Associations between antiretroviral regimen and changes in blood pressure: results from the D2EFT study.

In this randomised, controlled study in 14 low- and middle-income countries, individuals taking dolutegravir with darunavir/ritonavir for 48 weeks had a greater increase in systolic and diastolic blood pressure than individuals taking two nucleoside reverse transcriptase with darunavir/ritonavir. The difference remained significant after controlling for confounding factors including weight gain.

Characteristics of Human Immunodeficiency Virus (HIV) Seroconversions in a Large Prospective Implementation Cohort Study of Oral HIV Preexposure Prophylaxis in Men Who Have Sex with Men (EPIC-NSW).

BACKGROUND: Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. RESULTS: A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25-38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347-656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. CONCLUSIONS: Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Disseminated Aspergillus lentulus Infection in a Heart Transplant Recipient: A Case Report.

We present the first published case of successfully treated disseminated Aspergillus lentulus infection in a solid organ transplant recipient with invasive pulmonary disease, endophthalmitis, and a cerebral abscess. This case highlights important challenges associated with treating A. lentulus, particularly regarding antifungal resistance and toxicities associated with long-term antifungal therapy.

Low Prior Exposure and Incidence of Hepatitis C in Human Immunodeficiency Virus-Negative Gay and Bisexual Men Taking Preexposure Prophylaxis (PrEP): Findings From the Expanded PrEP Implementation in Communities-New South Wales Prospective Implementation Study.

BACKGROUND: The use of preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has raised concerns of increased sexual risk behaviors. These behaviors may be associated with increased incidence of sexually acquired hepatitis C virus (HCV) among gay and bisexual men. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study was a cohort study of daily coformulated tenofovir disoproxil fumarate and emtricitabine for HIV prevention. We recruited 9596 people at high risk of HIV acquisition from 31 clinics across New South Wales and the Australia Capital Territory in Australia. We report prior exposure to HCV and incidence in this cohort between 2016 and 2019. RESULTS: At least 1 HCV test result was available for 8658 (90.2%) participants. These individuals had a median age of 34 years (interquartile range, 28-43), most of whom were male (8530, 98.5%), identified as gay (7944, 91.8%), and were born in Australia (51.8%). Prior exposure to HCV was detected among 81 participants at baseline (0.9%; 95% confidence interval [CI]: .71.2). Twenty of 8577 participants were diagnosed with incident infection (rate 0.2/100 person-years [95% CI: .1-.3/100 person-years]). They were significantly older (median age 41 years vs 34 years, P = .044), and more likely to report methamphetamine use at baseline (incidence rate ratio, 2.7 [95% CI: 1.00-7.2]) than those without incident infection. CONCLUSIONS: In this population of PrEP users, HCV prior exposure and incidence were low. With high levels of HCV and HIV testing and treatment, the dual goals of HIV and HCV elimination could be achieved in this population. Clinical Trials Registration: number NCT02870790.

Multispecies Outbreak of Nocardia Infections in Heart Transplant Recipients and Association with Climate Conditions, Australia.

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018-2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015-March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018-2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018-2019, may explain this outbreak of Nocardia infections in HTR.

Overcoming barriers to HIV pre-exposure prophylaxis (PrEP) coverage in Australia among Medicare-ineligible people at risk of HIV: results from the MI-EPIC clinical trial.

Background Overseas-born people who are ineligible for government-subsidised health care experience barriers to accessing HIV pre-exposure prophylaxis (PrEP) in Australia. This study aimed to assess a program providing free PrEP to overseas-born adults at risk of acquiring HIV. Methods Medicare-Ineligible Expanded Implementation in Communities (MI-EPIC) was a single-arm, open-label trial of daily tenofovir disoproxil fumarate/emtricitabine as PrEP. Six clinics recruited Medicare-ineligible adults who met HIV risk criteria in New South Wales, Australia. We recorded data on HIV and sexually transmitted infection (STI) diagnoses, and PrEP dispensing from July 2019 to June 2020. PrEP adherence as a medication possession ratio (MPR) was calculated as pills dispensed divided by days. We administered an optional survey on behaviours and attitudes to PrEP and sexual health. Results The 221 participants (206 men; 93.2%) had a median age of 29years (IQR 26-34). Participants were mostly born in Asia (53.4%), Latin America or the Caribbean (25.3%), or Europe (10.9%). Adherence was high; 190 participants (86.0%) had an MPR of >60%. Of 121 survey participants, 42 (34.7%) completed the survey in a language other than English. Of participants who had not used PrEP in the 6months before enrolment (n=45, 37.2%), the most common reasons were cost (n=22, 48.9%), and lack of knowledge about accessing PrEP (n=20, 44.4%). Conclusions Medicare-ineligible people at risk of HIV demonstrate high adherence when given access to free PrEP and translated information. Increasing PrEP awareness and reducing barriers to accessing PrEP in this high-risk population should be priorities in HIV prevention.

Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy.

BACKGROUND: Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART). METHODS: A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock. RESULTS: There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of <0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration. CONCLUSIONS: PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.

DNA methylation is associated with airflow obstruction in patients living with HIV.

INTRODUCTION: People living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH. METHODS: Using blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV1, FEV1/FVC ratio and FEV1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing. RESULTS: Airflow obstruction as defined by a FEV1/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV1/FVC

Colonic malakoplakia in a dual stem cell and cardiac transplant recipient: A case report and literature review.

We describe the first published case of malakoplakia in a dual stem cell and cardiac transplant recipient. In the 2 months following cardiac transplantation, our patient developed persistent diarrhea and recurrent E coli bacteremia. Biopsies obtained from areas of colonic thickening revealed malakoplakia. Despite improvement in symptoms with prolonged antimicrobial therapy and reduction of his immunosuppression, he eventually died from sepsis. Our case highlights not only the importance of the timely diagnosis of this rare disorder, but also the difficulty in determining optimal treatment duration, particularly where excision of involved areas is not possible, as data on this disease are lacking. Here we describe our case and review the available literature published on malakoplakia in the cardiac transplant population.

Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis.

BACKGROUND: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid. METHODS: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions. RESULTS: Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 µg per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 µg per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 µg per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater. CONCLUSIONS: This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).

Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial.

The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm). The following outcomes were evaluated: fibrosis (APRI > 0.5 or FIB-4 > 1.45), significant fibrosis (APRI > 1.5 or FIB-4 > 3.25), hepatic flare, and resolution of elevated APRI and FIB-4 scores. Of the 4,684 enrolled into the START study, 104 did not have APRI or FIB-4 results and were excluded. Among 4,580 participants (2,273 immediate treatment; 2,307 deferred treatment), the median age was 36 years, 26.9% were female, and 30.4% were black. Three percent had an alcoholism or substance abuse history, 6.4% had hepatitis B and/or C, and 1.1% had significant fibrosis at baseline. The median CD4 count was 651, and 5.3% had HIV RNA ≤ 200. Immediate arm participants were at lower risk of developing increased fibrosis scores than deferred arm participants (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.57-0.78; P < 0.001) and more likely to have resolution of elevated baseline scores (HR 1.6; 95% CI 1.3-1.9; P < 0.001). Conclusions: Significant liver fibrosis was rare among ART-naïve HIV-positive persons with high CD4 counts. Our findings suggest a benefit of early ART in preventing the development of liver fibrosis.

HIV treatment regimens and adherence to national guidelines in Australia: an analysis of dispensing data from the Australian pharmaceutical benefits scheme.

BACKGROUND: Treatment guidelines for antiretroviral therapy (ART) have evolved to emphasize newer regimens that address ageing-related comorbidities. Using national Australian dispensing data we compare ART regimens with Australian HIV treatment guidelines in the context of treated comorbidities. METHODS: The study population included all individuals in a 10% sample of national data from the Australian Pharmaceutical Benefits Scheme (PBS) who purchased a prescription of ART during 2016. We defined each patient's most recently dispensed ART regimen and characterized them to evaluate regimen complexity and adherence to national HIV treatment guidelines. We then analyzed ART regimens in the context of other co-prescriptions purchased for defined comorbidities. RESULTS: The 1995 patients in our sample purchased 212 different ART regimens during 2016; 1524 (76.4%) purchased one of the top ten most common regimens of which 62.3% were integrase strand transfer inhibitor-based. Among the 1786 (90%) patients that purchased the most common regimens, 83.7% purchased a regimen recommended by the guidelines for initial antiretroviral therapy and 11.4% purchased antiretrovirals that are not recommended for initial therapy; < 1% of the entire cohort purchased medications not recommended for use. While most patients purchased optimal ART regimens with low potential for significant drug interactions, regimen choices in the setting of risk factors for heart disease, renal disease and low bone mineral density appeared suboptimal. CONCLUSIONS: Australian HIV providers are prescribing ART regimens in accordance with updated treatment guidelines, but could further optimize regimens in the setting of important medical comorbidities.

Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.

BACKGROUND: The Xpert® MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software. METHODS: An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced. RESULTS: Among 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%-95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%-99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively). CONCLUSIONS: The updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results.

Improving the sensitivity of the Xpert MTB/RIF assay on sputum pellets by decreasing the amount of added sample reagent: a laboratory and clinical evaluation.

