Journal of the European Academy of Dermatology and VenereologyVolume 36, Issue 1 p. e6-e9 Letter to the Editor Varicella-zoster and herpes simplex virus reactivation post-COVID-19 vaccination: a review of 40 cases in an International Dermatology Registry R.A. Fathy, R.A. Fathy Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USASearch for more papers by this authorD.E. McMahon, D.E. McMahon orcid.org/0000-0002-3649-9208 Harvard Medical School, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorC. Lee, C. Lee Department of Dermatology, Las Vegas School of Medicine, University of Nevada, Las Vegas, NV, USASearch for more papers by this authorG.C. Chamberlin, G.C. Chamberlin Medical Practice Evaluation Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorM. Rosenbach, M. Rosenbach Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USASearch for more papers by this authorJ.B. Lipoff, J.B. Lipoff Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USASearch for more papers by this authorA. Tyagi, A. Tyagi Medical Practice Evaluation Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorS.R. Desai, S.R. Desai The University of Texas Southwestern Medical Center, Dallas, TX, USA Innovative Dermatology, Plano, TX, USASearch for more papers by this authorL.E. French, L.E. French Department of Dermatology, University Hospital, Munich University of Ludwig Maximilian, Munich, Germany Dr. Philip Frost, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USASearch for more papers by this authorH.W. Lim, H.W. Lim Department of Dermatology, Henry Ford Health System, Detroit, MI, USASearch for more papers by this authorB.H. Thiers, B.H. Thiers Department of Dermatology and Dermatologic Surgery, Medical University of SC, Charleston, SC, USASearch for more papers by this authorG.J. Hruza, G.J. Hruza Department of Dermatology, St. Louis University, St. Louis, MO, USASearch for more papers by this authorM. Fassett, M. Fassett Department of Dermatology, University of California San Francisco, San Francisco, CA, USASearch for more papers by this authorL.P. Fox, L.P. Fox Department of Dermatology, University of California San Francisco, San Francisco, CA, USASearch for more papers by this authorH.L. Greenberg, H.L. Greenberg Las Vegas Dermatology, Las Vegas, NV, USASearch for more papers by this authorK. Blumenthal, K. Blumenthal Harvard Medical School, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorE.E. Freeman, Corresponding Author E.E. Freeman [email protected] orcid.org/0000-0001-7751-9466 Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA Medical Practice Evaluation Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA *Correspondence: E. Freeman. E-mail: [email protected]Search for more papers by this author R.A. Fathy, R.A. Fathy Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USASearch for more papers by this authorD.E. McMahon, D.E. McMahon orcid.org/0000-0002-3649-9208 Harvard Medical School, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorC. Lee, C. Lee Department of Dermatology, Las Vegas School of Medicine, University of Nevada, Las Vegas, NV, USASearch for more papers by this authorG.C. Chamberlin, G.C. Chamberlin Medical Practice Evaluation Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorM. Rosenbach, M. Rosenbach Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USASearch for more papers by this authorJ.B. Lipoff, J.B. Lipoff Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USASearch for more papers by this authorA. Tyagi, A. Tyagi Medical Practice Evaluation Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorS.R. Desai, S.R. Desai The University of Texas Southwestern Medical Center, Dallas, TX, USA Innovative Dermatology, Plano, TX, USASearch for more papers by this authorL.E. French, L.E. French Department of Dermatology, University Hospital, Munich University of Ludwig Maximilian, Munich, Germany Dr. Philip Frost, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USASearch for more papers by this authorH.W. Lim, H.W. Lim Department of Dermatology, Henry Ford Health System, Detroit, MI, USASearch for more papers by this authorB.H. Thiers, B.H. Thiers Department of Dermatology and Dermatologic Surgery, Medical University of SC, Charleston, SC, USASearch for more papers by this authorG.J. Hruza, G.J. Hruza Department of Dermatology, St. Louis University, St. Louis, MO, USASearch for more papers by this authorM. Fassett, M. Fassett Department of Dermatology, University of California San Francisco, San Francisco, CA, USASearch for more papers by this authorL.P. Fox, L.P. Fox Department of Dermatology, University of California San Francisco, San Francisco, CA, USASearch for more papers by this authorH.L. Greenberg, H.L. Greenberg Las Vegas Dermatology, Las Vegas, NV, USASearch for more papers by this authorK. Blumenthal, K. Blumenthal Harvard Medical School, Massachusetts General Hospital, Boston, MA, USASearch for more papers by this authorE.E. Freeman, Corresponding Author E.E. Freeman [email protected] orcid.org/0000-0001-7751-9466 Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA Medical Practice Evaluation Center, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA *Correspondence: E. Freeman. E-mail: [email protected]Search for more papers by this author First published: 06 September 2021 https://doi.org/10.1111/jdv.17646Citations: 37Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1McMahon DE, Amerson E, Rosenbach M et al. Cutaneous reactions reported after moderna and pfizer COVID-19 vaccination: A Registry-Based Study of 414 Cases. J Am Acad Dermatol 2021. 10.1016/j.jaad.2021.03.092 Web of Science®Google Scholar 2Dooling K, Harpaz R, Radford K et al. The clinical and laboratory diagnosis of Herpes Zoster: how good is it? Open Forum Infectious Diseases. 2016; 3( suppl_1). Oxford University Press, p. 243. 10.1093/ofid/ofw172.110 Google Scholar 3Harbecke R, Oxman MN, Arnold BA et al. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol 2009; 81(7): 1310–1322. 10.1002/jmv.21506 CASPubMedWeb of Science®Google Scholar 4Rodríguez-Jiménez P, Chicharro P, Cabrera LM et al. Varicella-zoster virus reactivation after SARS-CoV-2 BNT162b2 mRNA vaccination: Report of 5 cases. J Am Acad Dermatol Case Rep 2021; 12: 58–59. Google Scholar 5Lee C, Cotter D, Basa J, Greenberg HL. Post COVID-19 vaccine related shingles cases seen at the Las Vegas dermatology clinic and sent to us via social media. J Cosmet Dermatol 2021; 20, 1960–1964. 10.1111/jocd.14210 PubMedWeb of Science®Google Scholar 6Furer V, Zisman D, Kibari A, Rimar D, Paran Y, Elkayam O. Herpes zoster following BNT162b2 mRNA COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series. Rheumatology 2021. doi: 10.1093/rheumatology/keab345 10.1093/rheumatology/keab345 Web of Science®Google Scholar 7Alpalhão M, Filipe P. Herpes Zoster following SARS-CoV-2 vaccination–a series of 4 cases. J Eur Acad Dermatol Venereol 2021. 10.1111/jdv.17555 PubMedWeb of Science®Google Scholar 8Walter R, Hartmann K, Fleisch F, Reinhart WH, Kuhn M. Reactivation of herpesvirus infections after vaccinations? Lancet 1999; 353(9155): 810. 10.1016/S0140-6736(99)00623-6 CASPubMedWeb of Science®Google Scholar 9Blumenthal KG, Saff RR, Freeman EE. Delayed large local reactions to mRNA Vaccines. Reply. N Engl J Med 2021; 384(24): e98. 10.1056/NEJMc2104751 PubMedWeb of Science®Google Scholar 10Siddiqui MS, Hasnain N. Varicella-Zoster Virus Reactivation amid the COVID-19 pandemic-Do we need to be vigilant? A mini review. J Clin Med Kaz 2020; 6(60): 40–43. 10.23950/jcmk/9267 Google Scholar Citing Literature Volume36, Issue1January 2022Pages e6-e9 This article also appears in:JEADV COVID-19 articles ReferencesRelatedInformation

