RESUMO
Single-tablet regimens (STRs) of highly safe and effective combination antiretroviral therapy (cART) have had a significant beneficial impact on the clinical outcomes and lives of people living with HIV (PLHIV). As a consequence, healthcare professionals caring for PLHIV in high-income countries have increasingly focused on issues beyond those related to HIV itself, i.e. HIV-related neurological disease, or associated opportunistic infections, which include co-infections, and primarily age- and lifestyle-related comorbidities such as cardiovascular disease, diabetes mellitus, renal impairment, osteoporosis and frailty. This review considers drug side effects and comorbidities seen in PLHIV and evaluates the role of a recently licensed STR - bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) - in mitigating some of those challenges. Factors that need to be evaluated for initial cART regimens include: pretreatment CD4 cell count; plasma HIV RNA; HIV drug resistance; hepatitis B co-infection; HLA-B*5701 status; drug-drug interactions; pregnancy and pregnancy potential; psychiatric and physical comorbidities such as renal or bone disease, as well as simplicity and adherence-friendliness, all of which need to be considered in all lines of therapy. BIC/FTC/TAF constitutes a new STR that includes an unboosted integrase strand transfer inhibitor with a high barrier against resistance with TAF and FTC. Its virological efficacy was non-inferior to dolutegravir-based regimens previously recommended by most guidelines for treatment initiation in large double-blind, randomised clinical trials in treatment-naïve or switch patients over 96 weeks. Tolerability and pharmacological properties of the regimen make it a useful tool to address several of the clinical management issues raised above.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Tenofovir/efeitos adversos , Adenina/efeitos adversos , Adenina/uso terapêutico , Alanina , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Comorbidade , Combinação de Medicamentos , Emtricitabina , Estudos de Equivalência como Asunto , Infecções por HIV/sangue , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Piperazinas , Piridonas , Fatores de Risco , Fatores Socioeconômicos , Comprimidos , Tenofovir/uso terapêuticoRESUMO
OBJECTIVES: The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection. METHODS: We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay). RESULTS: The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group. CONCLUSIONS: There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.
Assuntos
Infecções por HIV/epidemiologia , Hepatite C/genética , Polimorfismo de Nucleotídeo Único , Receptor CB2 de Canabinoide/genética , Adulto , Coinfecção/epidemiologia , Estudos Transversais , Feminino , Predisposição Genética para Doença , Infecções por HIV/genética , Infecções por HIV/metabolismo , Hepatite C/epidemiologia , Hepatite C/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Minorias Sexuais e de Gênero/classificaçãoRESUMO
OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Adulto , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: After the advent of ART, non-AIDS-related comorbidities are the main causes of death in HIV patients. Multiple biomarkers have been studied as markers of disease. We wanted to test soluble endothelial protein C receptor (sEPCR) in an HIV setting. OBJECTIVES: The primary objective was to determine whether sEPCR decreases after 48 weeks of ART in naive HIV patients. Secondary objectives were to compare sEPCR levels between patients with chronic HIV infection (CHI) and primary HIV infection (PHI) and to analyse if there is a correlation between sEPCR and both immunovirological parameters and different markers of inflammation. PATIENTS AND METHODS: We analysed sEPCR in 33 patients with CHI and 19 patients with PHI naive to ART. sEPCR was compared together with immunovirological parameters (HIV RNA and CD4 cell count) and IL-6 or D-dimer (DD). RESULTS AND CONCLUSIONS: After 48 weeks of ART, in CHI, the sEPCR decrease was significant (Pâ=â0.0006) and sEPCR at baseline was correlated with both CD4 cell increase (râ=â+0.463, Pâ=â0.007) and HIV RNA decrease (râ=â-0.363, Pâ=â0.038). In PHI, sEPCR was stable (Pâ=â0.35); there was a correlation between 48 week DD change and IL-6 change (râ=â+0.696, Pâ=â0.0009) and also between 48 week DD change and sEPCR change (râ=â+0.553, Pâ=â0.014). Despite the small sample size, we hypothesize that sEPCR levels reflect coagulant pathway activation caused by the endothelial damage during chronic infection more than a marker of the cytokine storm that occurs during PHI. Alternatively, in PHI, the link found between sEPCR and DD secondary to IL-6 suggests sEPCR is an indirect marker of inflammation.
Assuntos
Antirretrovirais/uso terapêutico , Antígenos CD/sangue , Terapia Antirretroviral de Alta Atividade , Biomarcadores/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Inflamação/patologia , Receptores de Superfície Celular/sangue , Adulto , Contagem de Linfócito CD4 , Receptor de Proteína C Endotelial , Feminino , Humanos , Masculino , Estudos Prospectivos , Carga ViralRESUMO
OBJECTIVES: Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals. METHODS: Mixed models were used to analyse the natural history of HCV RNA changes over time in HIV-positive patients with chronic HCV infection. RESULTS: A total of 1541 individuals, predominantly White (91%), male (73%), from southern (35%) and western central Europe (23%) and with HCV genotype 1 (58%), were included in the analysis. The median follow-up time was 5.0 years [interquartile range (IQR) 2.8 to 8.3 years]. Among patients not on combination antiretroviral therapy (cART), HCV RNA levels increased by a mean 27.6% per year [95% confidence interval (CI) 6.1-53.5%; P = 0.0098]. Among patients receiving cART, HCV RNA levels were stable, increasing by a mean 2.6% per year (95% CI -1.1 to 6.5%; P = 0.17). Baseline HCV RNA levels were 25.5% higher (95% CI 8.8 to 39.1%; P = 0.0044) in individuals with HCV genotype 1 compared with HCV genotypes 2, 3 and 4. A 1 log HIV-1 RNA copies/mL increase in HIV RNA was associated with a 10.9% increase (95% CI 2.3 to 20.2%; P = 0.012) in HCV RNA. CONCLUSIONS: While HCV RNA levels increased significantly in patients prior to receiving cART, among those treated with cART HCV RNA levels remained stable over time.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Carga Viral , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Estudos Prospectivos , RNA Viral/sangueRESUMO
OBJECTIVES: The aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients. METHODS: An adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the χ(2) test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses. RESULTS: Among 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 ± 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019). CONCLUSIONS: In this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Carbamatos/administração & dosagem , Desoxicitidina/análogos & derivados , Didesoxinucleosídeos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lamivudina/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Nevirapina/administração & dosagem , Oligopeptídeos/administração & dosagem , Organofosfatos/administração & dosagem , Organofosfonatos/administração & dosagem , Oxazinas/administração & dosagem , Piridinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adenina/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Sulfato de Atazanavir , Contagem de Linfócito CD4 , Estudos Transversais , Desoxicitidina/administração & dosagem , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Feminino , Furanos , Infecções por HIV/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários , Carga ViralRESUMO
OBJECTIVES: To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors. METHODS: Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of patients in Group HIV/HCV were on an antiretroviral regimen. RESULTS: HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm(3)). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis. CONCLUSION: The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.
Assuntos
Coinfecção/patologia , Coinfecção/virologia , Infecções por HIV/patologia , Hepatite C/patologia , Cirrose Hepática/virologia , Adulto , Distribuição de Qui-Quadrado , Feminino , Genótipo , HIV/isolamento & purificação , Infecções por HIV/virologia , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Necrose/patologia , Necrose/virologia , PrevalênciaRESUMO
OBJECTIVE: As a proactive diagnosis of diabetes mellitus (DM) may prevent the onset of severe complications, we used an oral glucose tolerance test (OGTT) to check for impaired glucose tolerance (IGT) and DM in patients with long-standing HIV infection and long durations of exposure to antiretroviral drugs with normal fasting plasma glucose (FPG) levels. METHODS: This was a cross-sectional, single-centre study. The homeostatic model assessment for insulin resistance (HOMA-IR) and 2-h post-load glucose levels were used to evaluate patients with known HIV-1 infection since before 1988 and no previous diagnosis of DM for whom data on hepatitis C virus (HCV) and hepatitis B virus (HBV) infection were available. RESULTS: Eighty-four Caucasian patients [67 (80%) male; median age 45.7 years; range 43.8-49.1 years] were able to be evaluated; 65 (77%) were coinfected with HCV, and seven (8%) were coinfected with HBV. Median (interquartile range [IQR]) exposure to antiretrovirals was 12.8 (10.4-16.5) years. Fifteen patients (18%) had a previous AIDS-defining event, 64 (76%) had HIV RNA<50 copies/mL, and the median (IQR) CD4 count was 502 (327-628) cells/µL. The median [IQR] FPG was 81 mg/dL (4.5 mmol/L) [75-87 mg/dL (4.2-4.8 mmol/L)], and the median (IQR) HOMA-IR was 2.82 (1.89-4.02). After OGTT, nine patients (11%) were diagnosed as having IGT (6) or DM (3). A first multivariable analysis showed that CD4 cell count (P=0.038) and HOMA-IR (P=0.035) were associated with IGT or DM, but a second model including only the variables with a P-value of <0.2 in the univariable analysis (CD4 cell count, HBV coinfection, and HOMA-IR) found that only HOMA-IR independently predicted IGT or DM. CONCLUSIONS: In patients with long-standing HIV infection and normal FPG levels, an OGTT can reveal IGT or DM.