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.

The impact of integrase inhibitors on steatosis and fibrosis biomarkers in persons with HIV naïve to antiretroviral therapy.

BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among persons with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs on variation of liver steatosis and fibrosis in the ART-naïve person with HIV, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). METHODS: We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. RESULTS: 99 patients were included in our study. 82% were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p = 0.114). We observed a significant decrease in FIB-4 (p = 0.007) and NFS (p = 0.002). BARD score showed a significant increase (p = 0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (ß= -0.08, 95% CI [-0.16 to -0.00], p = 0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. CONCLUSION: INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the "return-to-health effect" observed with ART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in ART-naïve persons with HIV, possibly due to their effect on viral suppression.

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.

Real-World Characterization of the Portuguese Population Living with HIV who Initiated Raltegravir Based-Regimens: The REALITY Study.

INTRODUCTION: Although raltegravir has been available since 2007, data are lacking on the Portuguese population living with HIV who initiated this antiretroviral therapy. Hence, this study aimed to characterize the patients who initiated raltegravir-based regimens between January 2015 and December 2017, on sociodemographics, clinical features, and treatment satisfaction. MATERIAL AND METHODS: Observational, retrospective, multicentre study conducted at 11 reference sites. Sociodemographic and clinical data were collected retrospectively from hospital medical records. For participants continuing raltegravir at study inclusion, the HIV Treatment Satisfaction Questionnaire was administered to assess satisfaction with raltegravir-based therapy. Descriptive statistics were performed. Treatment-naïve and treatment-experienced subgroups were compared for demographic and clinical variables. RESULTS: A total of 302 patients were included; mostly men (69.5%) with a mean age of 49 years old. Approximately half of the patients had at least one non-AIDS-related comorbidity at baseline (53.3%), such as hypercholesterolemia, arterial hypertension, diabetes mellitus, and depression. Moreover, 52.3% were treatment-experienced patients with up to two treatments prior to raltegravir. Across the study time points, there was a reduction in the viral load and improvement in CD4 counts in both the treatment-naïve and treatment-experienced subgroups. Continuing users of raltegravir reported high treatment satisfaction (55.4 ± 7.2 points). CONCLUSION: Raltegravir-based regimens seem like a valid therapeutic option in heterogeneous populations of HIV-infected patients, in patients with previous ART experience and as part of first-line therapeutic options alongside with the latest generation of drugs from its class.

Introdução: Apesar de o raltegravir estar disponível desde 2007, os dados na população portuguesa com VIH que iniciou esta terapêutica antirretroviral são escassos. Deste modo, este estudo teve por objetivo caracterizar os doentes que iniciaram um regime terapêutico baseado em raltegravir entre janeiro de 2015 e dezembro de 2017, relativamente a dados sociodemográficos, características clínicas e satisfação com o tratamento. Material e Métodos: Estudo observacional, retrospetivo, multicêntrico conduzido em 11 centros de referência. Os dados sociodemográficos e clínicos foram recolhidos retrospetivamente nos processos clínicos. Os participantes que continuaram o regime com raltegravir após a inclusão no estudo preencheram o HIV Treatment Satisfaction Questionnaire para avaliar a satisfação com a terapêutica. Foram efetuadas análises de estatística descritiva e comparações para as variáveis sociodemográficas e clínicas nos subgrupos de doentes naïve de tratamento e de doentes com experiência terapêutica. Resultados: Foram incluídos 302 doentes, maioritariamente do sexo masculino (69,5%) com idade média de 49 anos. Aproximadamente metade dos doentes tinha pelo menos uma comorbilidade não relacionada com SIDA no início do estudo (53,3%), tais como hipercolesterolemia, hipertensão arterial, diabetes mellitus ou depressão. Adicionalmente, 52,3% eram doentes com experiência terapêutica com até dois tratamentos anteriores ao raltegravir. Ao longo do estudo verificou-se uma redução na carga viral e uma melhoria nas contagens de CD4 em ambos os subgrupos de doentes (doentes naïve de tratamento e doentes com experiência terapêutica). Os doentes com uso continuado de raltegravir reportaram uma elevada satisfação com o tratamento (55,4 ± 7,2 pontos). Conclusão: Os regimes terapêuticos baseados em raltegravir parecem ser uma opção terapêutica válida em populações heterogéneas de doentes infetados com VIH, em doentes com experiência em ART e como tratamento de primeira linha, em paralelo com outras terapêuticas de última geração.

