RESUMO
This study explored the experiences of the first generation of adolescents who acquired HIV through vertical transmission when disclosing their diagnosis to friends and romantic partners. The study sample was selected by convenience, with 20 patients (13-20 years old) participating in a qualitative investigation using individual interviews (language: Portuguese; duration: 45â minutes). The participants were followed in specialized clinics for the treatment of pediatric AIDS in São Paulo, Brazil. The results suggest that families who live with HIV tend to keep it a secret, and such behavior is learned and accepted unquestioningly as natural. Respect for privacy and the fear of rejection, coupled with the belief that information about their disease will be spread, are the main beliefs with which participants justify their secrecy. In terms of romantic relationships, adolescents were aware that their HIV status should at some point be shared with current or future sexual partners. However, the decision to reveal an HIV diagnosis in romantic relationships is permeated by anxieties, uncertainties about the right time, and fear of abandonment. In any case, telling the truth requires trust, guarantees of the other's love, and, in some cases, probing romantic partners beforehand to learn their perceptions about the disease. Participants who had experiences disclosing their HIV status shared positive and negative results, including emotional support, acceptance, and understanding, along with ostracism, discrimination, and abandonment by family members. The findings of this paper reinforce the challenges of revealing an HIV diagnosis to third parties. It requires understanding the meaning and importance of the secret for each patient, along with the conflict between the right to confidentiality and the responsibility of treating others exposed to the disease. All these aspects should be discussed extensively with this population and incorporated into clinical practice.
Assuntos
Comportamento do Adolescente , Infecções por HIV/psicologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Autorrevelação , Parceiros Sexuais/psicologia , Adolescente , Brasil , Feminino , Infecções por HIV/economia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Adulto JovemRESUMO
Leukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells.
Assuntos
Antígenos CD18/genética , Candidíase/complicações , Herpes Genital/complicações , Leucemia Mieloide Aguda/complicações , Síndrome da Aderência Leucocítica Deficitária/complicações , Antígeno CD11a/genética , Antígeno CD11b/genética , Candidíase/genética , Candidíase/microbiologia , Candidíase/virologia , Progressão da Doença , Evolução Fatal , Feminino , Expressão Gênica , Herpes Genital/genética , Herpes Genital/microbiologia , Herpes Genital/virologia , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/virologia , Síndrome da Aderência Leucocítica Deficitária/genética , Síndrome da Aderência Leucocítica Deficitária/microbiologia , Síndrome da Aderência Leucocítica Deficitária/virologia , Pele , Adulto JovemRESUMO
Our aim was to analyze factors associated with non-adherence to antiretroviral (ARV) treatment among children and adolescents. A cross-sectional study was carried out involving non-institutionalized children and adolescents between 2 and 20 years of age, addressing non-adherence to ARV treatment, which was defined as taking ≤89% of the medications on the day of the interview and the three previous days. The investigation into the association between non-compliance and the variables of interest was performed using unconditional logistic regression. The independent factors associated with non-adherence were forgetfulness (OR = 3.22; 95%CI = 1.75-5.92), difficulties coping with treatment (OR = 2.65; 95%CI = 1.03-6.79), and living with grandparents (OR = 2.28; 95%CI = 1.08-4.83), whereas a protective effect was found with participation in multidisciplinary activities (OR = 0.49; 95%CI = 0.25-0.96), i.e., this factor indicates that the exposure to the variable is beneficial, promoting adherence. We concluded that forgetting to take the medications and reporting having difficulty coping with ARV treatment are potentially modifiable factors through educational and programmatic actions. Residing with one's grandparents may strongly impact adherence to ARV treatment, indicating the need for the systematic support of these family members. Participation in multidisciplinary activities should be stimulated at health-care services.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Equipe de Assistência ao Paciente , Cooperação do Paciente , Adolescente , Terapia Antirretroviral de Alta Atividade , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Autorrelato , Fatores Socioeconômicos , Adulto JovemRESUMO
In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Hipercolesterolemia/induzido quimicamente , Hipertrigliceridemia/induzido quimicamente , Inibidores da Transcriptase Reversa/efeitos adversos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/complicações , Humanos , Hipercolesterolemia/epidemiologia , Hipertrigliceridemia/epidemiologia , América Latina , Modelos Logísticos , Masculino , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. METHODS: The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. RESULTS: The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. CONCLUSIONS: Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Índice de Gravidade de Doença , Carga Viral , Adolescente , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Lactente , Recém-Nascido , América Latina , Masculino , Falha de TratamentoRESUMO
PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.
Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , HIV-1 , Adolescente , Adulto , Fatores Etários , Anti-Infecciosos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Viral , Europa (Continente) , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Sobreviventes de Longo Prazo ao HIV , Hepatite Viral Humana/complicações , Hepatite Viral Humana/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Educação de Pacientes como Assunto , Pneumonia por Pneumocystis/prevenção & controle , Gravidez , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto JovemRESUMO
Antiretroviral therapy contributes to decreasing morbidity and mortality, and ultimately to increasing survival. In Brazil, there are regional differences in HIV epidemiology regarding pregnant women and children with HIV/AIDS. This study evaluates survival time after AIDS diagnosis in 914 children infected by mother-to-child transmission, reported between 1983 and 1998 and followed until 2002, in Brazil's five regions. Time between birth and HIV diagnosis decreased over the years, mainly in the South and Southeast Regions. There was a significant improvement in survival; more than 75% of cases were still living four years after diagnosis in the 1997-1998 group. This Brazilian study demonstrates that even with regional inequalities in health care infrastructure it is possible for a developing country to establish an effective system of universal and free access to antiretroviral therapy that produces a significant increase in survival for children with AIDS.
Assuntos
Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/mortalidade , Síndrome da Imunodeficiência Adquirida/mortalidade , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Infecções por HIV/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Gravidez , Justiça Social , Fatores Socioeconômicos , Análise de SobrevidaRESUMO
The incidence of laryngeal histoplasmosis is low when compared to the total number of cases. Less than 100 cases of laryngeal histoplasmosis have been described in the medical literature. Isolated laryngeal involvement may lead to the misdiagnosis and mistreatment of tuberculosis or laryngeal cancer, according to some reports. The development of hoarseness in a patient with histoplasmosis or a laryngeal mass leading to hoarseness, might be suggestive of laryngeal histoplasmosis. When histoplasmosis is included among the differential diagnoses of a laryngeal lesion, the biopsy should be limited to a small tissue fragment, enough to perform histological tests. The laboratory technicians must be warned about the possibility of histoplasmosis, because special dyes have to be used to confirm this diagnosis.
Assuntos
Histoplasmose/diagnóstico , Doenças da Laringe/diagnóstico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Diagnóstico Diferencial , Fluconazol/uso terapêutico , Histoplasmose/tratamento farmacológico , Humanos , Doenças da Laringe/tratamento farmacológico , Doenças da Laringe/microbiologia , Laringoscopia , MasculinoRESUMO
OBJECTIVE: To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure. METHODS: Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks. RESULTS: One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9). CONCLUSION: In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.
Assuntos
Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adolescente , Brasil , Criança , Pré-Escolar , Farmacorresistência Viral , Europa (Continente) , Feminino , Infecções por HIV/virologia , HIV-1/genética , Humanos , Lactente , Masculino , Especificidade da Espécie , Resultado do TratamentoRESUMO
Community-acquired pneumonia (CAP) is a common cause of hospitalization among people living with human immunodeficiency virus (PLWH), particularly those with severe immunosuppression. Pulmonary disease due to cryptococcosis is uncommonly reported and likely under-diagnosed. There is scarce information about cryptococcal antigen (CrAg) prevalence in PLWH with CAP. The objectives of this study were to identify among PLWH who were hospitalized with CAP: (i) the prevalence of serum CrAg positivity, (ii) the proportion with asymptomatic vs. symptomatic cryptococcosis; and (iii) the prevalence of serum CrAg positivity in CD4þ T-cell count <100 cells/mm3.We performed a sub-analysis of a prospective cohort of hospitalized adults enrolled into a randomized clinical trial testing therapy for CAP. We included 202 participants who had serum CrAg testing performed. We found a 3.5% prevalence of serum CrAg-positivity overall, being higher (5.7%) in CD4þ T-cell count <100 cells/mm3. Overall, asymptomatic and symptomatic cryptococcosis were present in 2.0% and 1.5%, respectively. This study identifies a target population for CrAg testing: PLWH hospitalized with diagnosis of CAP, particularly those with CD4þ T-cell count <100 cells/mm3 where the number needed to test was 18 to detect 1 CrAg-positive person. This approach may facilitate the detection of asymptomatic cryptococcal infection and allow a timely diagnosis of symptomatic cryptococcal disease
Assuntos
Humanos , Pneumonia , Infecções por HIV , CriptococoseRESUMO
BACKGROUND: Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). METHODS: HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. RESULTS: Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. CONCLUSIONS: Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adolescente , Densidade Óssea , Criança , Método Duplo-Cego , Farmacorresistência Viral , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Placebos/administração & dosagem , RNA Viral/sangue , Tenofovir , Falha de Tratamento , Carga ViralRESUMO
UNLABELLED: Brazil was the first developing country to provide free, universal access to antiretroviral treatment for AIDS patients. The Brazilian experience thus provides the first evidence regarding the impact of such treatment on the survival of perinatally acquired AIDS cases in the developing world. MATERIAL AND METHODS: This retrospective cohort study used medical record reviews to examine characteristics and trends in the survival of a representative sample of 914 perinatally acquired AIDS cases in 10 Brazilian cities diagnosed between 1983 and 1998. RESULTS: Survival time increased steadily and substantially. Whereas half of the children died within 20 months of diagnosis at the beginning of the epidemic, 75% of children diagnosed in 1997 and 1998 were still alive after four years of follow-up. CONCLUSIONS: Advances in management and treatment have made a great difference in the survival of Brazilian children with AIDS. These results argue strongly for making such treatment available to children in the entire developing world.
