High specific immune response to a bivalent anti-HPV vaccine in HIV-1-infected men in São Paulo, Brazil.

INTRODUCTION: Infection with Human papillomavirus (HPV) has been reported as one of the most prevalent agent sexually transmitted diseases, but its true prevalence in men is not precisely known, mainly due to the near absence of symptoms. Moreover, few studies evaluating the post-vaccination immune response have been performed to date in men, hence the hypotheses tested in this study can be important to enable a better understanding of both the immunopathogenesis and the response to vaccination in HIV-infected patients, and to help in the elaboration of strategies of vaccination against HPV in the HIV-infected population. OBJECTIVES: To analyze the specific response to antigens of HPV vaccine in HIV-infected men. METHODS: A total of 25 HIV-infected male patients who met the inclusion criteria during the data collection period were vaccinated; however, six (30%) had anti-HPV at baseline, and were not considered further in the analysis. Therefore, 19 HIV-infected individuals were included in the study, along with five healthy, HPV-seronegative controls. RESULTS: Patients infected with HIV-1 were subdivided into two groups, A and B, according to their T CD4 cells count at the time of vaccination, namely: Group A: CD4>500; Group B: CD4<500. The proportion of seroconversion after immunization with three doses of a bivalent anti-HPV vaccine was 92%. CONCLUSION: HIV-infected patients as well as HIV negative controls responded to anti-HPV vaccination, regardless of their T CD4 cells count and HIV plasma viral load. These results demonstrate that anti-HPV immunization in HIV-infected males is effective and should be encouraged, thus helping to decrease the risk of infection, mortality and morbidity of diseases associated with HPV in men.

Human papillomavirus infection in oral fluids of HIV-1-positive men: prevalence and risk factors.

Human papillomavirus is one of the most common sexually transmitted diseases worldwide. The natural history of oral HPV infection is unclear, and its risk factors have not been explored. Immunocompromised individuals, as exemplified by HIV patients, are at high risk for HPV-related diseases. The mean of this study is to determine the prevalence of HPV in the oral tract of HIV-1-positive male subjects and its association with risk factors. A total of 283 oral wash samples from HIV-1-positive men were tested. The oral fluid samples were used for DNA extraction and conventional PCR amplification; HPV genotyping was performed by hybridization. HPV genotyping revealed that nine samples (3.5%) were positive for HPV DNA; the major high-risk HPV types identified were 51 and 66. Worldwide studies have shown a variable prevalence of oral HPV. The diversity of genotypes and the high prevalence of multiple infections in HIV-infected subjects can be better explained by the effects of HIV-induced immunosuppression. The most important risk factors are unprotected sexual intercourse, but other factors for this infection have been described elsewhere including smoking, age and HIV-positive serostatus. In this study, smoking was the most important risk factor for acquiring oral HPV in HIV-1-infected subjects in Brazil.

The Th1-th2 profile in immune responses to Human papillomavirus (HPV) in vitro in men from the city of São Paulo, Brazil / Perfil Th1-Th2 nas respostas imunes ao Papilomavírus Humano (HPV) in vitro em homens da cidade de São Paulo, Brasil

Introduction: The cell-mediated immune response plays an important role in the control of HPV-induced cancers. Cytokines play an important function in host defense against HPV infection by modulating viral infection and polarizing the immune response towards Th1 or Th2 cells. Objective: To evaluate the specific immune response to HPV in vitro in men with and without lesions caused by HPV. Methods: We recruited 31 patients and 11 volunteers and divided them into the following four groups: 12 patients in Group A (HIV+/HPV+); 9 patients in Group B (HIV-/HPV+); 10 patients in Group C (HIV+/ HPV-); and 11 healthy subjects in Group D (HIV-/HPV-). PBMCs culture assays were performed to measure the levels of Th1/Th2/Th17 cytokines (IFN-γ, IL-2, TNF-α, IL-4, IL-10 and IL-17) in cells from patients stimulated with a quadrivalent HPV vaccine (HPV 6, 11, 16 and 18) and the E7 protein of HPV16. Results: The coinfected group A (HIV+/HPV+) showed higher levels of cytokines, especially Th2 cytokines, compared with the other study groups. The coinfected group had significantly higher levels of IL-6 and IL-10, which are Th2 cytokines, compared to the control group (HIV-/HPV-) (p<0.0001 and p<0.0001, respectively). Conclusion: This study reports a high production of cytokines in the coinfected group, suggesting strong immunomodulatory effects by HIV/HPV coinfection. However, further studies should be conducted to confirm these data. Because this group had high levels of Th2 cytokines, especially IL-6 and IL-10, these data suggest that these two cytokines may serve as biomarkers for viral persistence because HIV seropositive patients have a higher HPV persistence and may allow for the progression to more serious injuries to be monitored.

Introdução: A resposta imune celular exerce um importante papel no controle dos cânceres induzidos pela infecção por HPV. As citocinas desempenham um papel importante na defesa do hospedeiro contra a infecção pelo HPV pela modulação da infecção viral e a polarização da resposta imune para células Th1 ou Th2. Objetivo: Avaliar a resposta imune específica in vitro ao HPV em homens com e sem lesões causadas pelo HPV. Métodos: Foram recrutados 31 pacientes e 11 voluntários, divididos em quatro grupos: 12 pacientes no grupo A (HIV+/HPV+); 9 pacientes no grupo B (HIV-/HPV+); 10 pacientes no Grupo C (HIV+/HIV-); e 11 sujeitos saudáveis no grupo D (HIV-/HPV-). Uma cultura de PBMCs foi realizada para medir os níveis de citocinas Th1/ Th2/Th17 (IFN-γ, IL-2, TNF-α, IL-4, IL-10 e IL-17) de células de pacientes estimulados com a vacina quadrivalente para HPV (HPV 6, 11, 16 e 18) e a proteína E7 de HPV-16. Resultados: O grupo A coinfectado (HIV+/HIV+) apresentou altos níveis de citocinas, especialmente citocinas do perfil Th2, comparados com os demais grupos estudados. O grupo coinfectado apresentou níveis significativamente mais elevados de IL-6 e IL-10, citocinas do perfil Th2, comparados ao grupo controle (HIV-/HPV-) (p<0,0001 e p<0,0001, respectivamente). Conclusão: Este estudo reportou uma elevada produção de citocinas no grupo de coinfectados, sugerindo um forte efeito imunomodulatório pela coinfecção HIV/HPV. Entretanto, outros estudos devem ser conduzidos para confirmar estes dados. Devido este grupo apresentar altos níveis de citocinas Th2, especialmente IL-6 e IL-10, esses dados sugerem que essas duas citocinas podem servir como biomarcadores para a persistência viral, uma vez que pacientes soropositivos para HIV apresentam níveis mais altos de persistência pelo HPV e podem permitir que a progressão para lesões mais graves possa ser monitorada.

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

BACKGROUND: The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. METHODS: The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. RESULTS: A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72). CONCLUSION: Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.