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1.
Front Public Health ; 12: 1336845, 2024.
Article in English | MEDLINE | ID: mdl-38500732

ABSTRACT

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.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Male , Humans , Adult , Homosexuality, Male , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control , Portugal/epidemiology , Europe
2.
Mol Biol Rep ; 49(11): 10347-10356, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36097125

ABSTRACT

BACKGROUND: Sickle Cell Anemia (SCA) is a genetic disease caused by the c.20 A > T mutation in HBB gene, generally characterized by sickle erythrocytes, chronic hemolytic anemia, and vaso-occlusive events. This study aimed to investigate genetic modulators of anemia severity, chronic hemolytic rate, and clinical manifestations in pediatric SCA patients from Angola, where the disease is a severe public health problem. METHODS AND RESULTS: The study was conducted on 200 SCA children living in Luanda or Caxito province. Their clinical phenotype was collected from patients' hospital records. Hematological and biochemical phenotypes were characterized in steady state condition. Twelve polymorphic regions in VCAM1, CD36 and NOS3 genes were genotyped using PCR, RFLP, and Sanger sequencing. CD36 gene promoter variants showed a significant impact on anemia severity. Particularly, the rs1413661_C allele was associated with lower hemoglobin levels, and increased number of hospitalizations and transfusions. This is the first report associating this SNP with SCA phenotypic heterogeneity. Moreover, the rs1041163_C allele in VCAM1 was associated with lower LDH levels; inversely the rs2070744_C allele in NOS3 was related with higher LDH levels and number of hospitalizations, being a risk factor for increased hemolytic rate. CONCLUSION: This study highlights, for the first time in the Angolan population, the importance of the genetic modifiers of vascular cell adhesion and nitric oxide metabolism in SCA pediatric phenotypic variability.


Subject(s)
Anemia, Sickle Cell , Hemolysis , Humans , Anemia, Sickle Cell/genetics , Erythrocytes , Alleles , Hospitalization
3.
Front Microbiol ; 13: 823208, 2022.
Article in English | MEDLINE | ID: mdl-35558119

ABSTRACT

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.

4.
Mol Biol Rep ; 47(7): 5397-5402, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32632780

ABSTRACT

The aim of this study was to explore the association between alpha-thalassemia, fetal hemoglobin, hematological indices, and clinical adverse events in Angolan sickle cell disease pediatric patients. A total of 200 sickle cell disease (SCD) children were sampled in Luanda and Caxito. A venous blood sample was collected and used for hematological analyses, fetal hemoglobin quantification, and genotyping of 3.7 kb alpha-thalassemia deletion by GAP-PCR. The frequency of the 3.7 kb alpha-thalassemia deletion in homozygosity was 12.5% and in heterozygosity was 55.0%. An increase in alpha-thalassemia frequency was observed in children older than 5 years old (11.7% vs. 13.00%). Furthermore, 3.7 kb alpha-thalassemia deletion homozygotes had a significantly higher age of the first manifestation, lower number of blood transfusions by year, higher hemoglobin, lower mean corpuscular volume, mean corpuscular hemoglobin, and lower hemolytic rate observed by a lower number of reticulocytes count. There were no differences in fetal hemoglobin between the three genotypes. Moreover, the number of stroke events, osteomyelitis, splenomegaly, splenectomy, and hepatomegaly were lower when alpha-thalassemia was co-inherited. For the first time in Angolan population, the effect of alpha-thalassemia deletion in sickle cell disease was analyzed and results reinforce that this trait influences the hematological and clinical aspects and produces a milder phenotype.


Subject(s)
Anemia, Sickle Cell/genetics , alpha-Thalassemia/genetics , Adolescent , Anemia, Sickle Cell/epidemiology , Angola/epidemiology , Child , Child, Preschool , Cohort Studies , Comorbidity , Erythrocyte Indices , Female , Fetal Hemoglobin/genetics , Genotype , Hemolysis , Heterozygote , Homozygote , Humans , Male , alpha-Thalassemia/epidemiology
5.
J Viral Hepat ; 27(7): 715-720, 2020 07.
Article in English | MEDLINE | ID: mdl-32096268

ABSTRACT

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.