Assuntos
Síndrome da Imunodeficiência Adquirida/mortalidade , Transmissão Vertical de Doenças Infecciosas , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/transmissão , Adolescente , Fármacos Anti-HIV/uso terapêutico , Brasil/epidemiologia , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: To evaluate the long-term (up to week 292) safety, efficacy and tolerability of ritonavir-boosted tipranavir in HIV-1-infected pediatric patients. Long-term follow up of patients enrolled in the randomized, open-label pediatric trial (1182.14/PACTG1051). METHODS: HIV-1-infected pediatric patients (2-18 years) who participated in the PACTG 1051 trial were followed for ritonavir-boosted tipranavir-based regimen efficacy, safety and tolerability through week 292. RESULTS: In patients <12 years of age, 51/62 (82%) were receiving drug at week 48 and 13/62 (21%) at week 288. Among adolescents (12-18 years of age), 35/53 (66%) were receiving drug at week 48 and 2/53 (4%) at week 288. Among patients 2 to <6 years of age, 18/25 (72%) had viral loads <400 copies/mL at week 48. By week 292, 9/25 (36%) of patients had viral loads <400 copies/mL. Among older patients, week 48 responder rates were 35% (13/37 of patients 6 to <12 years of age) and 32% (17/53 of patients 12 to 18 years of age). By week 292, 6/37 (16%) of those 6 to <12 years of age and 2/53 (4%) of those 12 to 18 years of age had viral loads <400 copies/mL. Overall safety and tolerability profiles were best for children who initiated treatment between 2 and <6 years of age. Drug-related adverse events (investigator defined) were similar across all age groups (55-65%). CONCLUSIONS: Pediatric patients who begin treatment at the earlier ages, and who are stable on a ritonavir-boosted tipranavir-based regimen at week 48, generally continue to demonstrate good safety, tolerability and virologic efficacy profiles up to 292 weeks of treatment.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Piridinas/administração & dosagem , Pironas/administração & dosagem , Ritonavir/administração & dosagem , Adolescente , Fármacos Anti-HIV/efeitos adversos , Criança , Pré-Escolar , Combinação de Medicamentos , Infecções por HIV/virologia , Humanos , Piridinas/efeitos adversos , Pironas/efeitos adversos , Ritonavir/efeitos adversos , Sulfonamidas , Carga ViralRESUMO
OBJECTIVES: To evaluate if treatment with ceftriaxone and a macrolide, improved patient outcome when compared with monotherapy with ceftriaxone, in hospitalized patients with human immunodeficiency virus/acquired immunodeficient syndrome (HIV/AIDS) with community-acquired pneumonia (CAP). METHODS: Adult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion (Brazilian Clinical Trials Registry: RBR-8wtq2b). The primary outcome was in-hospital mortality and the secondary outcomes were mortality within 14 days, need for vasoactive drugs, need for mechanical ventilation, time to clinical stability and length of hospitalization. RESULTS: A total of 227 patients were randomized, two were excluded after randomization; 225 patients were analysed (112 receiving ceftriaxone plus placebo and 113 receiving ceftriaxone plus macrolide). The frequency of the primary outcome, in-hospital mortality, was not statistically different between the regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (hazard ratio 1.22, 95% CI 0.57-2.59). We did not find differences between the regimens for any of the secondary outcomes, including mortality within 14 days, which occurred in 5/112 (4%) patients with ceftriaxone plus placebo and in 12/113 (11%) patients with ceftriaxone plus macrolide (relative risk 2.38, 95% CI 0.87-6.53) CONCLUSIONS: Among hospitalized patients with HIV/AIDS with CAP, treatment with ceftriaxone and a macrolide did not improve patient outcomes, when compared with ceftriaxone monotherapy
Assuntos
Humanos , Pneumonia/tratamento farmacológico , Ceftriaxona/uso terapêutico , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , MacrolídeosRESUMO
BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults
Assuntos
Humanos , Criança , HIV-1/efeitos dos fármacos , Maraviroc/farmacocinéticaRESUMO
The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained
Assuntos
Humanos , Criança , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta AtividadeRESUMO
The study of the etiological agents of community-acquired pulmonary infections is important to guide empirical therapy, requires constant updating, and has a substantial impact on the prognosis of patients. The objective of this study is to determine prospectively the etiology of community-acquired pulmonary infections in hospitalized adults living with HIV. Patients were submitted to an extended microbiological investigation that included molecular methods. The microbiological findings were evaluated according to severity of the disease and pneumococcal vaccine status. Two hundred twenty-four patients underwent the extended microbiological investigation of whom 143 (64%) had an etiology determined. Among the 143 patients with a determined etiology, Pneumocystis jirovecii was the main agent, detected in 52 (36%) cases and followed by Mycobacterium tuberculosis accounting for 28 (20%) cases. Streptococcus pneumoniae and Rhinovirus were diagnosed in 22 (15%) cases each and influenza in 15 (10%) cases. Among atypical bacteria, Mycoplasma pneumoniae was responsible for 12 (8%) and Chlamydophila pneumoniae for 7 (5%) cases. Mixed infections occurred in 48 cases (34%). S pneumoniae was associated with higher severity scores and not associated with vaccine status. By using extended diagnostics, a microbiological agent could be determined in the majority of patients living with HIV affected by community-acquired pulmonary infections. Our findings can guide clinicians in the choice of empirical therapy for hospitalized pulmonary disease
Assuntos
Humanos , HIV , Infecções Comunitárias Adquiridas/etiologia , Pneumopatias/microbiologiaRESUMO
BACKGROUND: This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). METHODS: Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. RESULTS: Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. CONCLUSIONS: In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Carga Viral , Criança , Pré-Escolar , Infecções por HIV/virologia , Humanos , Lactente , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents. METHODS: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.8 mg/m(2)) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at week 24 RESULTS: Eighty-seven subjects (45 TDF, 42 placebo) received the study drug. Through week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log(10)copies/mL, P = 0.55). The percentages of subjects who achieved HIV-1 RNA <400 copies/mL were similar at week 24 (40.9 versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4 versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9 versus 33.3%). TDF was generally safe and well tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the 2 groups. CONCLUSION: This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Organofosfonatos , Inibidores da Transcriptase Reversa , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Adolescente , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Criança , Método Duplo-Cego , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Masculino , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , RNA Viral/sangue , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir , Resultado do Tratamento , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
This study explored the experiences of the first generation of adolescents who acquired HIV through vertical transmission when disclosing their diagnosis to friends and romantic partners. The study sample was selected by convenience, with 20 patients (13-20 years old) participating in a qualitative investigation using individual interviews (language: Portuguese; duration: 45â minutes). The participants were followed in specialized clinics for the treatment of pediatric AIDS in São Paulo, Brazil. The results suggest that families who live with HIV tend to keep it a secret, and such behavior is learned and accepted unquestioningly as natural. Respect for privacy and the fear of rejection, coupled with the belief that information about their disease will be spread, are the main beliefs with which participants justify their secrecy. In terms of romantic relationships, adolescents were aware that their HIV status should at some point be shared with current or future sexual partners. However, the decision to reveal an HIV diagnosis in romantic relationships is permeated by anxieties, uncertainties about the right time, and fear of abandonment. In any case, telling the truth requires trust, guarantees of the other's love, and, in some cases, probing romantic partners beforehand to learn their perceptions about the disease. Participants who had experiences disclosing their HIV status shared positive and negative results, including emotional support, acceptance, and understanding, along with ostracism, discrimination, and abandonment by family members. The findings of this paper reinforce the challenges of revealing an HIV diagnosis to third parties. It requires understanding the meaning and importance of the secret for each patient, along with the conflict between the right to confidentiality and the responsibility of treating others exposed to the disease. All these aspects should be discussed extensively with this population and incorporated into clinical practice