Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study.

Background: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study.

Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.

Background: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents.

Methods: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m) with HIV-1 on daily oral ART were enrolled at 15 centres in four countries (Botswana, South Africa, Thailand, and the USA).

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy.

Objectives: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809).

Design: A Phase 2b, multicenter, open-label, rollover study.

Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study.

Background: In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years.

Methods: After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period.

Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30-49 vs ≥50 mL/min.

A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine dosing in patients with impaired creatinine clearance (CLcr). Safety data collected through 96 weeks were analyzed after stratification by baseline CLcr (estimated using Cockcroft-Gault) of 30-49 mL/min (n = 168) versus ≥50 mL/min (n = 3,132) and treatment regimen. The Grade 3-4 adverse events (AEs) and serious AEs (for hematological, hepatic and gastrointestinal events), maximal toxicities for liver enzymes, serum creatinine and bilirubin and maximum treatment-emergent hematology toxicities were comparable for groups with baseline CLcr 30-49 versus CLcr≥50 mL/min.

Abacavir Use and Risk for Myocardial Infarction and Cardiovascular Events: Pooled Analysis of Data From Clinical Trials.

Background: Some observational studies and randomized controlled trials (RCTs) have suggested an association between abacavir (ABC) use and myocardial infarction (MI), whereas others have not.

Methods: This pooled analysis of 66 phase II-IV RCTs estimates exposure-adjusted incidence rates (IRs) and relative rates (RRs) of MI and cardiovascular events (CVEs) in participants receiving ABC- and non-ABC-containing combination antiretroviral therapy (cART). The primary analysis of MI included ABC-randomized trials with ≥48-week follow-up.

Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection.

Innovation in medicine is a dynamic, complex, and continuous process that cannot be isolated to a single moment in time. Anniversaries offer opportunities to commemorate crucial discoveries of modern medicine, such as penicillin (1928), polio vaccination (inactivated, 1955; oral, 1961), the surface antigen of the hepatitis B virus (1967), monoclonal antibodies (1975), and the first HIV antiretroviral drugs (zidovudine, 1987). The advent of antiretroviral drugs has had a profound effect on the progress of the epidemiology of HIV infection, transforming a terminal, irreversible disease that caused a global health crisis into a treatable but chronic disease.

A prospective study to assess the burden of influenza-related hospitalizations and emergency department visits among children in Bilbao, Spain (2010-2011).

Introduction: This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age.

Patients And Methods: Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture.

Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study.

In children aged ≤4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open-label, four-way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution (ClinicalTrials.gov identifier, NCT02634073).

[A prospective study to assess the burden of influenza-related hospitalizations and emergency department visits among children in Bilbao, Spain (2010-2011)].

Introduction: This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age.

Patients And Methods: Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture.

[Bacterial etiology of acute otitis media in Spain in the post-pneumococcal conjugate vaccine era].

Introduction: Acute otitis media (AOM) is common in children aged <3 years. A pneumococcal conjugate vaccine (PCV) (PCV7; Prevenar, Pfizer/Wyeth, USA) has been available in Spain since 2001, which has a coverage rate of 50-60% in children aged <5 years.

Materials And Methods: Children aged ≥3 to 36 months with AOM confirmed by an ear-nose-throat specialist were enrolled at seven centers in Spain (February 2009-May 2012) (GSK study identifier: 111425).

Seroprevalence of pertussis amongst healthcare professionals in Spain.

Introduction: This multi-center, hospital-based observational study determined the seroprevalence of pertussis antibodies amongst healthcare professionals from three different hospitals in Spain to ascertain the health status of professionals attending to susceptible groups who are at risk of contracting and transmitting pertussis.

Methods: Medical professionals from three hospitals in Spain were recruited for this study (NCT01706224). Serum samples from subjects were assessed for anti-pertussis antibodies by ELISA.

Zidovudine, lamivudine, and abacavir have different effects on resting cells infected with human immunodeficiency virus in vitro.

We have previously described an in vitro model for the evaluation of the effects of different immunomodulatory agents and immunotoxins (ITs) on cells latently infected with human immunodeficiency virus (HIV). We demonstrated that latently infected, replication-competent cells can be generated in vitro after eliminating CD25+ cells with an IT. Thus, by selectively killing the productively infected cells with an anti-CD25 IT we can generate a population of latently infected cells.

Cerebrospinal fluid and plasma concentrations of proinflammatory mediators in human immunodeficiency virus-infected children.

Background: The pathogenesis of HIV encephalopathy is poorly understood especially in children. Studies suggest that HIV replication and the release of proinflammatory mediators in the central nervous system contribute to the pathogenesis of HIV dementia in adults.

Methods: Cerebrospinal fluid (CSF) and plasma samples from 23 HIV-infected children were longitudinally analyzed at Weeks 0, 8, 16 and 48 for HIV RNA and concentrations of the following proinflammatory mediators: monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha, regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-inflammatory protein (MIP)-1-alpha, MIP-1-beta and matrix metalloproteinase-9 (MMP-9).

Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy.

Objectives: This study evaluated the effect of treatment with abacavir/lamivudine/zidovudine versus lamivudine/zidovudine on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA and clinical manifestations of HIV encephalopathy in children.

Study Design: HIV-infected children 7 months to 10 years of age (n = 23) were studied. CSF and plasma were obtained at baseline and weeks 8, 16, and 48.

An anti-CD45RO immunotoxin kills latently infected human immunodeficiency virus (HIV) CD4 T cells in the blood of HIV-positive persons.

Highly active antiretroviral therapy has decreased the morbidity and mortality of human immunodeficiency virus (HIV) infection, but latently infected cells remain for prolonged periods. CD4(+) CD45RO(+) T cells are a major latent virus reservoir in HIV-infected persons. Replication-competent, latently HIV-infected T cells can be generated in vitro by infecting peripheral blood mononuclear cells with HIV and then eliminating the HIV-producing cells with an anti-CD25 immunotoxin (IT).

Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin.

Background: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci.

Purpose And Design: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy.

Results: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen.