Safety and Efficacy of Triple Therapy With Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors in Treatment-Naive Human Immunodeficiency Virus Type 2 Patients: Results From a 48-Week Phase 2 Study.

BACKGROUND: Integrase strand transfer inhibitor-based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. METHODS: We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. RESULTS: A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99-445). The median CD4 count was 438 cells/µL (IQR, 335-605), and the CD4/CD8 ratio was 0.8. Three patients discontinued the study. At week 48, all participants (27) had pVL <40 copies/mL. No virological failures were observed. Mean changes in CD4 count and CD4/CD8 ratio at week 48 were 95.59 cells/µL (95% confidence interval [CI], 28-163) and 0.32 (95% CI, .19 to .46). The most common drug-related adverse events were headache and nausea. One participant discontinued due to central nervous system symptoms. No serious adverse events were reported. CONCLUSIONS: DTG plus 2 NRTIs is safe and effective as first-line treatment for PWHIV-2 with a tolerability profile previously known. No virological failures were observed that suggest a high potency of DTG in HIV-2 as occurs in HIV-1. CLINICAL TRIALS REGISTRATION: M NCT03224338.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience / Infecção por SARS-CoV-2 em receptores de transplante renal: impacto clínico e outcomes - uma experiência de centro único

ABSTRACT Introduction: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. Methods: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. Results: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. Conclusion: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

RESUMO Introdução: Receptores de transplante renal são um subgrupo de doentes com maior risco de apresentar formas críticas de infecção por Síndrome Respiratória Aguda Grave pelo Coronavirus-2 (SARS-CoV-2) e piores outcomes devido ao tratamento imunossupressor. Aqui, apresentamos dados de uma coorte de um único centro de receptores de transplante renal com infecção por SARS-CoV-2. Métodos: Num estudo prospectivo, características basais, características clínicas, adaptação da terapêutica antiviral e de imunossupressão foram comparados entre doentes seguidos em ambulatório e doentes hospitalizados durante um período de um ano. Resultados: Foram analisados setenta e sete receptores de transplante renal, incluindo doentes de ambulatório e hospitalizados, com idade média de 57,7 (IIQ 49,7-64,9) anos. Vinte e oito (36,4%) foram tratados em ambulatório enquanto 49 (63,6%) doentes necessitaram de internação hospitalar. Entre os doentes hospitalizados, 18,4% foram admitidos na UTI, 49% apresentaram LRA, e 20,4% morreram. Foram realizados ajustes de imunossupressão em 95,9% dos pacientes hospitalizados, com dose de antimetabólitos ajustada em 83,7%, inibidores de mTOR em 14,3%, inibidores de calcineurina em 12,2%, e terapia com corticosteroides em 81,6%. Conclusão: Entre os pacientes hospitalizados, a optimização da terapêutica imunossupressora incluiu redução ou retirada de antimetabólito e aumento da dose de corticosteroides. A LRA ocorreu em quase metade dos pacientes e a mortalidade em pacientes hospitalizados atingiu 20%, refletindo uma maior gravidade da doença em relação à população em geral.

Arthritis in cat scratch disease: an unusual manifestation.

Cat scratch disease (CSD) is a zoonosis caused by Bartonella henselae, which is usually transmitted to humans through scratches or bites from infected cats. It is primarily a disease of children and adolescents, although it can affect individuals of any age. In approximately 10% of cases, patients can present atypical manifestations that may involve the musculoskeletal system. Herein, we report a case of a healthy 51-year-old man that developed low-grade fever and regional lymphadenopathy, followed by erythema nodosum and oligoarthritis. He had been scratched and bitten by his cat before the onset of symptoms. The diagnosis was confirmed serologically by the presence of high titers of specific IgG antibodies. Bartonella henselae was also detected in the blood of the owner's cat by PCR and DNA sequencing.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience.

INTRODUCTION: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. METHODS: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. RESULTS: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. CONCLUSION: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

COVID-19 and aging: Identifying measures of severity.