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group).

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.

The Influence of Antiretroviral Therapy on Hepatitis C Virus Viral Load and Liver Fibrosis in Human Immunodeficiency Virus-Coinfected Patients: An Observational Study.

BACKGROUND: The role of antiretroviral therapy (ART) for Hepatitis C viral load (HCV-VL) and liver fibrosis is poorly understood. This study aimed at evaluating the influence of ART on HCV-VL and liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We conducted a retrospective cohort study of HIV/HCV-coinfected patients followed at a tertiary university hospital. RESULTS: In total, 143 patients were included. In 61 patients, ART initiation was accompanied by an increase in HCV-VL and a decrease in HIV viral load (HIV-VL), whereas ART suspension led to a decrease in HCV-VL and an increase in HIV-VL. Among the 55 HIV-suppressed patients who switched to a raltegravir (RAL)-containing regimen, median HCV-VL levels decreased significantly, while switching to a rilpivirine-containing regimen did not yield a significant reduction. DISCUSSION: If the -treatment of chronic hepatitis starts before ART, ART initiation should be delayed as much as possible. If ART has been started, it is advisable to wait 1 year before initiating chronic hepatitis treatment. RAL as the third agent in an ART regimen could be beneficial in HIV/HCV-coinfected patients, in comparison to other antiretroviral drugs. CONCLUSION: The start and the suspension of ART significantly interferes with HCV-VL in HIV/HCV-coinfected patients.

Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study.

OBJECTIVE: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. METHODS: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. RESULTS: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005). CONCLUSIONS: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.

Metabolically Healthy or Metabolically Unhealthy Obese HIV-Infected Patients: Mostly a Matter of Age?

Background: Life expectancy of HIV-infected patients has increased with antiretroviral treatment (ART). Chronic diseases associated with aging, including metabolic and cardiovascular diseases are becoming more prevalent in this population. We aimed to evaluate the association of obesity and aging with cardiometabolic comorbidities and metabolic health status among patients with HIV infection. Methods: We evaluated 580 HIV-1 infected patients (71.7% male, mean age of 47.7 ± 11.5 years). We analyzed the association of age and obesity (defined by and by central obesity) with gender, duration of HIV infection, and ART, anthropometric parameters, cardiometabolic comorbidities, Framingham risk score (FRS), blood pressure, lipid profile, uric acid, liver biochemical tests, and glycemic profile. Furthermore, we analyzed the above-mentioned associations according to the category and central obesity into the metabolically healthy (MH) and unhealthy (MUH) categories. To evaluate the association of anthropometric parameters with cardiometabolic comorbidities, we performed unadjusted and adjusted logistic regression models. Results: The prevalence of excessive weight and cardiometabolic comorbidities increased with age. Patients with normal weight were younger and there was a higher proportion of female patients in the obesity group. The prevalence of hypertension and metabolic syndrome were higher among patients who were overweight or with obesity. The FRS was higher among patients with obesity. The proportion of MUH patients was higher among patients with excessive weight and central obesity. MUH patients had more cardiometabolic comorbidities and a higher FRS. In the normal weight group, MUH patients were older, and in the obesity group they were more likely to be male. The anthropometric parameter most associated with metabolic syndrome was waist circumference and that most associated with hypertension was waist-to-height ratio. The anthropometric parameter most associated with diabetes and FRS was waist-to-hip ratio. Conclusion: Patients with HIV present a high prevalence of obesity and related comorbidities. Ageing significantly contributes to metabolic dysfunction in this population. The proportion of MUH patients is higher among groups with excessive weight and central obesity, with those patients presenting a higher cardiovascular risk. Our results highlight the importance of evaluating and addressing obesity in patients with HIV, as well as metabolic comorbidities and cardiovascular risk.