The Xpert MTB/RIF (Xpert) assay permits rapid near-patient detection of Mycobacterium tuberculosis in sputum; however, the test sensitivity remains suboptimal in paucibacillary specimens that are negative for acid-fast bacilli using smear microscopy. Xpert testing includes dilution with sample reagent, and when processed sputum pellets are tested, the recommended sample reagent/pellet ratio is 3:1. We evaluated whether a decreased sample reagent/pellet ratio of 2:1 increased Xpert sensitivity compared to the recommended 3:1. The limit of detection was determined by inoculating serial dilutions of M. tuberculosis into sputum samples, preparing sputum pellets, and testing each pellet by Xpert at both sample reagent ratios. Processed sputum pellets obtained from M. tuberculosis culture-positive clinical specimens were also tested by Xpert at both ratios. Among spiked sputum pellets, the limit of detection was 1,478 CFU/ml (95% confidence interval [CI], 1,211 to 1,943) at a 3:1 ratio and decreased to 832 CFU/ml (95% CI, 671 to 1,134) at 2:1. The proportion of specimens in which M. tuberculosis was detected was greater at 2:1 than at 3:1 for almost all numbers of CFU/ml; this difference was most prominent at lower numbers of CFU/ml. Among 134 concentrated sputum pellets from the clinical study, the sensitivity of Xpert at 2:1 was greater than at 3:1 overall (80% versus 72%; P=0.03) and for smear-negative specimens (67% versus 58%; P=0.12). For Xpert testing of sputum pellets, using a lower sample reagent/pellet ratio increased M. tuberculosis detection, especially for paucibacillary specimens. Our study supports use of a 2:1 sample reagent/pellet dilution for Xpert testing of sputum pellets.

Polymicrobial arcanobacterium haemolyticum intracerebral abscess: A case report and review of the literature.

Objective: This article describes a case of polymicrobial Arcanobacterium haemolyticum pharyngitis and sinusitis complicated by intracranial complications and reviews similar cases in the literature. Case summary: A 21-year-old immunocompetent male presented with symptoms of sore throat, rhinorrhoea, lethargy, headache, and rash. Imaging demonstrated sinusitis, pre-septal sinusitis, peritonsillar abscess formation, subdural empyema and cerebritis. He was managed with endoscopic sinus surgery, craniotomy for evacuation of subdural empyema and antibiotics. Microbiological samples demonstrated growth of A. haemolyticum, strep. anginosus, and fusobacterium necrophorum. He subsequently developed a cerebral abscess requiring stereotactic needle drainage. After a prolonged course of antibiotics, the patient was discharge and made a good recovery. Discussion: A. haemolyticum is an uncommon cause of non-streptococcal pharyngitis that may occur alongside other microorganisms and is rarely associated with severe intracranial complications. This organism and its antibiotic susceptibility patterns should be considered in complicated upper respiratory tract infections in immunocompetent hosts. Penicillins and macrolide antibiotics form the mainstay of therapy for A. haemolyticum.

Clinical and laboratory features of COVID-19 illness and outcomes in immunocompromised individuals during the first pandemic wave in Sydney, Australia.

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March-October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n = 12), secondary immunosuppression (N = 8) and those with primary or acquired immunodeficiency (i.e. HIV; N = 7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.

The relationship between the epigenetic aging biomarker "grimage" and lung function in both the airway and blood of people living with HIV: An observational cohort study.

BACKGROUND: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH. METHODS: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV1/FVC<0.70, and FEV1 decline over 6 years in blood. FINDINGS: The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV1/FVC

High Levels of Prevention-Effective Adherence to HIV PrEP: An Analysis of Substudy Data From the EPIC-NSW Trial.

BACKGROUND: Preexposure prophylaxis (PrEP) prevents HIV infection but relies on good adherence at times of risk, termed "prevention-effective adherence." Most studies assess adherence without reference to sexual behaviur, making it challenging to determine if poor adherence coincides with HIV risk. SETTING: We examined data from a behavioral substudy of a large-scale PrEP implementation trial in New South Wales, Australia. METHODS: Trial participants completed optional brief quarterly surveys, reporting the number of pills taken and sexual behavior with male partners for each day of the "last full week" before each survey. Condomless sex (CLS) was defined as "higher risk" for HIV when with HIV-positive men with detectable/unknown viral loads or unknown HIV status men. Adequate PrEP protection was defined as ≥4 pills for participants assigned male sex at birth and ≥6 pills for participants assigned female sex at birth (including transgender men). RESULTS: Of 9596 participants dispensed PrEP, 4401 completed baseline and ≥1 follow-up survey. Participants reported on 12,399 "last full weeks": 7485 weeks (60.4%) involved CLS and 2521 weeks (33.7% of CLS-weeks) involved higher risk CLS. There were 103 weeks in which participants did not have adequate PrEP protection and had higher risk CLS: 4.1% of higher-risk CLS weeks (n = 103/2521), 1.4% of all CLS weeks (n = 103/7485), and 0.8% of all observed weeks (n = 103/12,399). CONCLUSIONS: In a large PrEP trial, prevention-effective adherence to PrEP was very high at 99%. Our findings illustrate the importance of measuring pill-taking and sexual behavior in the same period so that prevention-effective adherence can be better estimated.