Abstract
Background
People living with HIV (PLWH) are more likely to smoke and harbor oral human papillomavirus (HPV) infections, putting them at higher risk for head and neck cancer. We investigated ...effects of HIV and smoking on oral HPV risk.
Methods
Consecutive PLWH (n = 169) and at-risk HIV-negative individuals (n = 126) were recruited from 2 US health centers. Smoking history was collected using questionnaires. Participants provided oral rinse samples for HPV genotyping. We used multivariable logistic regression models with interaction terms for HIV to test for smoking effect on oral HPV.
Results
PLWH were more likely to harbor oral HPV than HIV-negative individuals, including α (39% vs 28%), β (73% vs 63%), and γ-types (33% vs 20%). HIV infection positively modified the association between smoking and high-risk oral HPV: odds ratios for smoking 3.46 (95% confidence interval CI, 1.01–11.94) and 1.59 (95% CI, .32–8.73) among PLWH and HIV-negative individuals, respectively, and relative excess risk due to interaction (RERI) 3.34 (95% CI, −1.51 to 8.18). RERI for HPV 16 was 1.79 (95% CI, −2.57 to 6.16) and 2.78 for β1-HPV (95% CI, −.08 to 5.65).
Conclusion
Results show tobacco smoking as a risk factor for oral HPV among PLWH.
Our finding that HIV infection modifies the relationship between tobacco smoking, oral HPV infection, and oral cancers is important, as this may have public health implications if high-risk PLWH can be targeted for cancer screening and smoking cessation interventions.
Medical tourism is increasingly popular for elective cosmetic surgical procedures. However, medical tourism has been accompanied by reports of post-surgical infections due to rapidly growing ...mycobacteria (RGM). The authors’ experience working with patients with RGM infections who have returned to the USA after traveling abroad for cosmetic surgical procedures is described here.
Patients who developed RGM infections after undergoing cosmetic surgeries abroad and who presented at the Montefiore Medical Center (Bronx, New York, USA) between August 2015 and June 2016 were identified. A review of patient medical records was performed.
Four patients who presented with culture-proven RGM infections at the sites of recent cosmetic procedures were identified. All patients were treated with a combination of antibiotics and aggressive surgical treatment.
This case series of RGM infections following recent cosmetic surgeries abroad highlights the risks of medical tourism. Close monitoring of affected patients by surgical and infectious disease specialties is necessary, as aggressive surgical debridement combined with appropriate antibiotic regimens is needed to achieve cure. Given the increasing reports of post-surgical RGM infections, consultants should have a low threshold for suspecting RGM, as rapid diagnosis may accelerate the initiation of targeted treatment and minimize morbidity.
We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 human immunodeficiency virus (HIV)-positive patients and 128 HIV-negative patients ...presenting for oral examination at 2 urban healthcare centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV DNA typing by polymerase chain reaction. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive patients and HIV-negative patients, respectively, including high-risk HPV type 16 (8% and 2%, respectively; P = .049) and uncommon HPV types 32/42 (6% and 5%, respectively; P = .715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sex partners (≥; 21 vs≤5; odds ratio OR, 9.1; 95% confidence interval CI, 1.7-49.3), heavy tobacco smoking (> 20 pack-years vs none; OR, 9.2; 95% CI, 1.4-59.4), and marijuana use (OR, 4.0; 95% CI, 1.3-12.4). Among HIV positive patients, lower CD4⁺ T-cell count only was associated with oral HPV detection (≤ 200 vs ≥ 500 cells/mm³; OR, 4.5; 95% CI, 1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions among HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4⁺ T-cell counts.
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.
We conducted a ...double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval CI, 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).
Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Abstract
Background
(1,3)-β-D-glucan (BDG) has been utilized as an indirect marker for Pneumocystis jirovecii pneumonia (PJP). The clinical utility of BDG, however, is limited because of uncertainty ...in interpreting quantitative values. A correlation was drawn between quantitative BDG and the diagnosis of PJP in hospitalized patients living with human immunodeficiency virus (HIV) at four affiliate campuses of the Montefiore Health System in the Bronx, NY.