INTRODUCTION: We aimed to compare clinical features of older age group and young and middle-aged patients with COVID-19 and analyze mortality predictors. METHODS: Retrospective analysis of ongoing collection of prespecified data, on a single institution, including patients hospitalized consecutively due to COVID-19 infection, from March to June 2020. RESULTS: Of 195 patients, 56.9% were ⩾65 years (older age group). Older age group had multimorbidity (p < 0.001). At admission Early Warning Score-2 (p < 0.001), C-reactive protein, D-dimer, creatinine, anemia and lymphopenia were higher in older age group, as well as median time of hospitalization (14 vs 10 days, p = 0.004). Complications were more common in older age group, but there were no significant differences in admission to intensive care. There were 18 deaths, 16 in older age group. Modified Early Warning Score at admission (odds ratio = 1.60, 95% confidence interval = 1.07-1.37, p = 0.021) and C-reactive protein >5 mg/dL (odds ratio = 2.12, 95% confidence interval = 1.13-26.26, p = 0.034) were independent predictors of inhospital mortality in older age group but not in young and middle-aged. CONCLUSION: Older age group was at higher risk for complications and inhospital mortality. Identification of specific scores of severity for this population is essential to ensure that best care is provided.

Determinants of HIV-1 Late Presentation in a Cohort of Portuguese HIV-1 Patients.

Undiagnosed HIV-1 patients still account for 25% of worldwide HIV patients. Studying late presenters (LPs) for HIV care may help to identify characteristics of such patients. The present study aims to identify factors associated with late presentation and late presentation with advanced disease based on a population of patients followed in a Portuguese hospital between 1984 and 2017. Sociodemographic and clinical data from infected patients with HIV-1 aged 18 years and older, followed in Egas Moniz Hospital, in Portugal were collected. Of the 907 patients included in this study, 68.7% were males and the median age was 37 years (interquartile range 30-47). Four hundred fifty-nine patients (50.6%) were LP and, of these, 284 patients (61.9%) were LPAD. The LP population mostly originated from Portugal and sub-Saharan Africa (64.4% and 28.8%; p = .004) and the HIV exposure category, mainly heterosexuals and men have sex with men (57.0% and 24.9%; p < .001). The stage of disease and viral load at diagnosis were significantly associated with both LP and LPAD (p < .001). Factors associated with LP in the logistic regression included age at diagnosis lower than 30 years (adjusted odds ratio [aOR] 0.34; 0.17-0.68; p = .002) and origin from sub-Saharan Africa (aOR 2.24; 1.44-3.50; p < .001). Late presentation is a major obstacle to halt the HIV epidemic. In this population, the majority of newly diagnosed HIV-infected individuals were LPs. Our results characterize vulnerable populations that should be frequently tested for HIV.

Non-Tuberculous Mycobacteria: Seven-Year Experience of a Tertiary Hospital.

INTRODUCTION: Non-tuberculous mycobacteria are ubiquitous organisms. Precise determination of infection numbers is difficult, since reporting them to public health departments is frequently not mandatory; furthermore, isolating a non-tuberculous mycobacteria does not necessarily translate into disease. The aims of this study were to ascertain non-tuberculous mycobacteria data of a tertiary hospital, determine the incidence and approach to colonization versus disease, and the incidence of predisposing comorbidities. MATERIAL AND METHODS: Retrospective study in a tertiary hospital, involving patients with positive cultural exam for non-tuberculous mycobacteria in any biological sample, from 2010 to 2017. RESULTS: A total of 125 non-tuberculous mycobacteria isolates was identified, corresponding to 96 patients. Of these, 57.4% were male (n = 54); median age was 65 years (interquartile range = [50 - 82]). From these, 60.7% (n = 57) had some degree of immunosuppression, most frequently due to malignant tumour (49.0%) or HIV infection (39.2%). It was found that 29 patients (31.0%) had structural respiratory tract changes. Colonization was defined in 65.6% of patients (n = 63). While 71.0% of non-tuberculous mycobacteria infections were pulmonary, the remaining 29.0% presented as disseminated. According to available clinical records, 60.6% (n = 20) of the presumably infected patients fulfilled American Thoracic Society diagnostic criteria for non-tuberculous mycobacteria disease. DISCUSSION: Several cases of non-tuberculous mycobacteria infection in this study presented as life-threatening, multi-systemic disease, highlighting the importance of accurate diagnosis and timely treatment. Other cases of presumed infection might instead have corresponded to colonization, possibly resulting in futile therapy. CONCLUSION: While there are diagnostic criteria for treatment of non-tuberculous mycobacteria infections, no such guidelines exist to assess colonization. One of the most challenging aspects remains the correct differentiation between colonization and early-stage infection.

