Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Hepatitis E in a Portuguese cohort of human immunodeficiency virus positive patients: High seroprevalence but no chronic infections.

Introduction: Hepatitis E virus (HEV) infection causes zoonotic hepatitis in Europe, with a higher risk of complications in immunocompromised hosts. HEV natural history in human immunodeficiency virus (HIV) positive patients is not fully understood, and its prevalence is unknown. Objectives: To study the seroprevalence of HEV and prevalence of chronic HEV in HIV-positive patients from Porto, Portugal. Methods: We randomly selected patients from the cohort of HIV-positive patients followed in our hospital. We performed an enzyme-linked immunosorbent assay to search for immunoglobulin G for HEV. When the absorbance/cut-off was inferior to 3.5, the test was repeated, and a confirmatory test executed in that sample. For reactive tests and for immunosuppressed patients (CD4 count < 200/mm3) with nonreactive test, a polymerase chain reaction (PCR) test was also performed. Results: We included 299 patients. The mean age was 48 and 75.3% were men. Regarding HIV infection, the median follow-up time was 10 years, the acquisition was mainly heterosexual contact, and 94% were on antiretroviral therapy. Seventy-six patients (25.4%) had reactive immunoglobulin G (IgG) hepatitis E serology. Patients with a reactive test were older (statistically significant difference). Otherwise, there was no difference between groups concerning birthplace, rural residence, chronic viral hepatitis coinfection, or cirrhosis. Nadir and actual TCD4+ lymphocyte counts did not differ significantly from patients with HEV reactive and nonreactive serology. Gamma-glutamyl-transferase (GGT) was higher in patients with reactive IgG HEV. All serum HEV PCR tests were negative. Conclusions: Seroprevalence of HEV was 25.4% in HIV-positive patients. Older age and higher GGT correlated to HEV reactive IgG test. No cases of current hepatitis E were found.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

Acute HIV infection presenting as hemophagocytic syndrome with an unusual serological and virological response to ART.

BACKGROUND: HIV clinical presentation in the acute stage is variable and some of its virological and immunological aspects are not completely understood. Most cases of HIV- associated reactive hemophagocytic syndrome have been reported in patients with advanced stages of HIV and to our knowledge, there are only 8 cases in the English literature presenting during acute HIV infection, most in East Asia, being this the first case in a European patient. CASE PRESENTATION: We report a case of a European Caucasian 27- year old woman with a primary HIV- infection presenting with extremely low CD4+ T cell count who developed a haemophagocytic syndrome after starting ART and in whom we documented a very unusual serological and virological response, characterized by an impaired HIV- antibody production and a 12 month time frame to reach an undetectable viral load, despite no evidence of resistance. CONCLUSIONS: This case report apart from describing an unusual clinical presentation of an acute HIV infection as hemophagocytic syndrome provides useful information that might contribute for understanding some subtle issues in acute HIV infection, namely the dynamics of virological and immunological aspects after antiretroviral therapy initiation.

[Evolution of residual risk for HIV, HCV and HBV, from 1999 to 2010, in blood donations of the Centro Hospitalar S. João, EPE, Porto, Portugal]. / Evolução do risco residual infeccioso para o VIH, VHC e VHB, nas dádivas de sangue do Centro Hospitalar de S. João, entre os anos de 1999 e 2010.

