- Email: [email protected]
A fresh look at an old problem
Comment
The incidence of HIV infection has not changed in a decade. Since 2005, about 2·6 million people have become newly infected with HIV annually.1 Young women, particularly adolescent girls, account for a disproportionate number of new HIV infections. Development of successful strategies to prevent HIV acquisition might require more creative approaches to meet the needs of the most susceptible populations, including exploration of the role of sexually transmitted infections, such as herpes simplex virus type 2 (HSV-2), in HIV infection.2 HSV-2 contributes to the high incidence of HIV; evidence has shown that HSV-2 infection increases the risk of HIV infection.3,4 In The Lancet Infectious Diseases, Katharine Looker and colleagues5 provide the first systematic review and meta-analysis (to May 2017) in over a decade to assess the effect of HSV-2 infection on subsequent HIV acquisition. They analysed 57 longitudinal studies and derived pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV acquisition. Their findings for prevalent HSV-2 infection were in line with data from previous studies and showed that the risk of HIV acquisition was roughly tripled in general populations and almost doubled in high-risk populations. Their pooled estimates for the effect of incident HSV-2 infection on HIV infection showed that incident HSV-2 infection was associated with a five times increase in the risk of HIV in general populations and a three times increase in the risk of HIV in high-risk populations. Estimates for HSV-2 infection in 2012 underscored the magnitude of the problem, which was particularly serious for women and girls in Africa.6 About 417 million people were living with HSV-2 worldwide in 2012, with women accounting for 64% of infected individuals. Although only a quarter of women infected with HSV-2 were aged 15–24 years, two-thirds of new infections came from this age group, suggesting that policy responses must focus on young women and adolescent girls. In 2012, the estimated overall prevalence of HSV-2 infection in African women aged 15–49 years was 38%. About 135 million people in Africa aged 15–49 years were infected with HSV-2; 22·4 million were women aged 15–24 years. Another 6·4 million people
in Africa were newly infected with HSV-2; 2·3 million were women aged 15–24 years. These numbers are particularly concerning because women in Africa aged 15–24 years had the highest number of new HIV infections of all age groups in 2015.7 Strategies to mitigate the risk of HIV in populations with a high HSV-2 prevalence have been explored. One strategy tested whether HSV-2 suppressive therapy with acyclovir (400 mg twice per day) could reduce the risk of HIV. Data from two studies8,9 showed that acyclovir did not decrease the incidence of HIV in HSV-2 infected individuals. Another study10 assessed the effect of acyclovir on HIV transmission from a person coinfected with HIV and HSV-2 who was not on antiretrovirals to a partner who was HIV negative and who might or might not have been infected with HSV-2. Despite a decrease in HIV viral loads and frequency of genital ulcers in the coinfected partner, daily acyclovir therapy did not reduce the risk of HIV transmission. A multipurpose prevention technology that provides pre-exposure prophylaxis for HSV-2, HIV, or both is another option. Data from the CAPRISA 004 HIV prevention trial11 of 889 women in South Africa showed that vaginally applied 1% tenofovir gel reduced HIV infection by 39% and, unexpectedly, HSV-2 infection by 51%. Subsequent phase 3 trials showed that the gel was not effective against HIV acquisition, which might be attributed to low adherence to the study products. Oral emtricitabine-tenofovir (Truvada) is indicated for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV infection in high-risk adults. Although not indicated for HSV-2, Truvada reduced HSV-2 acquisition in heterosexual men who were HIV-1 negative and in women with HIV-1 and HSV-2 coinfected partners by 33%.12 However, Truvada is not an option for all at-risk (HIV, HSV-2, or HIV and HSV-2) individuals because of its poor availability in sub-Saharan Africa and other low-income regions, user acceptability and adherence issues, and modest efficacy against HSV-2. Therefore, other multipurpose prevention technologies for HSV-2 and HIV are needed to give individuals a broad range of prevention options and to target the lifestyles and preferences of the most susceptible populations, including young women in Africa who have the highest incidence of HIV and HSV-2 worldwide.13
www.thelancet.com/infection Published online August 23, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30493-0
Dr P Marazzi/Science Photo Library
A fresh look at an old problem
Lancet Infect Dis 2017 Published Online August 23, 2017 http://dx.doi.org/10.1016/ S1473-3099(17)30493-0 See Online/Articles http://dx.doi.org/10.1016/ S1473-3099(17)30405-X
1
Comment
Thomas M Zydowsky
7
Population Council, New York, NY 10065, USA [email protected]
8
I declare no competing interests. Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY NC ND 4.0 license. 1 2 3 4
5
6
2
GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV 2016; 3: e361–87. Fernández-Romero JA, Deal C, Herold BC, et al. Multipurpose prevention technologies: the future of HIV and STI protection. Trends Microbiol 2015; 23: 429–36. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis 2002; 185: 45–52. 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. 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; published online August 23. http://dx.doi.org/10.1016/S1473-3099(17)30405-X. Looker KJ, Magaret AS, Turner KM, Vickerman P, Gottlieb SL, Newman LM. Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. PLoS One 2015; 10: e114989.