Introdução: Micobactérias não-tuberculosas são organismos ubiquitários. A determinação precisa de incidência e prevalência de infecções por estes agentes é difícil, uma vez que na maioria dos países não são de declaração obrigatória e o isolamento de micobactérias não-tuberculosas não traduz obrigatoriamente a presença de doença. Os objectivos do estudo foram a avaliação dos dados epidemiológicos e abordagem de micobactérias não-tuberculosas num hospital terciário, determinar a incidência de colonização versus infecção, e a presença de comorbilidades. Material e Métodos: Estudo retrospetivo num hospital terciário envolvendo doentes com exame cultural positivo para micobactérias não-tuberculosas em qualquer amostra biológica, de 2010 a 2017. Resultados: Foram isoladas 125 micobactérias não-tuberculosas, correspondendo a 96 doentes. Destes, 57,4% era do sexo masculino (n = 54); a mediana de idade era 65 anos [50 - 82], 60,7% encontrava-se imunossuprimidos, mais frequente tumor maligno (49,0%) ou infeção por vírus da imunodeficiência humana (39,2%). Vinte e nove doentes (31,0%) apresentavam alterações estruturais crónicas da árvore traqueo-brônquica. Colonização assintomática foi identificada em 65,6% dos doentes (n = 63). Do total da amostra, 71,0% das infeções por micobactérias não-tuberculosas era pulmonar, e os restantes 29,0% disseminada. De acordo com os registos clínicos disponíveis, 60,6% (n = 20) das infeções presumidas preenchia critérios de diagnóstico da American Thoracic Society. Discussão: Foram identificados vários casos de infeção multi-sistémica grave, sublinhando a importância do diagnóstico e tratamento adequados e atempados. Paralelamente, foram também descritos casos de infeção presumida que poderão ter correspondido apenas a colonizações assintomáticas. Conclusão: Enquanto se encontram publicados critérios de diagnóstico de infeção por micobactérias não-tuberculosas, tal não acontece até à data para avaliar colonizações. Assim, um dos aspectos mais desafiantes da gestão destes casos é a correcta diferenciação entre colonização assintomática e infeção em fase inicial.

[Anaerobic Bacteria with Clinical Relevance: Morphologic and Taxonomic Classification, Distribution among Human Microbiota and Microbiologic Diagnosis]. / Bactérias Anaeróbias com Relevância Clínica: Classificação Taxonómica e Morfológica, Presença na Microbiota Humana e Diagnóstico Microbiológico.

The wide burden of anaerobic bacteria colonizing human body comprises about 90% of its total biomass. The biotic relationship between humans and its microbiota sets reciprocal benefits, albeit with pathogenic potencial for the human being in particular dysbiosis situations. Infections adjacent to or originating from the skin or mucous membranes of the intestinal, genitourinary and upper respiratory tracts are often polymicrobial in nature, whereby should anaerobes be invariably included in the etiological differential diagnosis of these conditions. Gram negative bacilli such as Bacteroides fragilis group, Fusobacterium spp., Porphyromonas spp., Prevotella spp. and Gram positive cocci such as Peptostreptococcus spp. stand out for their high virulence and frequence of isolation in suppurative infections and abcesses with metastatic or contiguous relation to human microbiota. The fastidious nature of anaerobic bacteria, especially of less aerotolerant species, compels to particular techniques of sample collection, transport and cultural isolation that challenge clinicians and microbiologists for a full efficient practice. Such requirements bring on a poor identification of anaerobic bacteria in the clinical practice and undervaluation of its aetiopathogenic potential amongst common polymicrobial infections. An approach over microbial flora's composition in the different human anatomical sites is a primary goal of the present article. Clinicians are intended to recognize the variability and proportion of likely involved anaerobic microorganisms in certain infectious processes related to human microbiota, in order to optimize samples processing and the establishment of an appropriate empirical antibiotic therapy, mindful of anaerobic coverage and according to known susceptibility profiles.

