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Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission Jeffrey Pudney, Zoon Wangu, Lori Panther, Et Al

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Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission Jeffrey Pudney, Zoon Wangu, Lori Panther, Et Al Journal Club: Journal of Infectious Diseases 13th Feb, 2019 Dr Alisa Pollack, SSHC HIV Hepatitis HPV Herpes Substantial Decline in Prevalence of Vaccine-Type and Nonvaccine-Type Human Papillomavirus (HPV) in Vaccinated and Unvaccinated Girls Berit Feiring, Ida Laake, Irene Kraus Christiansen, et al. What?: Estimation of the impact of quadrivalent HPV vaccination in Norway Why?: This is the first analysis of a population where there was no catch-up vaccination for older girls/women (only 12 year olds were vaccinated) How?: 17,749 17yo girls submitted urine samples (in return for 2 movie tickets) - Approximately two thirds were unvaccinated (born 1994 and 1996), and one third were the first vaccinated cohort (born 1997) - Tested by PCR for 37 HPV genotypes (incl low and high risk types) Substantial Decline in Prevalence of Vaccine-Type and Nonvaccine-Type Human Papillomavirus (HPV) in Vaccinated and Unvaccinated Girls Berit Feiring, Ida Laake, Irene Kraus Christiansen, et al. Results: Vaccination works. Condylomata Acuminata (Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission Jeffrey Pudney, Zoon Wangu, Lori Panther, et al. What?: 1. Examination for HIV target cells in anogenital warts compared to anatomically matched control skin samples 2. Pilot study of in vitro HIV infection of anogenital warts versus control skin Why?: A number of recent studies have shown an increased risk of HIV acquisition in individuals with anogenital warts but the mechanisms are unclear. How?: 1. Archived samples of biopsied warts from 91 subjects were examined for HIV target cells (CD1a dendritic cells, CD4 T lymphocytes, CD68 macrophages). 2. In vitro HIV infection of donor-matched samples of excised anal warts and normal anal epithelium from 8 HIV-negative men. Condylomata Acuminata (Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission Jeffrey Pudney, Zoon Wangu, Lori Panther, et al. Results 1: Anogenital warts contained significantly more HIV target cells than normal anogenital skin. In samples from 31 HIV-infected individuals on treatment, zero stained positive for p24 antigen. Condylomata Acuminata (Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission Jeffrey Pudney, Zoon Wangu, Lori Panther, et al. Results 2: 2 out of 8 anogenital wart specimens showed definitive HIV infection after in vitro inoculation 0 out of 8 normal anogenital skin samples showed infection (Not statistically significant) The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study Golnaz Namazi, Jesse M. Fajnzylber, Evgenia Aga, et al. What?: Characterisation of post-treatment controllers - people who maintain HIV suppression after interruption of anti-retroviral treatment. Why?: Little is known about these rare individuals. They may provide insight into how to induce sustained ART-free HIV suppression. How?: Review of 14 treatment interruption studies involving more than 700 participants. Post-treatment controllers were defined as individuals who remained off ART for ≥24 weeks and maintained viral loads ≤400 copies/mL for at least two-thirds of the time points The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study Golnaz Namazi, Jesse M. Fajnzylber, Evgenia Aga, et al. Results: 67 post-treatment controllers were identified - More likely if treatment started during early/acute HIV infection Maintenance of virological suppression: - After 1 year: 75% - After 5 years: 22% Nearly half had viral load peaks >1000 copies Only 50-60% maintained viral suppression for ≥90% of the time Contrasting Timing of Virological Relapse After Discontinuation of Tenofovir or Entecavir in Hepatitis B e Antigen–Negative Patients Christoph Höner zu Siederdissen, Aric Josun Hui, Wattana Sukeepaisarnjaroen, et al. What?: Analysis of which factors influence timing of virological relapse after cessation of treatment for chronic hepatitis B Why?: This has not previously been well studied, especially in people with eAg negative infection How?: Data from 220 people were derived from a randomised trial of a therapeutic vaccine for chronic hepatitis B. Inclusion criteria included: - on tenofovir or entecavir for at least 2 years - eAg negative and eAb positive for at least 1 year - ALT within normal range and HBV VL <40IU/mL for at least 1 year Contrasting Timing of Virological Relapse After Discontinuation of Tenofovir or Entecavir in Hepatitis B e Antigen–Negative Patients Christoph Höner zu Siederdissen, Aric Josun Hui, Wattana