , 2002, The Journal of infectious diseases.

[36]  S. D. de Vlas,et al.  Can Behavior Change Explain Increases in the Proportion of Genital Ulcers Attributable to Herpes in Sub-Saharan Africa?: A Simulation Modeling Study , 2002, Sexually transmitted diseases.

[37]  R. Hayes,et al.  Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: opportunities for intervention. , 2000, The Journal of infectious diseases.

[38]  J. Margolick,et al.  AIDS onset at high CD4+ cell levels is associated with high HIV load. , 2000, AIDS research and human retroviruses.

[39]  J. Feldman,et al.  Increased Genital Shedding of Herpes Simplex Virus Type 2 in HIV-Seropositive Women , 1995, Annals of Internal Medicine.

[40]  B. Thiers 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 , 2009 .

[41]  J. Bartlett,et al.  Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes , 2004 .

[42]  A. Wald,et al.  Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. , 2002, The Journal of infectious diseases.