Routine CD4 monitoring in HIV patients with viral suppression: Is it really necessary? A Portuguese cohort.

PURPOSE: CD4 cell-count has been regarded as the key surrogate marker for prognostic staging and therapeutic monitoring of HIV-infected individuals. Our purpose was to assess the probability of maintaining a CD4 count >200 cells/µL in patients with continuous viral suppression and CD4 cell counts >200 cells/µL. METHODS: Retrospective cohort study of HIV-infected patients, treatment naïve, who started antiretroviral therapy between 2007 and 2011. We estimated the probability of maintaining CD4 counts >200 cells/µL during continuous viral suppression using the Kaplan-Meier method. The hazard ratios of a CD4 count <200 cells/µL were estimated and compared using Cox proportional hazards regression. RESULTS: 401 patients were included: 70.1% men; median age 37 years; 98.8% HIV-1 infected. The median duration of continuous viral suppression with CD4 counts >200 cells/µL was 40.5 months. Ninety-three percent of patients maintained CD4 counts ≥200 cells/µL during the period of continuous viral suppression. Compared with those with an initial CD4 count ≥350 cells/µL, patients with initial CD4 count <300 cells/µL had a significantly higher risk of a CD4 count <200 cells/µL. Patients with viral suppression and CD4 counts ≥350 cells/µL had a 97.1% probability of maintaining CD4 cell counts ≥200 cells/µL for 48 months. CONCLUSIONS: The probability of a CD4 count <200 cells/µL in an HIV-infected patient with viral suppression and CD4 ≥350 cells/µL was very low. These data suggests less frequent monitoring of CD4 counts in these patients.

Prozone-like phenomenon in travellers with fatal malaria: report of two cases.

Malaria diagnosis remains a concern in non-endemic countries, with rapid diagnosis being crucial to improve patients' outcome. Rapid diagnostic tests have high sensitivity but they also have flaws and false-negative results that might jeopardize malaria diagnosis. Some false-negative results might relate to a prozone-like effect. The authors describe two patients with false-negative rapid diagnostic tests in which a prozone-like effect might have been involved. The authors highlight that these tests should not be used without accompanying light microscopy observation of blood films and discuss potential benefits of using rapid diagnostic tests with more than one specific antigen for Plasmodium falciparum.

Characterization of HIV-1 subtypes in a Portuguese cohort.

INTRODUCTION: Distribution of HIV-1 subtypes is variable around the world, with the most common subtype in western Europe being subtype B. The aim our study was to describe the prevalence of different HIV-1 subtypes in newly diagnosed patients and identify demographic and epidemiological characteristics related with different subtypes. MATERIALS AND METHODS: Retrospective single-centre study of patients newly diagnosed with HIV-1 infection between 2006 and 2012. Epidemiological data was gathered and genotyping was performed in each patient identified. Demographic and epidemiological characteristics were compared between patients with subtype B and other subtypes. Continuous variables were summarized by mean and standard deviation whereas categorical variables were presented as proportions. Comparison of groups was performed using the Chi square, Fisher exact test and Student T test. Statistical significance was assumed when p<0.05. RESULTS: In the period of the study, 624 patients newly diagnosed with HIV-1 infection were submitted to genotypic testing but information about subtype was available only for 592 patients. General characteristics of the patients are summarized in Table 1. The distribution of the identified subtypes was the following: 286 (48.3%) patients had subtype B, 157 (26.5%) had subtype G, 54 (9.1%) had subtype C, 36 (6.1%) had subtype A, 32 (5.4%) had subtype F and 25 (4.2%) had CRF's. Patients with subtype B were more commonly male (p=0.001) and younger (p<0.0001) than those with subtypes other than B. Subtype B was more common in MSM patients, while non-B subtypes were more common in heterosexual patients and in injecting drug users (p=0.001). CD4-cell count, viral load and AIDS at presentation were not significantly different between subtypes. Resistance associated mutations were significantly more common in patients with non-B subtypes (15.4% vs 9.8%; p=0.048). CONCLUSIONS: The most commonly identified subtype was B in accordance with previous reports from other western European countries. However, in our cohort the proportion of non-B subtypes is higher than that reported for other European countries, probably reflecting the influence of strong bonds with Portuguese speaking African countries. Knowledge about HIV subtypes distribution may help understanding transmission dynamics and can be an important tool in the design of preventive measures.