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Intolerância à Glucose/diagnóstico , Teste de Tolerância a Glucose , Infecções por HIV/complicações , HIV-1 , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: We investigated the effects of maraviroc, the first approved CC-chemokine receptor 5 (CCR5) antagonist, on blood lipids in a post hoc analysis of the phase 3 MERIT study in treatment-naïve patients. METHODS: Patients received maraviroc 300 mg twice daily (n = 360) or efavirenz 600 mg once daily (n = 361), both in combination with zidovudine/lamivudine, for up to 96 weeks. Baseline and on- treatment lipid profiles were analyzed according to National Cholesterol Education Program (NCEP) thresholds. RESULTS: Baseline characteristics and lipid profiles were comparable between groups. Among patients with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) below NCEP treatment thresholds at baseline, significantly more efavirenz- than maraviroc-treated patients exceeded those thresholds at 96 weeks (TC: 35% [74/209] vs 11% [20/188], P < .0001; LDL-c: 23% [47/197] vs 8% [15/183], P < .0001). Among patients exceeding NCEP thresholds at baseline, significantly more efavirenz- than maraviroc-treated patients exceeded the thresholds at 96 weeks (TC: 83% [24/29] vs 50% [17/34], P = .0084; LDL-c: 86% [19/22] vs 55% [16/29], P = .0314). Of those with baseline high- density lipoprotein cholesterol (HDL-c) < 40 mg/dL, 43% (56/130) of maravirocand 62% (86/139) of efavirenz-treated patients achieved HDL-c≥40 mg/dL at 96 weeks (P = .0020). CONCLUSIONS: Maraviroc was not associated with elevations in TC, LDL-c, or triglycerides and showed beneficial effects on lipid profiles of dyslipidemic patients.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Cicloexanos/administração & dosagem , Dislipidemias/tratamento farmacológico , Dislipidemias/virologia , Infecções por HIV/sangue , HIV-1/isolamento & purificação , Triazóis/administração & dosagem , Adulto , Alcinos , Antagonistas dos Receptores CCR5 , Distribuição de Qui-Quadrado , Colesterol/sangue , Ciclopropanos , Dislipidemias/sangue , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Maraviroc , Receptores CCR5/metabolismo , Triglicerídeos/sangueRESUMO
BACKGROUND AND OBJECTIVE: The prevalence and clinical significance of overt hepatitis B (OHB) in human immunodeficiency virus (HIV)-infected individuals and the effect of HAART on this cryptic infection remain controversial. We have investigated the potential effect of the interruption and subsequent re-introduction of highly active antiretroviral therapy (HAART) on the frequency and dynamics of OHB in HIV-infected individuals. STUDY DESIGN: This pilot study involved 29 HIV-infected individuals who tested positive for HB anti-core antibodies in the absence of surface antigen during a 100-week period (48-week-long interruption of HAART or lamivudine monotherapy plus 52 weeks of follow-up prior to HAART resumption). The frequency and dynamics of OHB were assessed by means of qualitative detection tests and quantification in the plasma. Resistance to HBV was determined by direct sequence analysis of the polymerase gene. RESULTS: Of the 29 HIV-infected individuals enrolled in the study, nine (31%) showed signs of OHB during the 100-week study period: three patients showed intermittent HB virus (HBV)-DNAemia, while six patients were HBV-DNA positive only at 16 weeks following HAART resumption. The HBV-DNA load invariably fell below the sensitivity of the quantitative test (10(3 )copies/mL). The HIV-related immuno-virologic profile and biochemical parameters, including hepatic transaminases, of patients with at least one HBV-DNA positive test result were not significant different from those of individuals who consistently tested negative for HBV-DNA. The only significant parameter was a lower median change (Δ1) in the CD4+/CD8+ ratio (p = 0.038) in occult HBV cases compared to non-occult cases, between the HAART re-introduction time point and baseline. CONCLUSIONS: The intermittent nature of HBV-DNAemia poses a diagnostic challenge, but no association was found with transaminase levels at any time.
Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , DNA Viral/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Anticorpos Anti-Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Comorbidade , DNA Viral/genética , Farmacorresistência Viral , Feminino , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNARESUMO
OBJECTIVE: To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF) 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU). METHODS: European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naive, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. RESULTS: Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing=failure) at week 48, 34% of patients (23/67; 95% CI: 23%-47%) had plasma HIV-1 RNA <50 copies/mL. Using an intent-to-treat missing=excluded approach, the week 48 proportion of patients with plasma HIV-1 RNA <50 copies/mL increased to 56% (23/41; 95% CI: 40%-72%). Mean (standard deviation) increase from baseline in CD4+ cell count at week 48 was 176 (242) cells/mm(3). Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. CONCLUSIONS: Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adesão à Medicação , Metadona/uso terapêutico , Organofosfonatos/uso terapêutico , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Adenina/uso terapêutico , Adulto , Analgésicos Opioides/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , Seguimentos , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Taxa de Sobrevida , Tenofovir , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
Despite repeated exposure to HIV-1, certain individuals remain persistently uninfected. Such exposed uninfected (EU) people show evidence of HIV-1-specific T cell immunity and, in rare cases, selective resistance to infection by macrophage-tropic strains of HIV-1. The latter has been associated with a 32-base pair deletion in the C-C chemokine receptor gene CCR-5, the major coreceptor of macrophage-tropic strains of HIV-1. We have undertaken an analysis of the HIV-specific T cell responses in 12 EU individuals who were either homozygous for the wild-type CCR-5 allele or heterozygous for the deletion allele (CCR-5Delta32). We have found evidence of an oligoclonal T cell response mediated by helper T cells specific for a conserved region of the HIV-1 envelope. These cells produce very high levels of C-C chemokines when stimulated by the specific antigen and suppress selectively the replication of macrophage-tropic, but not T cell-tropic, strains of HIV-1. These chemokine-producing helper cells may be part of a protective immune response that could be potentially exploited for vaccine development.
Assuntos
Alelos , Fármacos Anti-HIV/imunologia , Linfócitos T CD4-Positivos/virologia , Quimiocinas/fisiologia , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/fisiologia , HIV-1/fisiologia , Receptores de Citocinas/genética , Receptores de HIV/genética , Sequência de Aminoácidos , Linfócitos T CD4-Positivos/imunologia , Quimiocinas/biossíntese , Células Clonais , Genótipo , HIV-1/genética , Humanos , Ativação Linfocitária/genética , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/imunologia , Receptores CCR5 , Replicação Viral/imunologiaRESUMO
OBJECTIVE: To investigate the impact of intermittent interleukin-2 (IL-2) plus combination antiretroviral therapy (cART) on HIV-1 entry co-receptor use. METHODS: Primary HIV-1 isolates were obtained from 54 HIV-1-positive individuals at baseline and after 12 months using co-cultivation of peripheral blood mononuclear cells (PBMC) with activated PBMC of HIV-negative healthy donors. HIV-1 co-receptor use was determined on U87-CD4 cells. RESULTS: Fourteen out of the 21 (67%) IL-2-treated individuals harbouring a primary CCR5-dependent (R5) HIV-1 isolate at baseline confirmed an R5 virus isolation after 12 months in contrast to 3 out of 7 (43%) of those receiving cART only. After 12 months, only 1 R5X4 HIV-1 isolate was obtained from 21 cART+IL-2-treated individuals infected with an R5 virus at entry (5%) vs. 2/7 (29%) patients receiving cART alone, as confirmed by a 5-year follow-up on some individuals. CONCLUSIONS: Intermittent IL-2 administration plus cART may prevent evolution towards CXCR4 usage in individuals infected with R5 HIV-1.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/virologia , HIV-1/fisiologia , Interleucina-2/administração & dosagem , Receptores CCR5/metabolismo , Linfócitos T CD4-Positivos , Células Cultivadas , Ensaios Clínicos Controlados como Assunto , Progressão da Doença , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Humanos , Leucócitos Mononucleares , Viremia/diagnósticoRESUMO