Sukeepaisarnjaroen, et al. Results: Type of antiviral was the only factor found to significantly influenced early (0-12 weeks) vs late (16-24 weeks) relapse - Held true for cut-offs of both HBV VL >2000 and >200 Early relapse was associated with greater falls in surface antigen levels - ?higher chance of sAg loss Reduced Incidence of Hepatocellular Carcinoma in Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis B Treated With Tenofovir Mindie H. Nguyen, Hwai-I Yang, An Le, et al. What?: Examination of the effect of tenofovir disoproxil on the incidence of hepatocellular carcinoma in an Asian population with chronic hepatitis B. Why?: There has been no study comparing HCC incidence in CHB patients treated with TDF with matched untreated patients with and without cirrhosis. Most available data examines treatment with entecavir. How?: Retrospective cohort study of 6914 patients with CHB in the USA and Taiwan. - 774 treated with TDF and 6140 received no treatment ‘Propensity score matching’ was used to adjust for higher baseline ALT and cirrhosis rates in the treated cohort Reduced Incidence of Hepatocellular Carcinoma in Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis B Treated With Tenofovir Mindie H. Nguyen, Hwai-I Yang, An Le, et al. Results: With cirrhosis Without cirrhosis Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa John Bradley, Sian Floyd, Estelle Piwowar-Manning, et al. What?: Measure the association between the HIV and HSV2 infections at the individual level, and also in an ecological analysis at the community level Why?: HIV and HSV2 are strongly associated, although mechanisms are not fully understood; and the association has not been well studied at the community level. How?: Analysis of baseline data from the 38,691 adults enrolled in the HPTN 071 (PopART) study in South Africa and Zambia - random sample of 18-44 year olds from the general population - HIV test - 4th generation Ag/Ab assay - HSV2 test - IgG serology Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa John Bradley, Sian Floyd, Estelle Piwowar-Manning, et al. Results: HIV infection was significantly more likely in HSV2-infected individuals - OR 6.66 among women - OR 6.57 among men Strong linear relationship between HIV and HSV2 prevalence at the community level ( p < .001). Critical Appraisal Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions: a Randomized Placebo-Controlled Trial Nicholas Van Wagoner, Kenneth Fife, Peter A. Leone, et al Background What does this study add to the existing literature? There is a clear need for new therapeutic options for HSV2 given its: - high prevalence (11% worldwide, approximately 417 million adults affected) - established link with subsequent HIV acquisition - often overlooked psychological effects - less than ideal current treatment options ● oral antivirals do not completely prevent recurrences or viral shedding ● chronic daily therapy has cost implications and requires daily adherence An effective therapeutic vaccine is an attractive option due to its novel mechanism of action and potential for improved adherence The primary objective of this study was to compare the rate of viral shedding at baseline with the shedding rate immediately after completion of 3-dose regimens of 6 differing dose combinations (antigen/adjuvant). Method What is the vaccine (GEN-003) and how was it given? ‘First-in-class’ T cell activating therapeutic vaccine - Antigens: glycoprotein D and infected cell protein 4 - Adjuvant: saponin derived “Matrix-M2” Antigen/adjuvant doses, all in 0.5mL: - 30/25, 30/50, 30/75, 60/25, 60/50 or 60/75 microg Placebo was 0.5mL of normal saline Subjects received 3 doses of their assigned treatment at 21 (±1) day intervals by via intramuscular injection Study staff were blinded to treatment assignment Method How did they test for viral shedding? Twice daily self-collected anogenital swabs for 28 days, tested with HSV2 PCR - at baseline (before any vaccination); and - immediately after the final dose of vaccine; and - 6 months post vaccination; and - 12 months post vaccination The presence/absence of genital lesions was self-recorded for the same times For first recurrence of genital herpes, subjects were instructed to return to the clinic for swab collection. Subjects were not permitted to take daily suppressive antiviral medication. Episodic valaciclovir could be used outside of swab collection periods. Method Who was included and excluded? Inclusion criteria: - aged 18–50 years old - diagnosis of genital HSV-2 infection for >1 year diagnosed either by: - Western blot for HSV-2 antibody; or - Positive (PCR) or viral culture from genital skin or mucous membrane; or - A compatible clinical history
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