9 10 11 12
13
UNAIDS. Prevention gap report. 2016. http://www.unaids.org/sites/ default/files/media_asset/2016-prevention-gap-report_en.pdf (accessed July 28, 2017). Celum C, Wald A, Hughes J, et al, for the 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. Watson-Jones D, Weiss HA, Rusizoka M, et al, for the 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. Celum C, Wald A, Lingappa JR, et al, for the 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. Abdool Karim SS, Abdool Karim Q, Kharsany AB, et al, for the CAPRISA 004 Trial Group. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med 2015; 373: 530–39. Celum C, Morrow RA, Donnell D, et al, for the Partners PrEP Study Team. Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial. Ann Intern Med 2014; 161: 11–19. Ugaonkar SR, Wesenberg A, Wilk J, et al. A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy. J Control Release 2015; 213: 57–68.
www.thelancet.com/infection Published online August 23, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30493-0
The incidence of HIV infection has not changed in a decade. Since 2005, about 2·6 million people have become newly infected with HIV annually.1 Young women, particularly adolescent girls, account for a disproportionate number of new HIV infections. Development of successful strategies to prevent HIV acquisition might require more creative approaches to meet the needs of the most susceptible populations, including exploration of the role of sexually transmitted infections, such as herpes simplex virus type 2 (HSV-2), in HIV infection.2 HSV-2 contributes to the high incidence of HIV; evidence has shown that HSV-2 infection increases the risk of HIV infection.3,4 In The Lancet Infectious Diseases, Katharine Looker and colleagues5 provide the first systematic review and meta-analysis (to May 2017) in over a decade to assess the effect of HSV-2 infection on subsequent HIV acquisition. They analysed 57 longitudinal studies and derived pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV acquisition. Their findings for prevalent HSV-2 infection were in line with data from previous studies and showed that the risk of HIV acquisition was roughly tripled in general populations and almost doubled in high-risk populations. Their pooled estimates for the effect of incident HSV-2 infection on HIV infection showed that incident HSV-2 infection was associated with a five times increase in the risk of HIV in general populations and a three times increase in the risk of HIV in high-risk populations. Estimates for HSV-2 infection in 2012 underscored the magnitude of the problem, which was particularly serious for women and girls in Africa.6 About 417 million people were living with HSV-2 worldwide in 2012, with women accounting for 64% of infected individuals. Although only a quarter of women infected with HSV-2 were aged 15–24 years, two-thirds of new infections came from this age group, suggesting that policy responses must focus on young women and adolescent girls. In 2012, the estimated overall prevalence of HSV-2 infection in African women aged 15–49 years was 38%. About 135 million people in Africa aged 15–49 years were infected with HSV-2; 22·4 million were women aged 15–24 years. Another 6·4 million people
in Africa were newly infected with HSV-2; 2·3 million were women aged 15–24 years. These numbers are particularly concerning because women in Africa aged 15–24 years had the highest number of new HIV infections of all age groups in 2015.7 Strategies to mitigate the risk of HIV in populations with a high HSV-2 prevalence have been explored. One strategy tested whether HSV-2 suppressive therapy with acyclovir (400 mg twice per day) could reduce the risk of HIV. Data from two studies8,9 showed that acyclovir did not decrease the incidence of HIV in HSV-2 infected individuals. Another study10 assessed the effect of acyclovir on HIV transmission from a