Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports ...preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called "superspreading events." Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.
The authors discuss the public health challenges faced by commercial establishments in preventing transmission of Covid-19 among their workers and customers. Also discussed are the benefits and ...limitations of strategies to reduce transmission, ranging from simple measures such as social distancing to more expensive and complex measures such as testing and contact tracing.
The recent announcement of a corporate divorce between two major Boston medical institutions came as a shock to clinicians and the patients whose care it will inevitably disrupt.
Abstract
Background
Initiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight ...may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation.
Methods
We performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naive people living with human immunodeficiency virus (HIV) initiating ART between 2003 and 2015, comprising >5000 participants and 10 000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation.
Results
Weight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Integrase strand transfer inhibitor use was associated with more weight gain than were protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine.
Conclusions
Weight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.
In this report, we use pooled data from randomized clinical trials to identify demographic-, human immunodeficiency virus-, and antiretroviral therapy (ART)–related risk factors for weight gain after the initiation of ART, highlighting the multifactorial nature of ART-associated weight gain.
Rosa Sax, Paul E.
JAMA : the journal of the American Medical Association,
08/2022, Letnik:
328, Številka:
7
Journal Article
Recenzirano
In this narrative medicine essay, an infectious diseases physician tells of the painful decision he and his wife made after hearing the news that a twin fetus had severe cardiac abnormalities.
Integrase strand transfer inhibitors (INSTIs) coadministered with two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are recommended as first-line treatment for HIV, and ...coformulated fixed-dose combinations are preferred to facilitate adherence. We report 48-week results from a study comparing initial HIV-1 treatment with bictegravir—a novel INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug interactions—coformulated with the NRTI combination emtricitabine and tenofovir alafenamide as a fixed-dose combination to dolutegravir administered with coformulated emtricitabine and tenofovir alafenamide.
In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were screened and enrolled at 126 outpatient centres in 10 countries in Australia, Europe, Latin America, and North America. Participants were previously untreated adults (HIV-1 RNA ≥500 copies per mL) with estimated glomerular filtration rate of at least 30 mL/min. Chronic hepatitis B virus or hepatitis C co-infection was allowed. We randomly assigned participants (1:1) to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo, once a day for 144 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received at least one dose of study drug were included in primary efficacy and safety analyses. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of −12%. This study is registered with ClinicalTrials.gov, number NCT02607956.
Between Nov 11, 2015, and July 15, 2016, 742 participants were screened for eligibility, of whom 657 were randomly assigned to treatment (327 with bictegravir, emtricitabine, and tenofovir alafenamide fixed-dose combination bictegravir group and 330 with dolutegravir plus emtricitabine and tenofovir alafenamide dolutegravir group). 320 participants who received the bictegravir regimen and 325 participants who received the dolutegravir regimen were included in the primary efficacy analyses. At week 48, HIV-1 RNA <50 copies per mL was achieved in 286 (89%) of 320 participants in the bictegravir group and 302 (93%) of 325 in the dolutegravir group (difference −3·5%, 95·002% CI −7·9 to 1·0, p=0·12), showing non-inferiority of the bictegravir regimen to the dolutegravir regimen. No treatment-emergent resistance to any study drug was observed. Incidence and severity of adverse events were similar between groups, and few participants discontinued treatment due to adverse events (5 2% of 320 in the bictegravir group and 1 <1% 325 in the dolutegravir group). Study drug-related adverse events were less common in the bictegravir group than in the dolutegravir group (57 18% of 320 vs 83 26% of 325, p=0·022).
At 48 weeks, virological suppression with the bictegravir regimen was achieved and was non-inferior to the dolutegravir regimen in previously untreated adults. There was no emergent resistance to either regimen. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen.
Gilead Sciences Inc.
Background. Contemporary antiretroviral treatment regimens are simpler than in the past, with lower pill burden and once-daily dosing frequency common. We performed a meta-analysis of randomized ...controlled trials (RCTs) to investigate the impact of pill burden and once-daily vs twice-daily dosing on ART adherence and virological outcomes. Methods. A literature search of 4 electronic databases through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART regimens that also reported on adherence and virological suppression were included. Study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Study quality was rated using the Cochrane risk-of-bias tool. Results. Nineteen studies met our inclusion criteria (N = 6312 adult patients). Higher pill burden was associated with both lower adherence rates (P = .004) and worse virological suppression (P < .0001) in both once-daily and twice-daily subgroups, although the association with adherence in the once-daily subgroup was not statistically significant. The average adherence was modestly higher in once-daily regimens than twice-daily regimens (weighted mean difference = 2.55%; 95% confidence interval CI, 1.23 to 3.87; P = .0002). Patients on once-daily regimens did not achieve virological suppression more frequently than patients on twice-daily regimens (relative risk RR = 1.01; 95% CI, 0.99 to 1.03; P = .50). Both adherence and viral load suppression decreased over time, but adherence decreased less with once-daily dosing than with twice-daily dosing. Conclusions. Lower pill burden was associated with both better adherence and virological suppression. Adherence, but not virological suppression, was slightly better with once- vs twice-daily regimens.
Abstract
Background
Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited.
...Methods
We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges NSO, low-flow oxygen LFO, high-flow oxygen/noninvasive ventilation HFO/NIV, and invasive mechanical ventilation/extracorporeal membrane oxygenation IMV/ECMO) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial ACTT-1 study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO.
Results
A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio 95% confidence interval: 0.76 0.70–0.83) and 28 days (0.89 0.82–0.96). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 0.57–0.83, LFO: 0.68 0.80–0.77, IMV/ECMO: 0.70 0.58–0.84) and 28 days (NSO: 0.80 0.68–0.94, LFO: 0.77 0.68–0.86, IMV/ECMO: 0.81 0.69–0.94). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 0.70–0.93) but no statistical significance at 28 days.
Conclusions
RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.
Patients treated with remdesivir had a significantly lower risk of mortality compared with those not treated with remdesivir. Consistent with other studies, this large study of US clinical practice supports remdesivir as a treatment option for appropriate COVID-19 patients.
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