A carga de bactérias anaeróbias que colonizam o organismo humano é vasta, correspondendo a cerca de 90% da biomassa humana. A relação biótica entre o ser humano e a sua microbiota configura benefícios recíprocos, embora com potencial patogénico para o Homem em situações de disbiose. Infeções com ponto de partida ou em contiguidade com a pele ou mucosas do trato intestinal, genitourinário ou respiratório alto são frequentemente polimicrobianas, devendo as bactérias anaeróbias ser invariavelmente contempladas no diagnóstico diferencial etiológico destas situações. Bacilos Gram negativo tais como Bacteroides grupo-fragilis, Fusobacterium spp., Porphyromonas spp., Prevotella spp. e cocos Gram positivo tais como Peptostreptococcus spp. destacam-se pelo seu elevado potencial de virulência e alta prevalência de isolamento em infeções supurativas e/ou abcedadas em relação contígua ou metastática com a microbiota humana. A natureza fastidiosa das bactérias anaeróbias, em especial das espécies menos aerotolerantes, condiciona particularidades nas técnicas de colheita, transporte e isolamento cultural que desafiam os clínicos e microbiologistas. Estas exigências contribuem para uma subidentificação das bactérias anaeróbias, subdiagnóstico na prática clínica e subvalorização do seupotencial etiopatogénico em focos de infeção habitualmente polimicrobianos. Conhecer a composição da flora microbiana nos diferentes locais anatómicos é objetivo primário do presente artigo. Pretende-se que os clínicos reconheçam a variabilidade e proporção dosprováveis microorganismos anaeróbios implicados em determinados processos infeciosos relacionados com a microbiota humana, com vista à optimização do processamento laboratorial de amostras e à instituição de uma antibioterapia empírica apropriada, atenta à cobertura de anaeróbios e de acordo com perfis de susceptibilidade conhecidos.

Acute Pyelonephritis with Bacteremia Caused by Enterococcus hirae: A Rare Infection in Humans.

Enterococci are one of the usual residents of the microflora in humans. In the last decade this genus has been reported as the third most common cause of bacteremia. We present the case of a 78-year-old female who was admitted to the emergency room because of nausea, lipothymia, and weakness. She was diagnosed with a pyelonephritis with bacteremia, with the isolation in blood and urine cultures of Escherichia coli and Enterococcus hirae. This last microorganism is a rarely isolated pathogen in humans. Currently it is estimated to represent 1-3% of all enterococcal species isolated in clinical practice.

The impact of tenofovir disoproxil fumarate on kidney function: four-year data from the HIV-infected outpatient cohort.

INTRODUCTION: With improvements in survival and disease progression in the era of combined antiretroviral therapy, complications such as kidney disease are becoming increasingly prevalent in HIV-infected patients. Tenofovir disoproxil fumarate (TDF) has been associated with nephrotoxicity, including decline in glomerular filtration rate, proximal tubular damage and acute kidney injury. OBJECTIVE: Characterize kidney safety of TDF-containing antiretroviral treatment (ART) regimens in HIV-infected patients. METHODS: Non-controlled, observational, retrospective study was based on the clinical files registry of HIV patients who started TDF between January and December 2008. We assessed outpatients followed at a single Portuguese center. Demographic, clinical, virological and immunological data at baseline were collected. Serum creatinine, estimated glomerular filtration rate (eGFR) and creatinine clearance (CrCL) were assessed at baseline, after six months and every year up to four years. CrCL and eGFR were calculated by Cockroft-Gault and Modification of Diet in Renal Disease equations, respectively. RESULTS: A total of 176 patients (71.6% males) with a mean age of 43 years were enrolled. Ninety-six (52%) were ART-naive patients at TDF initiation. At baseline 12.5% had hypertension, 4% diabetes, 25% chronic hepatitis C and 9% chronic hepatitis B infections; 58% had normal renal function (eGFR ≥90 ml/min/1.73 m(2)), 36% had mild (eGFR 60-89 ml/min/1.73 m(2)) renal dysfunction and 2.3% had moderate (eGFR 30-59 ml/min/1.73 m(2)) renal dysfunction at initiation of TDF. Eighty-three (47%) patients were on protease inhibitors and the remaining on NNRTIs containing regimens. During 48 months follow-up, 5% experienced moderate renal dysfunction and 1.7% severe renal dysfunction. Twenty-one (12%) patients met the definition criteria of rapid decline of renal function (annual decline of eGFR ≥3 ml/min/1.73 m(2) in two consecutive years). The development of kidney events was associated with age above 50 years, presence of comorbidities and advanced stage HIV infection (p>0.05 in univariate analysis). CONCLUSIONS: These data reveal a favourable renal safety profile of TDF, during a four-year follow-up. Screening for kidney disease markers, regular follow-up and control and prevention of risk factors for renal failure are crucial for adequate management of HIV-infected patients.

Improve screening of HCV infection by targeting high prevalence aged groups: analysis of a cohort of HCV and HIV co-infected patients.

INTRODUCTION: Hepatitis C constitutes a major public health burden. In Portugal, the prevalence is estimated at 1-1.5% (1). Of these, only 30% are presumed to be diagnosed, which reveals that most infections go unknown. The objective of this study is to identify the age-range distribution at HCV diagnosis and to identify the high-prevalence birth groups that could be targeted for screening, as a strategy to increase diagnosis and identify patients who would benefit most from treatment. METHODS: Retrospective observational study of a cohort of chronic HCV-infected and HIV co-infected patients followed at an Infectious Diseases Center, diagnosed between 1979 and 2014 (Figure 1). Hepatic fibrosis evaluation was performed by real time elastography using METAVIR score. Epidemiological, demographic, clinical, virological and therapeutic data was retrieved from clinical registries. Statistical analysis was performed using Microsoft Excel 2010®. Chi2, Student T were used for a significant p value of <0.05. RESULTS: Our study assessed a cohort of 665 patients: 442 (66.5%) HCV/HIV co-infected and 223 (33.5%) HCV monoinfected. There was a male predominance in both groups (74.9% vs 70.9%). The mean age was 47 HCV/HIV vs 49 years; Portuguese origin in 80% vs 83% and African in 14% vs 12%. The most frequently assumed transmission route was by intravenous drug use (IVDU) (81% vs 72%), followed by sexual contact (18% vs 20%). Mean age at diagnosis was 32 vs 40 years. Mean time since HCV diagnosis was 14, 6 vs 9, 6 years. Fibrosis stage evaluation by real time elastography was available for 133 (30%) and 99 (44.4%) patients (HCV/HIV vs HCV): 16% vs 13% F1; 32% vs 33% F2; 31% vs 35% F3; 21% vs 18% F4. The peak prevalence occurred between the birth intervals of 1960-1969 and 1970-1979 for both groups, corresponding to 81% vs 66,8% (p=0.003) (Figure 1). About three quarters of all patients (76%) were born between the year of 1960 and 1979, with a prevalence of 70% of IVDU. CONCLUSIONS: In our cohort we identify a high risk population for chronically HCV infection, which comprises people born between 1960 and 1979, findings common to those with mono or HIV co-infection. This finding is concordant with the epidemic of IVDU in Portugal around 1980-1990. These patients should be screened for diagnosis in order to be treated and to prevent further disease progression.

Risk of liver decompensation assessed in HIV/HCV co-infected individuals with advanced liver fibrosis: a faster countdown experience.