person coinfected with HIV and HSV-2 who was not on antiretrovirals to a partner who was HIV negative and who might or might not have been infected with HSV-2. Despite a decrease in HIV viral loads and frequency of genital ulcers in the coinfected partner, daily acyclovir therapy did not reduce the risk of HIV transmission. A multipurpose prevention technology that provides pre-exposure prophylaxis for HSV-2, HIV, or both is another option. Data from the CAPRISA 004 HIV prevention trial11 of 889 women in South Africa showed that vaginally applied 1% tenofovir gel reduced HIV infection by 39% and, unexpectedly, HSV-2 infection by 51%. Subsequent phase 3 trials showed that the gel was not effective against HIV acquisition, which might be attributed to low adherence to the study products. Oral emtricitabine-tenofovir (Truvada) is indicated for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV infection in high-risk adults. Although not indicated for HSV-2, Truvada reduced HSV-2 acquisition in heterosexual men who were HIV-1 negative and in women with HIV-1 and HSV-2 coinfected partners by 33%.12 However, Truvada is not an option for all at-risk (HIV, HSV-2, or HIV and HSV-2) individuals because of its poor availability in sub-Saharan Africa and other low-income regions, user acceptability and adherence issues, and modest efficacy against HSV-2. Therefore, other multipurpose prevention technologies for HSV-2 and HIV are needed to give individuals a broad range of prevention options and to target the lifestyles and preferences of the most susceptible populations, including young women in Africa who have the highest incidence of HIV and HSV-2 worldwide.13
www.thelancet.com/infection Published online August 23, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30493-0
Dr P Marazzi/Science Photo Library
A fresh look at an old problem
Lancet Infect Dis 2017 Published Online August 23, 2017 http://dx.doi.org/10.1016/ S1473-3099(17)30493-0 See Online/Articles http://dx.doi.org/10.1016/ S1473-3099(17)30405-X
1
Comment
Thomas M Zydowsky
7
Population Council, New York, NY 10065, USA [email protected]
8
I declare no competing interests. Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY NC ND 4.0 license. 1 2 3 4
5
6
2
GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV 2016; 3: e361–87. Fernández-Romero JA, Deal C, Herold BC, et al. Multipurpose prevention technologies: the future of HIV and STI protection. Trends Microbiol 2015; 23: 429–36. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis 2002; 185: 45–52. 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. 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; published online August 23. http://dx.doi.org/10.1016/S1473-3099(17)30405-X. Looker KJ, Magaret AS, Turner KM, Vickerman P, Gottlieb SL, Newman LM. Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. PLoS One 2015; 10: e114989.
9 10 11 12
13
UNAIDS. Prevention gap report. 2016. http://www.unaids.org/sites/ default/files/media_asset/2016-prevention-gap-report_en.pdf (accessed July 28, 2017). Celum C, Wald A, Hughes J, et al, for the 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. Watson-Jones D, Weiss HA, Rusizoka M, et al, for the 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. Celum C, Wald A, Lingappa JR, et al, for the 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. Abdool Karim SS, Abdool Karim Q, Kharsany AB, et al, for the CAPRISA 004 Trial Group. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med 2015; 373: 530–39. Celum C, Morrow RA, Donnell D, et al, for the Partners PrEP Study Team. Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial. Ann Intern Med 2014; 161: 11–19. Ugaonkar SR, Wesenberg A, Wilk J, et al. A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy. J Control Release 2015; 213: 57–68.
www.thelancet.com/infection Published online August 23, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30493-0