Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study

John Bradley, Sian Floyd, Estelle Piwowar-Manning, Oliver Laeyendecker, Alicia Young, Nomtha Bell-Mandla, Justin Bwalya, Peter Bock, Sarah Fidler, Helen Ayles, Richard J Hayes, HPTN 071 (PopART) Study Team, John Bradley, Sian Floyd, Estelle Piwowar-Manning, Oliver Laeyendecker, Alicia Young, Nomtha Bell-Mandla, Justin Bwalya, Peter Bock, Sarah Fidler, Helen Ayles, Richard J Hayes, HPTN 071 (PopART) Study Team

Abstract

Background: Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels.

Methods: The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence.

Results: A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001).

Conclusions: There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.

Figures

Figure 1.
Figure 1.
Herpes simplex virus type 2 (HSV2) prevalence, by sex, country, and age group, in all age groups (left) and those aged

Figure 2.

Community-level association between herpes simplex…

Figure 2.

Community-level association between herpes simplex virus type 2 (HSV2) prevalence and human immunodeficiency…

Figure 2.
Community-level association between herpes simplex virus type 2 (HSV2) prevalence and human immunodeficiency virus (HIV) prevalence.

Figure 3.

Community-level association between lifetime number…

Figure 3.

Community-level association between lifetime number of sex partners and herpes simplex virus type…

Figure 3.
Community-level association between lifetime number of sex partners and herpes simplex virus type 2 (HSV2) prevalence.
Figure 2.
Figure 2.
Community-level association between herpes simplex virus type 2 (HSV2) prevalence and human immunodeficiency virus (HIV) prevalence.
Figure 3.
Figure 3.
Community-level association between lifetime number of sex partners and herpes simplex virus type 2 (HSV2) prevalence.

References

    1. Looker KJ, Magaret AS, May MT et al. . Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS One 2015; 10:e0140765.
    1. Obasi A, Mosha F, Quigley M et al. . Antibody to herpes simplex virus type 2 as a marker of sexual risk behavior in rural Tanzania. J Infect Dis 1999; 179:16–24.
    1. Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis 2002; 186(Suppl 1):S3–28.
    1. Weiss HA, Buvé A, Robinson NJ et al. ; Study Group on Heterogeneity of HIV Epidemics in African Cities The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations. AIDS 2001; 15(Suppl 4):S97–108.
    1. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006; 20:73–83.
    1. del Mar Pujades Rodríguez M, Obasi A, Mosha F et al. . Herpes simplex virus type 2 infection increases HIV incidence: a prospective study in rural Tanzania. AIDS 2002; 16:451–62.
    1. 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; 21:1515–23.
    1. Reynolds SJ, Risbud AR, Shepherd ME et al. . Recent herpes simplex virus type 2 infection and the risk of human immunodeficiency virus type 1 acquisition in India. J Infect Dis 2003; 187:1513–21.
    1. Sobngwi-Tambekou J, Taljaard D, Lissouba P et al. . Effect of HSV-2 serostatus on acquisition of HIV by young men: results of a longitudinal study in Orange Farm, South Africa. J Infect Dis 2009; 199:958–64.
    1. Todd J, Riedner G, Maboko L et al. . Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania. PLoS One 2013; 8:e59037.
    1. Johnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: a systematic review and meta-analysis. Sex Transm Dis 2008; 35:946–59.
    1. Freeman EE, Orroth KK, White RG 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. Sex Transm Infect 2007; 83(Suppl 1):i17–24.
    1. White RG, Orroth KK, Glynn JR et al. . Treating curable sexually transmitted infections to prevent HIV in Africa: still an effective control strategy?J Acquir Immune Defic Syndr 2008; 47:346–53.
    1. Buvé A, Caraël M, Hayes RJ et al. ; Study Group on Heterogeneity of HIV Epidemics in African Cities The multicentre study on factors determining the differential spread of HIV in four African cities: summary and conclusions. AIDS 2001; 15(Suppl 4):S127–31.
    1. Orroth KK, Freeman EE, Bakker R et al. . Understanding the differences between contrasting HIV epidemics in east and west Africa: results from a simulation model of the Four Cities Study. Sex Transm Infect 2007; 83(Suppl 1):i5–16.
    1. 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; 15:886–92.
    1. 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; 203:602–9.
    1. Watson-Jones D, Weiss HA, Rusizoka M et al. ; HSV trial team; Steering and Data Monitoring Committees Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med 2008; 358:1560–71.
    1. Celum C, Wald A, Hughes J et al. ; HPTN 039 Protocol Team 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 2008; 371:2109–19.
    1. Celum C, Wald A, Lingappa JR et al. ; Partners in Prevention HSV/HIV Transmission Study Team Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med 2010; 362:427–39.
    1. Freeman EE, White RG, Bakker R et al. . Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa. Vaccine 2009; 27:940–6.
    1. Belshe RB, Leone PA, Bernstein DI et al. ; Herpevac Trial for Women Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med 2012; 366:34–43.
    1. Bernstein DI, Wald A, Warren T et al. . Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial. J Infect Dis 2017; 215:856–64.
    1. Gottlieb SL, Deal CD, Giersing B et al. . The global roadmap for advancing development of vaccines against sexually transmitted infections: Update and next steps. Vaccine 2016; 34:2939–47.
    1. Hayes R, Floyd S, Schaap A et al. ; HPTN 071 (PopART) Study Team A universal testing and treatment intervention to improve HIV control: One-year results from intervention communities in Zambia in the HPTN 071 (PopART) cluster-randomised trial. PLoS Med 2017; 14:e1002292.
    1. Patel EU, Manucci J, Kahle EM et al. . Precision of the Kalon Herpes Simplex Virus Type 2 IgG ELISA: an international inter-laboratory assessment. BMC Infect Dis 2015; 15:398.
    1. Victora CG, Huttly SR, Fuchs SC, Olinto MT. The role of conceptual frameworks in epidemiological analysis: a hierarchical approach. Int J Epidemiol 1997; 26:224–7.
    1. Looker KJ, Elmes JAR, Gottlieb SL et al. . Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis. Lancet Infect Dis 2017; 17:1303–16.
    1. Omori R, Nagelkerke N, Abu-Raddad LJ. HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study. Sex Transm Infect 2017. doi: 10.1136/sextrans-2017-053336.

Source: PubMed

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