RESUMO
BACKGROUND: Despite an effective vaccine, hepatitis B remains a major global health problem due to its significant morbidity and mortality. Vaccination in immunosuppressed patients such as those treated for an inflammatory bowel disease (IBD) can be less effective. This case describes an uncommon original diagnosis of an acute hepatitis B infection occurring in a vaccinated but immunocompromised IBD patient under long-term infliximab treatment. A low anti-HBs titer and the presence of HBsAg escape mutations are possible hypotheses to explain this unexpected infection. CASE PRESENTATION: A 28-year-old Caucasian male, regularly followed-up for a Crohn's disease treated by infliximab, was regularly screened for sexually transmissible infections because of at-risk behaviors. Despite a correct immunization scheme against hepatitis B virus (HBV), an active HBV infection was diagnosed during one of those screenings. Retrospective testing of a sample collected 6 months earlier was in favor of an evolution from an acute hepatitis B toward a chronic hepatitis B. The patient has always had a low anti-HBs antibody levels (near the threshold of 10 IU/L) possibly explaining his infection. In addition, HBV sequencing revealed a genotype A2 HBV strain, carrying the sD144A substitution on the S protein, known as a potential immune escape variant. Dual therapy combining tenofovir disoproxil fumarate and emtricitabine, active against HBV but also efficient as an HIV pre-exposure prophylaxis, was initiated. Ten months after treatment initiation, all surrogate biochemical and virological endpoints for HBV functional cure were achieved. Treatment and periodical monitoring are being maintained. CONCLUSION: Emphasis should be placed on HBV screening, vaccination and regular monitoring of patients under long-term immunosuppressive therapy, particularly those with at-risk behaviors.
Assuntos
Hepatite B , Doenças Inflamatórias Intestinais , Adulto , Anticorpos Anti-Hepatite B/uso terapêutico , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/genética , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Masculino , Estudos Retrospectivos , VacinaçãoRESUMO
INTRODUCTION: Mitochondrial dysfunction is a classic complication of HIV infection and its treatment and has also been reported in hepatitis C virus (HCV)-infected patients. Little is known about interactions between both viruses on mitochondrial metabolism. METHODS: We performed a cross-sectional study of HCV-infected patients who underwent liver biopsy as part of their routine care. Mitochondrial function was assessed by (a) liver morphological (histology) and functional (spectro-photometry) studies, and (b) serum lactate kinetics, oxygen uptake, and anaerobic threshold measurement during standardized incremental exercise. Three predefined groups of patients were compared. RESULTS: Thirty-eight HCV-infected patients were included: 13 not HIV infected (group 1), 7 with HIV co-infection and low nucleoside reverse transcriptase inhibitor (NRTI) exposure (none over the last 2 years; group 2), and 18 with HIV co-infection and high NRTI exposure (group 3). On liver biopsies, respiratory chain complex IV activity was impaired, at 5 (2-7) nmol/min/mg substrates in group 1, 5 (3-8) in group 2, and 8 (2-13) in group 3 (normal values, 20-56). Maximal power output was diminished and anaerobic threshold occurred earlier in HIV-infected patients, regardless of NRTI exposure. CONCLUSION: HCV has deleterious effects on liver mitochondrial metabolism, notably on respiratory chain complex IV. No significant interaction with HIV was observed.