INTRODUCTION: Occult HBV infection is characterized by the absence of surface antigenemia and the presence of potentially infectious hepatitis B virus (HBV)-DNA present in liver, serum, or both. Reactivation of chronic HBV infection in the presence of the HBV surface antigen (HBsAg) is a well-known complication in immunocompromised individuals under cytotoxic chemotherapy or in HIV-infected individuals when nucleos(t)ide analogs effective against HIV/HBV are discontinued. However, little is known on the possibility of such a complication in HIV-infected persons with HBV-core antibody (anti-HBc) as the sole serological marker of past HBV infection. CASE PRESENTATION: Here we report the case of one HIV-infected, anti-HBc-positive individual who showed a severe reactivation of HBV after the interruption of antiretroviral therapy (ART). RESULTS: Analysis of the plasma samples revealed HBV-DNaemia, albeit at very low levels in the latent phase, while the HBV-DNA level was highly increased during the overt phase that corresponded to the period of ART interruption, decreasing dramatically after the subsequent introduction of tenofovir-based ART. Molecular analysis of HBV in the two phases showed that overt HBV infection was due to reactivation of the occult HBV rather than to reinfection. CONCLUSIONS: Our case underlines the possibility that occult HBV infection may still have the potential to be severely reactivated in HIV-infected individuals, particularly when antiretroviral treatment is discontinued.
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Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Ativação Viral , Suspensão de Tratamento , Sequência de Aminoácidos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepatite B/complicações , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Ativação Viral/efeitos dos fármacosRESUMO
The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.
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Corticosteroides/uso terapêutico , Tratamento Farmacológico da COVID-19 , Carga Viral/efeitos dos fármacos , Fatores Etários , Idoso , COVID-19/epidemiologia , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoAssuntos
Fármacos Anti-HIV/farmacocinética , Cicloexanos/farmacocinética , Infecções por HIV/tratamento farmacológico , Lopinavir/farmacocinética , Ritonavir/farmacocinética , Sêmen/química , Triazóis/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Cicloexanos/administração & dosagem , Humanos , Lopinavir/administração & dosagem , Masculino , Maraviroc , Pessoa de Meia-Idade , Plasma/química , Ritonavir/administração & dosagem , Triazóis/administração & dosagemRESUMO
BACKGROUND: This phase IIb study explored the antiviral activity and safety of the investigational CC chemokine receptor 5 (CCR5) antagonist aplaviroc (APL) in antiretroviral-naïve patients harbouring R5- or R5X4-tropic virus. METHODS: A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100 mg bid. Efficacy, safety and pharmacokinetic parameters were assessed. RESULTS: This study was terminated prematurely because of APL-associated idiosyncratic hepatotoxicity. A total of 141 patients initiated treatment early enough to have been able to complete 12 weeks on treatment [modified intent-to-treat (M-ITT) population]; of these, 133 completed the 12-week treatment phase. The proportion of subjects in the M-ITT population with HIV-1 RNA <400 copies/mL at week 12 was 50, 48, 54 and 75% in the APL 200 mg bid, APL 400 mg bid, APL 800 mg once a day (qd) and 3TC/ZDV arms, respectively. Similar responses were seen in the few subjects harbouring R5X4-tropic virus (n=17). Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated nonlinear pharmacokinetics with high interpatient variability. CONCLUSIONS: While target plasma concentrations of APL were achieved, the antiviral activity of APL+LPV/r did not appear to be comparable to that of 3TC/ZDV+LPV/r.