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.

Objective: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. Background: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. Design: Systematic review and meta-analysis of longitudinal studies. Methods: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. Results: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9–3.9] and women (RR, 3.1; 95% CI, 1.7–5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2–2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. Conclusions: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

TUAC0401 Four cities modelling: #2 the dynamic impact of male circumcision and curable STIs on the heterogeneity of HIV epidemics in sub-Saharan Africa simulation results K.K. Orroth, R.G. White, E.E. Freeman, R. Bakker, J.D.F. Habbema, A. Buve, M.C. Boily, J.R. Glynn, R.J. Hayes London School of Hygiene and Tropical Medicine, London, United Kingdom, London School of Hygiene and Tropical Medicine, Department of Epidemiology and Population Health, London, United Kingdom, London School of Hygiene and Tropical Medicine / Harvard Medical School, Boston, United States, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, Institute of Tropical Medicine, STD/HIV Research and Intervention Unit, Antwerp, Belgium, Imperial College, London, United Kingdom Background: The heterogeneity of HIV epidemics within sub-Saharan Africa may be explained by differences in the distribution of biological cofactors such as STIs and male circumcision. Unobserved sexual risk behaviours could also be an important determinant. Methods: The STDSIM model was fitted to the Four Cities Study data for Cotonou, Benin, Yaoundé, Cameroon (low HIV prevalence) Kisumu, Kenya, and Ndola, Zambia (high HIV prevalence). STIs were assumed to increase the per-act probability of HIV transmission by factors ranging from 3 (gonorrhoea and chlamydia) to 25 (chancroid and primary HSV-2). Lack of male circumcision doubled male susceptibility to HIV, syphilis and chancroid. The proportions circumcised in the default scenarios were 100% in Cotonou and Yaounde, 25% in Kisumu and 10% in Ndola. HIV cofactor effects for STIs were removed and the proportions circumcised were varied to determine the simulated impact on HIV spread. Results: In line with data, the simulated adult HIV prevalences in 1997 for the default scenarios were 3.1%, 7.8%, 28.9% and 27.1% in Cotonou, Yaoundé, Kisumu and Ndola, respectively, but after removing the cofactor effect of chancroid, HIV prevalences in 1997 decreased to 2.9%, 2.0%, 1.8% and 1.9%. Increasing the proportion circumcised in Ndola from 10% to 100% reduced HIV prevalence in 1997 to 7%. If the proportion circumcised in Yaoundé was 0%, HIV prevalence was projected to be 28%. The impact of circumcision on HIV in Ndola was mediated largely through its effect on chancroid. Removing the circumcision cofactor effects for HIV, syphilis and chancroid resulted in HIV prevalences of 25.9%, 24.8% and 6.4%, respectively. Conclusions: Lack of male circumcision in East Africa may help explain the development of heterogeneous HIV epidemics in SSA. Model simulations suggest this may be due to higher historical chancroid prevalence in uncircumcised populations, although caution is required given the lack of empirical data on chancroid.