Subject(s)
Antiviral Agents , Coinfection , HIV Infections , Hepatitis C, Chronic , Adult , Aged , Antiviral Agents/therapeutic use , Coinfection/drug therapy , Drug Therapy, Combination , Female , Genotype , HIV Infections/drug therapy , Hepacivirus , Hepatitis C, Chronic/drug therapy , Humans , Male , Middle Aged , Nigeria , Portugal , Quality of Life , Sofosbuvir/therapeutic use , Treatment Outcome , Young Adult
7.
Eplasty ; 16: e31, 2016.
Article in English | MEDLINE | ID: mdl-28123628

ABSTRACT

Objectives: HIV-associated lipodystrophy is a common comorbidity in HIV-infected patients, having a profound impact on every aspect of patients' lives, particularly when involving the face. Hence, it is of the utmost importance to evaluate the result of any potential therapies that may help solve HIV-associated facial lipodystrophy. The aim of this article was to evaluate the outcome of patients undergoing facial lipodystrophy correction surgery within our institution. Methods: A retrospective analysis of the clinical charts and iconographic information of patients regarding demographics, morphologic changes, surgical option, postoperative complications, results, and patient satisfaction assessed by a 1- to 10-point scale and by the Assessment of Body Change and Distress questionnaire. Results: Twenty-three patients were operated on from March 2011 to April 2015. Seventy-five percent of cases were treated with fat graft injection, whereas dermis-fat grafts were applied in 25% of patients. The former had their fat harvested more commonly from the abdomen, whereas in the latter case, the graft was harvested mostly from the inner aspect of arms. The mean volume of fat injected on each side of the face was 28.5 ± 22.7 mL. On a scale from 1 to 10, mean patient satisfaction was 7.7 ± 2.8. The Assessment of Body Change and Distress questionnaire revealed statistically significant improvements. Complications occurred in 25% of cases, the most frequent being significant reabsorption. No major complications occurred. Conclusions: Treatment of HIV-associated facial lipodystrophy with autologous fat or dermis-fat compound graft is a safe procedure with long-lasting results and unquestionable aesthetic and social benefits.

8.
BMJ Case Rep ; 20152015 Oct 29.
Article in English | MEDLINE | ID: mdl-26516245

ABSTRACT

The advent of highly active antiretroviral therapy for HIV infection dramatically changed the landscape of the disease. Ritonavir, a protease inhibitor (PI) frequently used in low doses to 'boost' the concentrations of other PIs, inhibits the cytochrome P450 3A4 isoenzyme, a common metabolic pathway to multiple drugs, so the potential for drug interactions is not negligible. A 39-year-old man with HIV-1 infection, treated with a ritonavir-boosted PI, was started on fluticasone/salmeterol inhaler and intranasal fluticasone, in 2009, in the setting of asthma and allergic rhinitis. In 2013, he presented with 1-year evolution of symptoms suggesting Cushing's syndrome, and was experiencing recurrent falls. A spine CT showed a vertical L3 fracture and thoracolumbar erosions; a bone density scan revealed severe osteoporosis. Hormonal assays were compatible with hypothalamic-pituitary-adrenal axis suppression, and iatrogenic Cushing's syndrome due to ritonavir-fluticasone interaction was considered. Fluticasone was suspended and oral corticosteroid replacement initiated, with a favourable outcome.


Subject(s)
Anti-Allergic Agents/adverse effects , Bronchodilator Agents/adverse effects , Cushing Syndrome/chemically induced , Fluticasone/adverse effects , HIV Protease Inhibitors/adverse effects , Osteoporosis/chemically induced , Ritonavir/adverse effects , Accidental Falls , Adult , Asthma/drug therapy , Cushing Syndrome/drug therapy , Drug Interactions , HIV Infections/drug therapy , Humans , Iatrogenic Disease , Male , Osteoporosis/drug therapy , Rhinitis, Allergic/drug therapy
9.
BMJ Case Rep ; 20152015 Oct 28.
Article in English | MEDLINE | ID: mdl-26511991

ABSTRACT

The differential diagnosis of febrile pancytopenia in the setting of HIV infection can be challenging. The authors report a case of a 34-year-old man with advanced HIV infection (TCD4=8 cells/mm(3)) and a 2-month history of fever, weight loss and asthaenia. On observation, he was emaciated, hyperthermic and pale, with a haemorrhagic oropharyngeal lesion, penile violaceous lesions and palpable hepatosplenomegaly. Blood tests showed pancytopenia, hyperferritinaemia and hypertriglyceridaemia; imaging confirmed hepatosplenomegaly and a bone marrow biopsy revealed HIV-associated dyshematopoiesis. Biopsy of the aforementioned lesions displayed Kaposi sarcoma; extensive investigation was negative for other opportunistic infections or lymphoproliferative disease. Despite only a posteriori histological documentation, haemophagocytic lymphohistiocytosis (HLH) was considered; chemotherapy and antiretrovirals were started, with excellent response. There was, however, disease relapse requiring an intensification course, with sustained remission at 18-month follow-up. HLH is a rare disease, with non-specific presentation, requiring a high index of suspicion since treatment delay can be fatal.