Assuntos
Infecções por HIV/complicações , HIV/isolamento & purificação , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Mitocôndrias Hepáticas/patologia , Adulto , Biópsia , Estudos Transversais , Feminino , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepatite C/patologia , Hepatite C/virologia , Histocitoquímica , Humanos , Lactatos/sangue , Modelos Lineares , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Mitocôndrias Hepáticas/metabolismo , Consumo de OxigênioRESUMO
INTRODUCTION: Previous studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long-term antiretroviral therapy (ART) in individuals treated since acute and early HIV-1 infection (AHI). METHODS: Data were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long-term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection. RESULTS: The participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre-ART viral loads were lower in women than men, 5.2 and 5.6 log10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4+ T-cell count and CD4:CD8 ratio during the first months of treatment. Sex-related differences in CD4+ T-cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4+ T-cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log10 copies/106 PBMCs after 70 months of ART for both sexes). CONCLUSIONS: The high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , HIV-1/imunologia , Humanos , Leucócitos Mononucleares , Estudos Longitudinais , Masculino , Fatores Sexuais , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Prevalence of HIV-1 non-B subtypes has increased overtime in patients diagnosed at the time of primary infection (PHI) in France. Our objective was to characterize in detail non-B strains which could not be genetically classified into the known subtypes/Circulating Recombinant Forms (CRFs). METHODS: Among 744 patients enrolled in the ANRS PRIMO Cohort since 1996, 176 (23.7%) were infected with HIV-1 non-B strains. The subtype/CRF could not be identified in RT for 15 (2%). The V3-V5 env region was sequenced and 3 strains (04FR-KZS, 06FR-CRN, 04FR-AUK) were full-length sequenced. Phylogenetic and bootscan analyses were used to characterize the mosaic structures. RESULTS: Among V3-V5 sequences, 6 were divergent A, 2 distantly related to E or D, 2 C, 1 B and 2 remained unclassified. 04FR-KZS, isolated in a Congolese woman infected in France, clustered with 2 previously described viruses from the Democratic Republic of Congo. They represent CRF27_cpx involving A/E/G/H/J/K/U subtypes. 06FR-CRN, isolated in a homosexual Caucasian patient, was a B/C/U recombinant involving a Brazilian C strain. 04FR-AUK, isolated in a Congolese patient infected in France, was a A/K/CRF09/U recombinant clustering from gag to vif with HIV-1 MAL. Others PHI were further observed in 2006-2007 with 1 KZS and 5 CRN-like viruses, suggesting their spread in France. CONCLUSION: This study illustrates the increasing HIV-1 diversity in France associating new (06FR-CRN) and old (CRF27_cpx and "MAL-like" 04FR-AUK) strains, which are rare in their region of origin but may have a possible founder effect in France. Our results strengthen the French guidelines recommending viro-epidemiological surveillance of HIV-1 diversity.
Assuntos
Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Recombinação Genética , Adulto , Feminino , França/epidemiologia , Variação Genética , Genoma Viral , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Proteínas do Envelope Viral/genéticaRESUMO
OBJECTIVE: To evaluate the safety profile and efficacy of salvage regimens containing amprenavir (APV) 600 mg twice daily and ritonavir (RTV) 200 mg twice daily. DESIGN: Prospective, single-center study. METHOD: The patient database of the department of infectious diseases was screened for patients who had failed at least two successive three-drug combinations. These patients were proposed to take APV and RTV in association with two to four other drugs. They were followed monthly for 6 months. RESULTS: Seventeen patients were included. They had been previously treated for 70 +/- 23 months. At baseline, viral load (VL) was 4.86 +/- 0.98 log10 copies/mL and CD4 187 +/- 145 10(6)/L. On week 24, using intent-to-treat analysis, VL decreased to 2.95 +/- 1.59 log10 copies/mL and CD4 increased to 365 +/- 210 10(6)/L. Nine patients (53%) had a VL < 2.3 log10 copies/mL. The most common adverse events were grade 1 or 2 diarrhea and an increase of cholesterol and triglyceride levels. Mean APV trough concentration was 1727 +/- 1749 ng/mL on week 24. CONCLUSION: These data show that the combination of low-dose RTV and reduced doses of APV is safe. This combination can be added to nonnucleoside analogs.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Ritonavir/uso terapêutico , Terapia de Salvação , Sulfonamidas/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Carbamatos , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Furanos , Genótipo , Inibidores da Protease de HIV/efeitos adversos , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fenótipo , Estudos Prospectivos , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Carga ViralAssuntos
Síndrome da Imunodeficiência Adquirida/complicações , Confusão/complicações , Transtornos da Memória/complicações , Oftalmoplegia/complicações , Nutrição Parenteral/efeitos adversos , Deficiência de Tiamina/etiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Confusão/etiologia , Feminino , Humanos , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Tiamina/uso terapêutico , Deficiência de Tiamina/complicaçõesRESUMO
Interferon-α administration during structured treatment interruptions (STIs) was studied in a phase III trial. We randomized 168 chronically infected HIV undetectable under combined antiretroviral therapy patients to have three STIs with or without α-interferon. The number of patients who had to resume treatment during post-STI follow-up was not significantly different between the two arms. Patients with a low CD4 nadir and a high baseline HIV-DNA had a higher risk of treatment resumption in the interferon arm.
Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Interferon-alfa/administração & dosagem , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Doença Crônica , Esquema de Medicação , Humanos , Carga ViralRESUMO
BACKGROUND: In the current context of increasing unsafe sex, HIV incidence may have evolved, depending on HIV prevalence in sexual networks and, among HIV-infected persons who practice unsafe sex, on their infectivity and partners' HIV serostatus. We examined calendar trends in sexual behaviours at risk of HIV-1 transmission (SBR) among 967 adults followed since primary HIV infection (ANRS PRIMO cohort) and relationship with current treatments and viral load. METHODS: Patients completed since 2000 self-administered questionnaires on sexual practices every 6 months. SBR with HIV-negative/unknown partners were analyzed among 155 heterosexual women, 142 heterosexual men and 670 MSM by using logistic generalized estimating equation models (6656 visits). RESULTS: During 2000-2009, the frequency of SBR did not increase significantly among women with steady partners; risk factors were a low education level and alcohol/smoking use. Among heterosexual men with steady partners, the frequency of SBR doubled since 2006; during this period, the only associated factor was combined antiretroviral treatment for at least 6 months or viral load less than 400 copies/ml. Among MSM, SBR increased gradually over time; SBR with steady partners was associated with a low education level and alcohol use. SBR was more frequent among MSM with casual partners; no association with viral load was found. CONCLUSION: In France, recent trends and risk factors in unprotected sex with HIV-negative/unknown partners differ according to sex/sexual preference. The recent increase in SBR among heterosexual men with low viral load may be related to increasing awareness of the 'treatment-as-prevention' concept. The lack of association between SBR and viral load among MSM supports use of treatment-as-prevention as part of diversified prevention strategies.
Assuntos
Infecções por HIV/psicologia , HIV-1 , Heterossexualidade/psicologia , Homossexualidade Masculina/psicologia , Sexo sem Proteção/psicologia , Carga Viral , Adulto , Feminino , França/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Heterossexualidade/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Incidência , Masculino , Fatores de Risco , Inquéritos e Questionários , Sexo sem Proteção/estatística & dados numéricosAssuntos
Infecções por HIV/imunologia , HIV-1 , Vacina contra Febre Amarela/administração & dosagem , Febre Amarela/prevenção & controle , Adulto , Anticorpos Antivirais/sangue , Contagem de Linfócito CD4 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga ViralRESUMO
From 1991 to 2003, 20 patients with pasteurellosis were admitted to our unit, of whom 2 died. They presented with cellulitis (n = 14), arthritis (n = 6), pneumonia (n = 3), subcutaneous abscess (n = 3), bursitis (n = 2), meningitis, otitis, sinusitis and uveitis. Underlying diseases included diabetes (n = 6) and malignancy (n = 5). Diabetes could be a predisposing condition for pasteurellosis.
Assuntos
Diabetes Mellitus , Infecções por Pasteurella/epidemiologia , Infecções por Pasteurella/fisiopatologia , Pasteurella/classificação , Pasteurella/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Causalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pasteurella/microbiologia , Pasteurella multocida/isolamento & purificação , Estudos RetrospectivosRESUMO
BACKGROUND: Lipodystrophy is now widely described in HIV infected patients under antiretroviral regimen with important psychological impact. But physiopathology of loss of fat mass is still debated and the role of mitochondrial impairment is not clearly defined. OBJECTIVE: To correlate clinical lipoatrophy (LA) in HIV patients with long-term treatment by nucleoside reverse transcriptase inhibitors (NRTIs) and muscular impairment related to mitochondrial dysfunction. METHODS: Ten consecutive patients with clinical LA and 10 nonlipodystrophic (NLD) individuals on antiretroviral therapy were included. Patients underwent the following investigations: dual-energy x-ray absorptiometry (DEXA) scanning and lactate kinetics during standardized exercise. The mitochondrial respiratory complex activity (III and IV) and histoenzymatic abnormalities (classified as none, mild, or severe) were evaluated on muscle tissue obtained by biopsy in deltoid muscle. RESULTS: Mean NRTI exposure was longer in the LA group than in the NLD group (81 +/- 30 months vs. 59 +/- 15 months), but mean protease inhibitor exposure was identical in both groups. Mean fat mass distribution for leg in the LA and NLD groups was 860 +/- 381 g versus 1895 +/- 999 g, respectively. The lactic acidosis threshold during exercise was reached in the LA group at lower workloads (mean: 45 +/- 17 W in the LA group vs. 68 +/- 11 W in the NLD group), and maximum power output exercise was restricted in LA patients (mean: 115 +/- 30 W vs. 153 +/- 28 W). Total complex activities in muscular tissue were lower in LA patients: the median (range) for complex III was 67 (1-128) versus 112 (28-143), and the median (range) for complex IV was 28 (1-70) versus 42 (1-75). Six patients had severe histoenzymatic abnormalities in the LA group versus none in the NLD group. CONCLUSION: Clinical LA, confirmed by DEXA, in long-term NRTI-treated patients was associated with muscular mitochondrial dysfunction as shown by rapid lactic acidemia increase, impairment of respiratory chain activity for complexes III and IV, and mitochondrial histoenzymatic abnormalities.