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Benzoatos/toxicidade , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Piperazinas/toxicidade , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Compostos de Espiro/toxicidade , Adulto , Idoso , Benzoatos/farmacocinética , Dicetopiperazinas , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacocinética , HIV-1/imunologia , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacocinética , Pirimidinonas/farmacocinética , RNA Viral/imunologia , Receptores CCR5/uso terapêutico , Ritonavir/farmacocinética , Compostos de Espiro/farmacocinética , Adulto JovemRESUMO
This study examined the impact of L-acetylcarnitine treatment on metabolic parameters and body composition in patients with lipodystrophy syndrome secondary to antiretroviral treatment in human immunodeficiency virus (HIV) infection. A total of 9 HIV-1 infected patients with lipodystrophy syndrome (4F/5M, age 41+/-5 years, HIV duration 8+/-2 years, BMI 23.7+/-3.4 kg/m(2), on protease inhibitors and nucleoside analogue Reverse Transcriptase inhibitors) were evaluated before and after 8 months of therapy with L-acetylcarnitine (2 g/die) and 9 matched healthy subjects served as control subjects. In all patients fasting plasma glucose, insulin concentrations (for evaluation of surrogate indexes of insulin sensitivity), lipid profile, lipid oxidation (by indirect calorimetry), body composition (by DEXA), and intramyocellular triglyceride (IMCL) content of the calf muscles (by (1)H NMR spectroscopy) were assessed. After this therapy, in HIV-1 patients, the IMCL content of the soleus had significantly decreased (p=0.03). Plasma FFAs (0.79+/-0.31 to 0.64+/-0.25; p<0.05) and Respiratory Quotient (0.83+/-0.18 to 0.72+/-0.16; p<0.03) also decreased. Insulin sensitivity was significantly lower prior (HOMA-IS 0.56+/-0.30) and nonstatistically different than controls after therapy (0.72+/-0.49 vs. 0.78+/-0.42) whilst the percentage of fat in the legs increased (p=0.05). Eight months of L-acetylcarnitine treatment increased lipid oxidation, decreased intramyocellular triglyceride content, and induced a more physiological distribution of fat deposits.
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Acetilcarnitina/uso terapêutico , Composição Corporal/efeitos dos fármacos , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Adulto , Glicemia , Estudos de Casos e Controles , Feminino , Síndrome de Lipodistrofia Associada ao HIV/sangue , Humanos , Insulina/sangue , Lipídeos/sangue , Pessoa de Meia-IdadeRESUMO
BACKGROUND: An evaluation of the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals is important as HBV infection may have an impact on the outcome of the liver disease in these patients. MATERIALS AND METHODS: Of the 1,593 HIV-positive subjects enrolled in the Italian Cohort Naïve Antiretroviral (ICONA) program, 175 (10.9%) were selected for inclusion in the study on the basis of hepatitis B surface antigen (HBsAg) negativity and antibody to hepatitis B core antigen (anti- HBc) positivity; 101/175 (58%) were also anti-hepatitis C virus (HCV) positive. HBV-DNA was detected in plasma using a highly sensitive PCR assay (detection limit: 2.6 copies/ml). Two different genomic regions were assayed. Quantification was performed by real-time PCR. The HBV genotype was determined in 20 cases with occult HBV infection. Data on the antiretroviral therapy (ART) regimen was obtained in 169 individuals: 53 (31.4%) patients were ART-naive, 46 (27.2%) were under ART without lamivudine or tenofovir, and the remaining 70 (41.4%) were under ART including lamivudine or tenofovir. RESULTS: 27/175 (15%) patients had detectable HBV-DNA in their plasma: 21/101 (21%) were anti-HCV positive and 6/74 (8%) were anti-HCV negative. Genotype D was invariably found in the 20 cases analyzed. Occult HBV infection was significantly higher in HCV-coinfected subjects: adjusted OR 5.02, 95% CI 1.31-19.26, p = 0.02. The value was not associated with immune status, HIV load, or ART regimen. CONCLUSIONS: In relation to the high prevalence of occult HBV infection, particularly in HIV/HCV-coinfected individuals, it is necessary to clarify the clinical impact of this cryptic infection by monitoring HBV-DNA in plasma using the correct approach. Similarly to HBsAg-positive individuals of the Mediterranean area, HBV genotype D is invariably detected in this cohort of HIV-infected patients with occult HBV infection.