Prevention of mother-to-child transmission: experience of a Portuguese centre.

INTRODUCTION: HIV infection during pregnancy still raises controversial issues. Combined antiretroviral therapy (cART) has been successful in reducing mother-to-child transmission (MTCT). Routine screening in pregnancy and in pre-conception consultation proved to be one of the best methods able to get this treatment on time. We review our experience with pregnant patients with HIV infection. MATERIALS AND METHODS: Retrospective and descriptive study. Data obtained from HIV-infected pregnant women from 1999 to 2012 with delivery and subsequent infectious diseases follow-up at our hospital. RESULTS: We evaluated 136 patients (169 pregnancies), with a total of 147 living newborns (2 twin pregnancies) and 1 stillbirth. Median age at pregnancy was 30 (SD 5.7) years. Four patients were HIV-2 infected and one HIV-1+2 infected. 26 (19.1%) women were HCV co-infected and 6 (4.4%) HBV co-infected; 1 patient has HCV and HBV co-infection. Sexual risk for HIV acquisition was determined in 102 (75%) patients and 31 (22.8%) were intravenous drug users. 33/136 (24.2%) women were diagnosed on routine screening in pregnancy, 4 during delivery and 2 immediately after delivery. 36 (26.4%) patients had an AIDS-defining entity before pregnancy and no new opportunistic infections were diagnosed. ART was used in 157 (92.9%) pregnancies and 15 (9.5%) of them were treated only with NRTIs. At the time of delivery 86/144 (59.7%) patients had undetectable viral load (VL) (25 patients without VL determined), 91.7% of those on ART. 119 (70.4%) had a TCD4 cell count above 200 cells/mm(3). MTCT occurred in 3/147 cases (2%): in one mother HIV-1 infection was diagnosed three weeks before delivery, other immediately after delivery and the third woman started cART (2NRTI+1PI/r) in the second trimester of pregnancy, always adherent and without secondary effects, VL at delivery was 50 copies/mL and elective C-section was performed. CONCLUSIONS: The fact that 24% of patients were diagnosed during pregnancy shows the importance of routine screening to all pregnant women. MTCT occurred in three children, but only one was administered cART for prevention.

Primary drug resistance at diagnosis of HIV-1 infection: a Portuguese cohort.

INTRODUCTION: Presence of viral mutations conferring resistance to antiretroviral drugs has potential impact on success of antiretroviral therapy (ART). The aim of this study was to describe the prevalence of resistance-associated mutations in HIV-infected patients without prior ART in a Portuguese cohort. MATERIALS AND METHODS: Retrospective single-centre study of patients newly diagnosed with HIV-1 infection between 2006 and 2012. Resistance genotyping was obtained with HIV TRUGENE(®) and Viroseq(®) tests and the analysis of drug resistance was based on the Stanford University HIV Drug Resistance Database. Epidemiological data was also gathered. Continuous variables were summarized by mean and standard deviation, whereas categorical variables were presented as proportions. Comparison of proportions was performed with Chi square and Fisher exact test while means were compared with Student test. Statistical significance was assumed when p<0.05. Statistical analysis was performed with SPSS 21.0(®). RESULTS: Resistance testing was performed in 624 patients. General characteristics of the patients are summarized in Table 1. Mutations were found in 291 (46.6%) patients but resistance-associated mutations were present in 79 (12.7%) patients. Resistances to different drug classes were the following: NNRTIs-resistance in 42 (6.7%) patients; NRTIs-resistance in 19 (3.0%) patients; PIs-resistance in 30 (4.8%) patients. Only 10 (1.6%) patients presented simultaneous resistance-associated mutations to more than one class of drugs. There were no statistical significant differences between the years at which HIV-1 was diagnosed. Also no significant difference in the distribution of the parameters age, sex, CD4-cell count, and viral load, between groups with and without resistance was identified. Resistance-associated mutations were significantly more common in patients with non-B HIV-1 subtypes (15.4% vs 9.8%; p=0.048) and in those presenting with AIDS (18.2% vs 11.1%; p=0.03). CONCLUSIONS: Prevalence of resistance-associated mutations identified in this study was similar to those reported in similar studies from Western Europe. Knowledge about the epidemiology of primary resistance in our country is important in order to improve HIV care.