Subject(s)
HIV Infections/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Adult , Anti-Retroviral Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Diagnosis, Differential , Fever/etiology , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Immunocompromised Host , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Pancytopenia/etiology , Penile Neoplasms/diagnosis , Penile Neoplasms/drug therapy , Sarcoma, Kaposi/diagnosis
10.
PLoS One ; 9(3): e92747, 2014.
Article in English | MEDLINE | ID: mdl-24681625

ABSTRACT

To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.


Subject(s)
Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV Integrase/genetics , HIV-2/drug effects , HIV-2/genetics , Polymorphism, Genetic/genetics , Pyrrolidinones/therapeutic use , Genotype , HIV Integrase Inhibitors/therapeutic use , HIV-1/drug effects , Humans , Raltegravir Potassium
12.
Br J Clin Pharmacol ; 66(4): 551-5, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18662298

ABSTRACT

AIMS: Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included. METHODS: A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period. RESULTS: No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 +/- 1.91 mg l(-1)) vs. co-infected individuals (2.37 +/- 0.37 mg l(-1)). CONCLUSION: It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.


Subject(s)
Benzoxazines/therapeutic use , HIV Infections/drug therapy , Hepatitis B, Chronic/drug therapy , Hepatitis C, Chronic/drug therapy , Reverse Transcriptase Inhibitors/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , Adult , Alkynes , Benzoxazines/pharmacokinetics , CD4 Lymphocyte Count , Case-Control Studies , Cyclopropanes , Disease Progression , Dose-Response Relationship, Drug , Drug Monitoring , Female , Follow-Up Studies , HIV Infections/metabolism , Hepatitis B, Chronic/metabolism , Hepatitis C, Chronic/metabolism , Humans , Liver Diseases/complications , Liver Diseases/drug therapy , Male , Pilot Projects , Reverse Transcriptase Inhibitors/pharmacokinetics , Severity of Illness Index , Treatment Outcome , Viral Load
13.
Ther Drug Monit ; 30(1): 60-6, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18223464

ABSTRACT

Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intra-individual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27%, 31%, and 25%, ranging from 12% to 63%. No differences in intrapatient variability in efavirenz plasma concentrations were found between females and males, HBV/HCV and HBV/HCV patients, or age above/below 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42%), 1.52 (16%), and 1.68 (45%). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40%) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation.


Subject(s)
Anti-HIV Agents/blood , Benzoxazines/blood , Drug Monitoring/methods , Reverse Transcriptase Inhibitors/blood , Adolescent , Adult , Aged , Alkynes , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/therapeutic use , Benzoxazines/pharmacokinetics , Benzoxazines/therapeutic use , Chromatography, High Pressure Liquid , Cyclopropanes , Female , HIV Infections/drug therapy , Humans , Male , Middle Aged , Reverse Transcriptase Inhibitors/pharmacokinetics , Reverse Transcriptase Inhibitors/therapeutic use
14.
Br J Clin Pharmacol ; 61(5): 601-4, 2006 May.
Article in English | MEDLINE | ID: mdl-16669853

ABSTRACT

AIMS: To investigate the long-term effects of efavirenz on cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG). METHODS: Thirty-four HIV-infected patients who commenced efavirenz therapy were monitored for 36 months. RESULTS: In patients with baseline HDL-C<40 mg.dL-1 an increase in HDL-C from 31+/-1 mg.dL-1 to 44+/-2 mg.dL-1 (95% confidence interval 5.9, 21.9, P<0.01) was observed and remained throughout the follow-up period. Median efavirenz plasma concentration was 1.98 mg.L-1 and a direct correlation between percentage of HDL-C variation or TC/HDL-C ratio and efavirenz plasma concentrations was found. CONCLUSIONS: There is evidence of a long-term and concentration-dependent beneficial effect of efavirenz on HDL-C in HIV-infected patients.


Subject(s)
Cholesterol, HDL/blood , HIV Infections/drug therapy , HIV-1 , Oxazines/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Adult , Alkynes , Benzoxazines , Cholesterol/blood , Cyclopropanes , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Glycoproteins/blood , HIV Infections/blood , Humans , Male , Prospective Studies , Time Factors , Treatment Outcome
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