INTRODUCTION: Cirrhosis secondary to HCV infection is expected to peak in the next decade, particularly in the HIV co-infected subgroup and has become a leading cause of morbidity among these individuals. Efforts must be done to estimate the risk of liver decompensation (LD) in the short term, in order to define the appropriate time for HCV treatment. MATERIALS AND METHODS: Retrospective observational cohort study aimed to assess the risk of LD among a group of HIV/HCV co-infected patients diagnosed in the past 23 years in a central hospital of Lisbon. INCLUSION CRITERIA: (1) advanced liver fibrosis ≥F3; (2) HCV treatment naïve or without sustained virologic response (SVR). Patients had a one to five years period of follow-up. Multiple linear regression, Mann-Whitney and Kendall were the statistical tests performed. RESULTS: From 444 HIV/HCV co-infections, 66 met the inclusion criteria, with preponderance of male gender (82%), 35-45 years of age (55%), genotype 1a (52%), a mean of 13 years of co-infection and an AIDS stage documented in 65%, though the majority is under antiretroviral therapy (86%) and have TCD4+>500 µ/L (59%). Half (52%) showed evidence of steatosis, many of these (41%) presenting a history of alcoholism or overweight (BMI ≥25 Kg/m(2)). Pre-cirrhotic (F3 or F3/4) or cirrhotic (F4) stage was documented in 36 and 30 patients respectively. After staging, 28 (42%) initiated HCV treatment and SVR was achieved in 8 (29%) of those. Five (14%) pre-cirrhotic and twelve (40%) cirrhotic patients experienced at least one LD episode: 8 vs 28 cumulative events at five years and 2.8 vs 1.8 average years up to the first LD episode for pre-cirrhotic vs cirrhotic. The probability of remaining free of LD for pre-cirrhotic vs cirrhotic patients was 97% vs 78% (p≤0.01) at one year; 88% vs 65% (p≤0.001) at three years and 71% vs 44% (p≤0.001) at five years. Positive correlation was found between LD and the cirrhotic stage (vs pre-cirrhosis, p≤0.001), baseline AST ≥100 µ/L (vs <100 µ/L, p≤0.01) and platelet count <120 x 109/L (vs >120 x 109/L, p≤0.05). CONCLUSIONS: Cirrhosis accounts for a significant superior risk of LD. The time up to the first LD event differed in only one year between pre-cirrhotic and cirrhotic, standing for the importance of a rapid treatment referral in both subgroups. Modifiable risk factors that accelerate fibrosis are prevalent in HIV/HCV co-infected patients. Low platelet count, elevated AST and F4 stage predict the rapid progression to LD and the need for early HCV treatment. Large studies are required for further support of these results.

Analysis of hepatitis non-treatment causes in a cohort of HCV and HCV/HIV infected patients.

INTRODUCTION: The decision to start hepatitis C virus (HCV) treatment and its timing remains controversial. As new treatment regimens are approved, it is essential to identify patients eligible for each regimen in a timed and tailored approach. This study aims to identify the reasons to defer treatment of chronic hepatitis C infection in both HCV and HCV/HIV infected patients. MATERIALS AND METHODS: Retrospective observational study of a cohort of HCV chronically infected patients with or without HIV infection, followed in an infectious disease clinic in Lisbon. Demographic, epidemiological, clinical, immunologic and virologic data were collected. Statistical analysis was performed with Microsoft Office(®)- Excel 2012. Kolmogorov-Smirnov, t-test, Chi-square and correlation analysis were performed for a significant p value<0.05. RESULTS: The study included 669 patients, 225 patients infected with HCV (group A) and 444 patients co-infected with HCV/HIV (group B). The comparative analysis of those groups (A vs. B) showed: mean age was 49.4 years versus 46.9 (p<0.01), mean time since HCV diagnosis was 9.5 versus 14.6 years (p=0.558) both groups shared a male predominance and HCV acquisition due to intravenous drug use. Regarding genotype characterization, the predominant was 1a in both groups (p<0.01). Evaluation of IL28B polymorphism revealed CC 15.5% (A) versus 9.45% (B) (p<0.01). Group B mean TCD4 count was 585 cells/µL (mean percentage 27.1%). There was spontaneous viral clearance in 10.7% (A) versus 4.1% (B) (p<0.01). There were treated 52.0% (A) versus 32.2% (B) patients (p<0.01). For the untreated ones (107 - group A vs 270 - group B), no reason was identified for treatment deferral in 32.5% (A) versus 48.0% (B) patients. The most frequent reasons for deferring treatment were: withdrawal to follow-up (33.7%), active staging of disease (7.2%), alcohol abuse (6.0%) and advanced age (6.0%) in group A versus low TCD4 cell count (17.1%), loss to follow-up (7.5%), poor adherence (7.5%) and alcohol abuse (3.2%) in group B. CONCLUSIONS: One of the highlighted cause for treatment deferral in both mono and co-infected patients was withdrawal to follow-up. In co-infected patients, low TCD4 cell count and poor adherence, also gain prominence, suggesting that strategies to improve retention in care may be needed. Additionally, emergence of direct-acting antiviral agents is expected to reduce these determinants in starting treatment, namely reduce the impact of low TCD4 count in co-infected patients.