Methods
All Pneumocystis direct fluorescent assays (DFA), polymerase chain reactions (PCR) either from bronchoalveolar lavage (BAL) fluid or sputum, and quantitative BDG assays either from serum or BAL fluid were retrieved from the Montefiore microbiology laboratory (date range: 8/1/18 - 8/31/22). Results from hospitalized patients with HIV whose CD4 count within 3 months were available, with either PJP DFA or PCR result within 7 days of serum BDG and lactate dehydrogenase (LDH) test were selected (n = 146). CD4 count was grouped into < 50 (n = 106), 50-100 (n = 15), 100-200 (n = 16), and >200 (n = 9). BDG, LDH, and CD4 were considered as input variables in a logistic regression model for true PJP status. The area under the curve (AUC) of the empirical receiver operating characteristic (ROC) curve with 95% confidence intervals (CI) was estimated based on trapezoidal area. Comparisons between ROC curve areas were performed via contrast matrix to take differences of the AUC of the empirical ROC curves and chi-square testing.
Results
Of the 146, 29 had PJP detected and 117 did not. When BDG only was considered, the AUC of the ROC curve was 0.78. When LDH quartiles (cutoffs: 232, 334, and 480 U/L) were considered with BDG, there was a statistically significant increase in AUC (0.84 vs. 0.78; p = 0.025). Adding CD4 group did not influence AUC.
Figure 1
ROC curves for BDG only, BDG with CD4 count, BDG with LDH quartile, and BDG with CD4 group and LDH quartile combined
Table 1
Area under the curve calculated for the ROC curves for BDG only, BDG with CD4 count, BDG with LDH quartile, and BDG with CD4 group and LDH quartile combined
Conclusion
The test characteristics (AUC) improved when LDH quartiles were used in conjunction with BDG, suggesting a better prediction of PJP diagnosis when BDG and LDH were considered together. This result supports further investigation of clinical markers of PJP given the limitations of establishing a microbiologic diagnosis. Further steps of the investigation will involve analyzing if other clinical factors including HIV viral load, oxygen saturation, and radiographical reading, influence predictability of PJP.
Disclosures
All Authors: No reported disclosures
Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon ...beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.
We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475.
Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 95% CI 0·87-1·13; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 95% CI 0·69-2·55; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 7% of 442 patients) than in the placebo plus remdesivir group (15 3% of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group.
Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo.
The National Institute of Allergy and Infectious Diseases (USA).
Pharmacy refill adherence has become an increasingly important measure of adherence to antiretroviral medications. It offers a simple, inexpensive, and valid method for measuring adherence. Over the ...past year, there have been several published developments in the use of pharmacy refill data to measure adherence. Given the utility of this adherence measurement, it is likely that pharmacy refill will be the method of choice for measuring antiretroviral adherence in an increasing number of clinical and research settings.
The goal of this study was to determine the validity and utility of a pharmacy-based time-to-refill measure of antiretroviral therapy adherence.
We performed an observational cohort study of 110 ...HIV-infected subjects on a stable, highly active antiretroviral regimen for at least 3 months at a Veterans' Affairs Medical Center in Philadelphia, Pennsylvania.
The viral load decreased by 0.12 log c/mL (95% confidence interval CI 0.01–0.23 log c/mL) for each 10% increase in pharmacy-based time-to-refill defined adherence as compared with 0.05 log c/mL (95% CI −0.14–0.25 log c/mL) for the self-reported adherence measure. Thus, only the refill-defined measure was statistically significantly associated with viral load change. When adherence was classified as good (≥85%) versus poor (<85%), both measures demonstrated a significant difference in outcome between groups. Yet, in individuals self-reporting 100% adherence, those classified as good adherers using the pharmacy-based measure had greater viral load reductions than poor adherers (2.4 log c/mL interquartile range 1.4–3.4 vs. 1.5 log c/mL interquartile range 0.8–2.4,
P
=
.03).
The pharmacy-based technique is a valid measure of antiretroviral therapy adherence. Because it provides clinically relevant information in subjects who self-report 100% adherence, it should be incorporated into clinical practice and adherence research.
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