Peginterferon alfa-2a plus ribavirin for HIV-HCV genotype 1 coinfected patients: a randomized international trial.

BACKGROUND: The safety and efficacy of weight-based ribavirin (RBV) dosing regimens in patients with HIV-HCV coinfection has not been demonstrated in randomized clinical trials. OBJECTIVE: This randomized, double-blind, international, parallel-group study in specialist outpatient clinics in the United States, Spain, and Portugal compares the efficacy and safety of 2 RBV dose regimens (800 mg/day and 1000/1200 mg/day) combined with peginterferon alfa-2a (40KD) in patients with HIV-HCV (genotype 1) coinfection. METHODS: Patients with HIV-HCV coinfection, quantifiable HCV RNA in serum, HCV genotype-1 infection, compensated liver disease, and stable HIV disease (CD4+ count ≥100 cells/µL) with or without ongoing antiretroviral therapy were randomized to 48 weeks' treatment with RBV at standard dose (800 mg/day) or weight-based dose (1000 mg/day for patients weighing <75 kg; 1200 mg/day for patients weighing ≥75 kg) in combination with peginterferon alfa-2a (40KD) 180 µg once a week. Planned enrollment was 400 patients with ≥100 non-Latino African Americans. The primary endpoint was sustained virological response (SVR) (undetectable HCV RNA [<20 IU/mL] at the end of a 24-week untreated follow-up period [week 72]). RESULTS: SVR rates were 19% (26/135) and 22% (60/275) in patients randomized to RBV 800 mg/day and 1000/1200 mg/day, respectively (odds ratio, 1.15; 95% CI, 0.68-1.93; P = .6119). In the 1000/1200 mg/day RBV dose group, the incidence of hemoglobin reductions <100 g/L and anaemia reported as an adverse event were higher versus the standard 800 mg/day RBV dose group. CONCLUSIONS: Compared with the standard RBV dose (800 mg/day), weight-based RBV dosing (1000/1200 mg/day) did not significantly increase SVR rates, but did increase the incidence of anemia in HIV-HCV (genotype 1) coinfected patients.

Ophthalmic manifestations in 18 patients with botulism diagnosed in Porto, Portugal between 1998 and 2003.

BACKGROUND: Botulism is a rare but potentially lethal disease in which ophthalmic signs and symptoms are among the very earliest manifestations. The aim of this study was to investigate the epidemiological and clinical features of botulism-infected patients admitted to a general hospital in Porto, Portugal. METHODS: We performed a retrospective chart review of all botulism patients admitted to São João Hospital between January 1998 and January 2003. We excerpted data on epidemiology, ophthalmic and non-ophthalmic manifestations, and treatment. RESULTS: We identified 18 patients in nine registered outbreaks. In two patients (11%), ophthalmic manifestations preceded systemic manifestations; in six patients (33%), ophthalmic and systemic manifestations occurred simultaneously; in ten patients (56%), systemic manifestations occurred first. Ophthalmologists had examined only seven patients and made the correct diagnosis in five. The most common ocular symptoms were blurred near vision (100%), blurred distant vision (94%), and diplopia (44%). Accommodation impairment was documented in all seven patients examined by ophthalmologists. CONCLUSIONS: Ophthalmic manifestations were among the earliest and most prominent manifestations of botulism in this series, as in earlier reports. The diagnosis should be suspected when impaired accommodation and gastrointestinal symptoms occur together.