Background More than ten years have elapsed since human papillomavirus (HPV) vaccination was implemented. We performed a systematic review and meta-analysis of the population-level impact of female-only HPV vaccination on HPV infections, anogenital wart diagnoses (AGW) and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination. Methods We updated our prior review (01/01/2007-28/02/2014), by searching Medline and Embase (01/02/2014-11/10/2018) for studies that examined changes, between pre-and post-vaccination periods, in HPV infections, AGW, or CIN2+. We stratified all analyses by sex, age, and years since HPV vaccination introduction. We used random-effects models to estimate pooled relative risks and performed subgroup analysis to identify the main sources of heterogeneity. Findings We identified 65 eligible articles conducted in 14 high-income countries. After 5-8 years of vaccination, HPV-16/18, AGW, and CIN2+ decreased significantly by about 80%, 70%, and 50% among girls aged 15-19 years and by 65%, 55%, and 30% among women aged 20-24 years. Significant cross-protection and herd effects were also observed. HPV-31/33/45 decreased significantly by 50% among girls aged 15-19 years and AGW decreased significantly by 30-50% among boys/men aged 15-24 years. After 5-8 years of vaccination, countries with multi-cohort vaccination and high coverage (≥50%) had greater reductions in AGW, 44 and 85 percentage points among girls and boys aged 15-19 years, respectively, than countries with single-cohort vaccination and/or low vaccination coverage. Interpretation Our meta-analysis, including data from >60 million individuals from 14 high-income countries, shows a substantial impact of female-only HPV vaccination programs on AGW among girls/women and boys/men, and HPV infections and CIN2+ among girls/women. In addition, programs with multi-cohort vaccination and high vaccination coverage lead to greater and faster direct impact and herd effects. CONTRIBUTIONS MD, MB, and MCB conceived the study. MD, EB and NP did the literature search and performed the analysis. MB and MCB participated in the analysis. MD and MB co-drafted the first version of the article.

Background A 2017 systematic review and meta-analysis of 55 prospective studies found the adjusted risk of HIV acquisition to be at least tripled in individuals with herpes simplex virus type 2 (HSV-2) infection. We aimed to assess the potential contribution of HSV-2 infection to HIV incidence, given an effect of HSV-2 on HIV acquisition. MethodsWe used a classic epidemiological formula to estimate the global and regional (WHO regional) population attributable fraction (PAF) and number of incident HIV infections attributable to HSV-2 infection by age (15-24 years, 25-49 years, and 15-49 years), sex, and timing of HSV-2 infection (established vs recently acquired). Estimates were calculated by incorporating HSV-2 and HIV infection data with pooled relative risk (RR) estimates for the effect of HSV-2 infection on HIV acquisition from a systematic review and meta-analysis. Because HSV-2 and HIV have shared sexual and other risk factors, in addition to HSV-related biological factors that increase HIV risk, we only used RR estimates that were adjusted for potential confounders. Findings An estimated 420 000 (95% uncertainty interval 317 000-546 000; PAF 29•6% [22•9-37•1]) of 1•4 million sexually acquired incident HIV infections in individuals aged 15-49 years in 2016 were attributable to HSV-2 infection. The contribution of HSV-2 to HIV was largest for the WHO African region (PAF 37•1% [28•7-46•3]), women (34•8% [23•5-45•0]), individuals aged 25-49 years (32•4% [25•4-40•2]), and established HSV-2 infection (26•8% [19•7-34•5]).Interpretation A large burden of HIV is likely to be attributable to HSV-2 infection, even if the effect of HSV-2 infection on HIV had been imperfectly measured in studies providing adjusted RR estimates, potentially because of residual confounding. The contribution is likely to be greatest in areas where HSV-2 is highly prevalent, particularly Africa. New preventive interventions against HSV-2 infection could not only improve the quality of life of millions of people by reducing the prevalence of herpetic genital ulcer disease, but could also have an additional, indirect effect on HIV transmission.Funding WHO.

IntroductionHerpes simplex virus (HSV) infection can cause painful, recurrent genital ulcer disease (GUD), which can have a substantial impact on sexual and reproductive health. HSV-related GUD is most often due to HSV type 2 (HSV-2), but may also be due to genital HSV type 1 (HSV-1), which has less frequent recurrent episodes than HSV-2. The global burden of GUD has never been quantified. Here we present the first global and regional estimates of GUD due to HSV-1 and HSV-2 among women and men aged 15–49 years old.MethodsWe developed a natural history model reflecting the clinical course of GUD following HSV-2 and genital HSV-1 infection, informed by a literature search for data on model parameters. We considered both diagnosed and undiagnosed symptomatic infection. This model was then applied to existing infection estimates and population sizes for 2016. A sensitivity analysis was carried out varying the assumptions made.ResultsWe estimated that 187 million people aged 15–49 years had at least one episode of HSV-related GUD globally in 2016: 5.0% of the world’s population. Of these, 178 million (95% of those with HSV-related GUD) had HSV-2 compared with 9 million (5%) with HSV-1. GUD burden was highest in Africa, and approximately double in women compared with men. Altogether there were an estimated 8 billion person-days spent with HSV-related GUD globally in 2016, with 99% of days due to HSV-2. Taking into account parameter uncertainty, the percentage with at least one episode of HSV-related GUD ranged from 3.2% to 7.9% (120–296 million). However, the estimates were sensitive to the model assumptions.ConclusionOur study represents a first attempt to quantify the global burden of HSV-related GUD, which is large. New interventions such as HSV vaccines, antivirals or microbicides have the potential to improve the quality of life of millions of people worldwide.

Background: To date different vaginal gel microbicides have been evaluated in phase 2b/3 trials, but none have demonstrated effectiveness for preventing HIV infection. Failure to demonstrate effectiveness however does not necessarily indicate that a product is truly inefficacious, as several sources of efficacy dilution may compromise our ability to identify products that may have been truly efficacious.