INTRODUCTION/OBJECTIVES: Monitoring the residual risk of transfusion-transmitted viral infections is important to evaluate the improvement achieved in the blood donation safety and to adopt policies to reduce risks. The present study calculates the incidence of the key infectious diseases, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) as well as the residual risk of transfusion-transmitted viral infections, during twelve years, 1999 through 2010. Data were analyzed over 3 periods of 4 years (1999-2002, 2003-2006 and 2007-2010). The risk estimates were compared to those previously obtained for blood donations occurred between 1991 and 1998. MATERIAL AND METHODS: The study included 209 640 blood donations, from 42 634 regular, volunteers and unpaid donors. The residual risk of transfusion-transmitted infection per million donations was calculated, for each virus, through mathematical model "Incidence rate/window period", described by Schreiber et al. All donations were screened according to Portuguese legislation. In January 2001, the nucleic acid testing in minipool was implemented on all blood donations, for screening simultaneously HIV-1 and HCV ribonucleic acid (RNA) (Cobas Amplicor Ampliscreen-Roche©). This test was replaced, in January 2007, by the simultaneous screening of HBV deoxyribonucleic acid, HCV RNA and HIV-1/HIV-2 RNA, in minipool (Cobas Taqscreen MPX Test-Roche©). RESULTS: The residual risk of transmitting viral infections during the transfusion of blood components is very small and has declined over the years. After the implementation of the nucleic acid testing in minipool for the three viruses, the risk of giving blood during an infectious window period was estimated as follows: for human immunodeficiency virus, 1 in 1.67 million, for hepatitis C virus 1 in 3.33 million and for hepatitis B virus 1 in 526 000. CONCLUSIONS: During the 12 years under study, we found a decrease in residual risk for the three viruses, by a factor around five for human immunodeficiency virus and hepatitis B virus, and 32 for hepatitis C virus. If we compare the estimates previously calculated for 1991-1998 period to 2007-2010 period (over 20 years), the decrease is still more relevant with a residual risk of human immunodeficiency virus, hepatitis B virus and hepatitis C virus respectively 19-fold, 6-fold and 54-fold lower.

Introdução/Objectivo: A monitorização do risco residual infeccioso pela transfusão, é importante pois permite avaliar a melhoria alcançada na segurança das dádivas de sangue e adoptar políticas adequadas de redução dos riscos. Este estudo calcula as estimativas da taxa de incidência e do risco residual infeccioso para as infecções pelo vírus da imunodeficiência humana (VIH), vírus da hepatite B (VHB) e vírus da hepatite C (VHC), entre 1999 e 2010. Os dados foram analisados em períodos de quatro anos (1999-2002, 2003-2006 e 2007-2010) e as estimativas foram comparadas com as obtidas previamente, para dádivas ocorridas entre 1991 e 1998.Material e Métodos: O estudo incluiu 209 640 colheitas de sangue, provenientes de 42 634 dadores regulares, voluntários e não remunerados. Para o cálculo do risco residual infeccioso, utilizamos o modelo matemático taxa de incidência-período de janela, descrito por Schreiber et al. Todas as dádivas foram rastreadas de acordo com a legislação portuguesa. Em Janeiro de 2001 foi implementado, em todas as dádivas de sangue, o teste de ácidos nucleicos em minipool, para o rastreio simultâneo de ácido ribonucleico (ARN) VIH-1 e VHC (Cobas Amplicor Ampliscreen-Roche©) o qual foi substituído, em Janeiro de 2007, pelo rastreio simultâneo de ácido desoxirribonucleico VHB e de ácido ribonucleico VHC e VIH-1/VIH-2, em minipool (Cobas TaqScreen MPX Test-Roche©).Resultados: O risco residual infeccioso de uma dádiva em período de janela é muito reduzido e tem diminuído ao longo dos anos. Após a implementação de teste de ácidos nucleicos em minipool para os três vírus, a probabilidade de colhermos uma dádiva infecciosa e não detectada pelos testes de rastreio foi de 1/1,67 milhões de dádivas para o vírus da imunodeficiência humana, de 1/3,33 milhões para o vírus da hepatite C e de 1/526 000 para o vírus da hepatite B.Conclusões: Durante os 12 anos em estudo verificamos uma diminuição do risco residual infeccioso de cinco vezes para o vírus da imunodeficiência humana e vírus da hepatite B, e de 32 vezes para o vírus da hepatite C. Se compararmos o período 1991-1998 com o último período do estudo, 2007-2010, ou seja, durante 20 anos, a diminuição é relevante, verificando-se uma diminuição do risco para vírus da imunodeficiência humana, vírus da hepatite B e vírus da hepatite C, na ordem de 19, seis e 54 vezes respectivamente.