Objective: To determine risk factors for HIV transmission within married couples in four urban populations in sub-Saharan Africa. Methods: Data from a cross-sectional population-based study were used. Representative random samples approximating 1000 men and 1000 women in each of four cities of Kisumu (Kenya), Ndola (Zambia), Cotonou (Benin), and Yaoundé (Cameroon), were interviewed and tested for sexually transmitted infections (STI). Married couples were identified as concordant negative, discordant, or concordant positive for each STI. After excluding concordant HIV negative couples, analysis of behavioural and STI risk factors for HIV positive concordancy was undertaken across the four cities and in each city separately where sample size allowed. Results: Among 221 couples in which at least one member was HIV positive, we found that the only significant risk factor for positive HIV concordancy was herpes simplex type 2 (HSV-2) status. After adjusting for age and city of residence the odds ratio for HIV concordancy compared to couples with neither spouse HSV-2 positive was 3.4 (95% confidence interval, 0.62–18.4) for couples with one partner HSV-2 positive and 8.6 (95% confidence interval, 1.6–45.0) for couples with both partners HSV-2 positive. The same trends were seen in Kisumu and Ndola when they were analysed separately (numbers were small in the other cities). Conclusions: Although cross-sectional studies are not ideal for delineating the sequence of transmission events, this study adds to the evidence that HSV-2 is a key risk factor in promoting HIV transmission.

TUPE0406 - Four cities modelling: #3 the changing role of direct and STI-mediated effects of male circumcision on HIV incidence during epidemics in sub-Saharan Africa Results: The impact of male circumcision was greatest early in the HIV epidemics and due primarily to the indirect effect on STI infections. At this stage of the HIV epidemic it also provided considerable immediate protection to females. By 15 years into the HIV epidemic the impact of male circumcision had declined and was due primarily to the direct effect on susceptibility to HIV infection. At this stage of the HIV epidemic it provided little immediate protection to females, although they may still benefit from falling HIV prevalence in males over the longer-term. Conclusions: In contemporary populations in sub-Saharan Africa, even those with relatively high rates of classical STI infection, the impacts of male circumcision interventions are likely to be due primarily to direct, rather than STI-mediated effects.

TUPE0414 Four cities modelling: #5 simulated effect of HSV-2 prophylactic vaccines on population-level HIV incidence in sub-Saharan Africa E.E. Freeman, R.G. White, K.K. Orroth, R. Bakker, A. Buve, J.D.F. Habbema, M.C. Boily, R.G. Hayes, J.R. Glynn London School of Hygiene and Tropical Medicine / Harvard Medical School, Boston, United States, London School of Hygiene and Tropical Medicine, Infectious Disease Epidemiology Unit, London, United Kingdom, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, Institute of Tropical Medicine, STD/HIV Research and Intervention Unit, Antwerp, Belgium, Imperial College, London, United Kingdom Background: HSV-2 may play an important role in HIV transmission in sub-Saharan Africa. This project explores the effect of a potential prophylactic HSV-2 vaccine on the HIV epidemic in model simulations. Methods: Epidemiological, behavioural, and demographic data from a cross-sectional population based study in four cities (Cotonou, Benin; Yaounde, Cameroon; Kisumu, Kenya; and Ndola, Zambia) were used to inform model parameters. An individual-based stochastic microsimulation model simulated the HSV-2 and HIV epidemics in the four sites. A prophylactic HSV-2 vaccine was introduced into the model in 1997; HIV incidence ten years later was compared to default scenarios. Results: Assuming continuous vaccination of 14y olds and an initial mass vaccination campaign among 14-30y olds, each with 80% coverage, and 15y average duration of immunity, simulated reductions in population-level HIV incidence in the four cities after ten years were 18-25% for a vaccine with 80% efficacy. This decreased to 10-16% and 610% for efficacies of 50% and 30% respectively. Without the initial mass vaccination campaign, the reduction in HIV incidence for 80% efficacy was only 8-9%, demonstrating the importance of a mass campaign for short-term impact on HIV. Conclusions: HSV-2 vaccines of high or moderate efficacy could have a substantial impact on population-level HIV incidence if delivered with high coverage. Initial mass campaigns targeting a wide age-range will greatly hasten the impact of vaccination.