Survey of physician knowledge regarding antiretroviral medications in hospitalized HIV-infected patients

<p>Abstract</p> <p>Background</p> <p>Antiretroviral prescribing errors are common among hospitalized patients. Inadequate medical knowledge is likely one of the factors leading to these errors. Our objective was to determine the proportion of hospital physicians with knowledge gaps about prescribing antiretroviral medications for hospitalized HIV-infected patients and to correlate knowledge with length and type of medical training and experience.</p> <p>Methods</p> <p>We conducted an electronic survey comprising of ten clinical scenarios based on antiretroviral-prescribing errors seen at two community teaching hospitals. It also contained demographic questions regarding length and type of medical training and antiretroviral prescribing experience. Three hundred and forty three physicians at both hospitals were asked to anonymously complete the survey between February 2007 and April 2007.</p> <p>Results</p> <p>One hundred and fifty-seven physicians (46%) completed at least one question. The mean percentage of correct responses was 33% for resident physicians, 37% for attending physicians, and 93% for Infectious Diseases or HIV (ID/HIV) specialist physicians. Higher scores were independently associated with ID/HIV specialty, number of outpatients seen per month and physician reported comfort level in managing HIV patients (P < .001).</p> <p>Conclusion</p> <p>Non-ID/HIV physicians had uniformly poor knowledge of common antiretroviral medication regimens. Involvement of ID/HIV specialists in the prescribing of antiretrovirals in hospitalized patients might mitigate prescribing errors stemming from knowledge deficits.</p

Tocilizumab in patients hospitalised with COVID-19 pneumonia: efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)

Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C

Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults Previously Vaccinated With Pneumococcal Polysaccharide Vaccine

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk of pneumococcal disease. We evaluated the safety and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) in this population. METHODS: HIV-infected persons ≥ 18 years of age who were previously vaccinated with ≥ 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and had CD4 cell counts ≥ 200 cells/mm(3) and HIV viral loads \u3c50 000 copies/mL were enrolled in this 3-dose PCV13 open-label study. RESULTS: A total of 329 subjects received ≥ 1 dose, and 279 received 3 doses administered at 6-month intervals. Increases in anticapsular polysaccharide immunoglobulin G concentrations and opsonophagocytic antibody titers were demonstrated 1 month after each of the 3 doses of PCV13. Antibody levels were generally similar after each dose. The responses were similar whether subjects had previously received 1 or ≥ 2 doses of PPSV23. Pain at the injection-site was the most common local reaction. Severe injection site or systemic events were uncommon. CONCLUSIONS: Vaccination with PCV13 induces anticapsular immunoglobulin G and opsonophagocytic antibody responses in HIV-infected adults with prior PPSV23 vaccination and CD4 cell counts ≥ 200 cells/mm(3). The observations support the use of PCV13 in this population

Detection of nonnucleoside reverse-transcriptase inhibitor-resistant HIV-1 after discontinuation of virologically suppressive antiretroviral therapy

Using standard and ultrasensitive techniques, we detected nonnucleoside reverse-transcriptase inhibitor-associated resistance mutations in 11 (20%) of 54 subjects who discontinued virologically suppressive nonnucleoside reverse-transcriptase inhibitor-containing antiretroviral therapy. Resistance was detected in 45% and 14% of subjects with a baseline human immunodeficiency virus type 1 RNA level of 51-400 copies/mL an

Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort

OBJECTIVE: Prior studies have shown improved neurocognition with initiation of antiretroviral treatment (ART) in HIV. We hypothesized that stopping ART would be associated with poorer neurocognitive function. METHODS: Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count \u3e350 cells/mm(3), had HIV RNA viral load \u3c55,000 cp/mL, and were on ART (\u3eor=2 drugs) for \u3eor=6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination. RESULTS: A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm(3) and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p \u3c 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed. CONCLUSION: Subjects with preserved immune function found that neurocognition improved significantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration. Classification of evidence: This study provides Class III evidence that discontinuing ART is associated with an improvement in 2 neuropsychological tests (Trail-Making Test A & B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) for up to 96 weeks. Resuming ART was not associated with a decline in these scores for up to 45 weeks

HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers

HIV posttreatment controllers (PTCs) represent a natural model of sustained HIV remission, but they are rare and little is known about their viral reservoir. We obtained 1,450 proviral sequences after near-full-length amplification for 10 PTCs and 16 posttreatment noncontrollers (NCs). Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups. Quantification of total but not intact proviral genome copies predicted sustained HIV remission as 81% of NCs, but none of the PTCs had a total proviral genome greater than 4 copies per million peripheral blood mononuclear cells (PBMCs). The results highlight the restricted intact and defective HIV reservoir in PTCs and suggest that total proviral genome burden could act as the first biomarker for identifying PTCs. Total and defective but not intact proviral copy numbers correlated with levels of cell-associated HIV RNA, activated NK cell percentages, and both HIV-specific CD4+ and CD8+ responses. These results support the concept that defective HIV genomes can lead to viral antigen production and interact with both the innate and adaptive immune systems