RESUMO
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: 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
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
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
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
Humanos , Adolescente , Síndrome da Imunodeficiência Adquirida/diagnóstico , Revelação/estatística & dados numéricos , Pesquisa QualitativaRESUMO
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
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
BACKGROUND: The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. METHODS: PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end. RESULTS: Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were <400 copies/mL 24 weeks later. CONCLUSIONS: Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance
Assuntos
Humanos , Criança , Resistência a Medicamentos , HIV , Terapia Antirretroviral de Alta Atividade , Virologia , CriançaRESUMO
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
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.