Evolution trends over three decades of HIV infection late diagnosis: the experience of a Portuguese cohort of 705 HIV-infected patients.

INTRODUCTION: Late HIV diagnosis is common and associated with an increased risk of clinical progression, blunted immune response on antiretroviral (ARV) therapy and higher risk of drug toxicity. Across Europe, more than a third of patients are diagnosed late and consequently delay medical care. European Consensus definition group identify as late presentation (LP) persons, presenting for care, with a CD4 count below 350 cell/mm(3) or presenting with AIDS-defining event, regardless of CD4 cell count. Additionally, advanced HIV disease (AD) is defined by a CD4 count below 200 cell/mm(3) or an AIDS defining condition in persons presenting to care. MATERIALS AND METHODS: Retrospective observational study of a cohort of 705 HIV-infected patients diagnosed between 1986 and 2014 and medically followed at an Infectious Diseases Service in Lisbon. OBJECTIVES: Evaluate LP rate evolution in the last three decades (10-year time intervals considered: 1986-1995; 1996-2005; 2006-2014); compare clinic, immunologic, virologic and therapeutic response over time. Identify main reasons responsible for late HIV diagnosis in order to promote optimized intervention strategies. SPSS version 20.0 was used for statistical analysis. RESULTS: Study included 705 patients HIV diagnosed during 3 time intervals: group A n=82 [1986-1995]; group B n=332 [1996-2005]; group C n=291 [2006-2014]. Demographic and epidemiological characterization revealed (A vs B vs C): male predominance of 79% vs 66% vs 66%; mean age at diagnosis 30 vs 36 vs 42 years; Portugal (82% vs 70% vs 58%) and Africa (13% vs 23% vs 29%) as the main places of birth; transmission by heterosexual contact in 21% vs 47% vs 62%, MSM in 21% vs 15% vs 23% and IVDU in 57% vs 35% vs 13%. Mean CD4 at diagnosis was 362 vs 344 vs 377 cell/mm(3). Considering the time intervals, LP was found in 52% vs 56% vs 52% of patients and AD in 31% vs 38% vs 35%, respectively. At first health care encounter, 46% vs 43% vs 39% of individuals presented with AIDS. Over follow up, the vast majority initiated ARV (95% vs 98% vs 84%) and mean CD4 at that time was 254 vs 282 vs 250 cell/mm(3). The last immunologic and virologic determination available registered mean CD4 of 657 vs 644 vs 584 cell/mm(3) and undetectable HIV plasma RNA in 92% vs 84% vs 82% of treated patients. CONCLUSIONS: This study evidenced a maintained LP rate, slightly above 50% in each of the three analyzed last decades, and one-third of patients presented AD at HIV diagnosis. At initial health care contact, nearly 40% of individuals met AIDS clinical or immunological criteria.

Durability of first antiretroviral treatment in HIV chronically infected patients: why change and what are the outcomes?

INTRODUCTION: First antiretroviral therapy (ART) is often switched to simpler, more potent or better tolerated regimens (1, 2). Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. MATERIALS AND METHODS: Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV-1 and 2 infections, evaluate factors influencing ART change, second-line ART and consequent virologic and immunologic responses. Patients had follow-ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20). RESULTS: Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV-1 infection (n=158). The mean age was 43.9 years (standard deviation±14.3), with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV-1 patients (50%) followed by lopinavir/r (22%). In HIV-2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5%) followed by therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann-Whitney, Phi coefficient -0.161) and associated with the appearance of adverse reactions (p=0.04, Chi-square). Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann-Whitney). Patients started on ART before the year 2010 reduced the probability of inferior ART duration by 25.8%. After second-line ART regimens, TCD4+ counts>500 cell/µL were increased by 38% and favourable virologic outcome achieved in 84%. CONCLUSIONS: Adverse reactions were the main cause for ART switching, supporting a cautious approach when initiating regimens, particularly in older patients. All ART naive patients who changed initial therapy had favourable immunological and virologic responses.