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Clinical trial study protocol

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEP) to HIV following sexual exposures, occupational exposures and other nonoccupational exposures in the community. This serves as an update to the 2015 BASHH guideline on PEP following sexual exposures and the 2008 Expert Advisory Group on AIDS guidelines on HIV PEP. We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of PEP for the prevention of HIV acquisition following sexual, occupational and other nonoccupational exposures in the community. The guideline covers when to prescribe PEP, what antiretroviral agents to use and how to manage PEP. This includes (i) evidence of PEP efficacy; (ii) evidence relating to individual-level efficacy of antiretroviral therapy to prevent the sexual transmission of HIV; (iii) data on the detectable (transmissible) prevalence of HIV in specific populations; (iv) risk of HIV transmission following different types of sexual and occupational exposure; (v) baseline risk assessment; (vi) drug regimens and dosing schedules; (vii) monitoring PEP; (viii) baseline and follow-up blood-borne virus testing; (ix) the role of PEP within broader HIV prevention strategies, for example, HIV pre-exposure prophylaxis (PrEP). The guideline also covers special scenarios such as PEP in pregnancy, breastfeeding and chronic hepatitis B virus infection, and when PEP should be considered in people using HIV PrEP. The guidelines are aimed at clinical professionals directly involved in PEP provision and other stakeholders in the field. A proforma to assist PEP consultations is included. A public consultation process was undertaken prior to finalizing the recommendations.

Background\ud An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) prior to presentation. There is some evidence suggesting an increased two-week mortality in those receiving ART for less than 14 days compared with those on ART for more than 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or non-adherence are not well described.\ud \ud Methods\ud 678 adults with first episode of cryptococcal meningitis recruited into a randomized, non-inferiority, multicentre phase 3 trial in 4 sub-Saharan countries were analysed to compare clinical presentation and 2-and 10-week mortality outcomes between ART-naive and experienced patients, and between patients receiving ART for varying durations prior to presentation.\ud \ud Results\ud Over half (56% (381/678)) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2-weeks (17% vs 20%; HR 0.85, 95%CI 0.6-1.2, p=0.35), and 10 weeks (38% vs 36%; HR 1.03, 95%CI 0.8-1.32, p=0.82) for ART-experienced vs ART-naïve patients, respectively. Among ART-experienced patients, using different cut-off points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART.\ud \ud Conclusion\ud In this study, there were no significant differences in mortality at 2-and 10-weeks between ART- naive and experienced patients, and between ART-experienced patients according to duration on ART.

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus .\ud \ud Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.\ud \ud Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.\ud \ud Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at 48 h following hospital admission, corresponding to community and hospital-acquired co-infections.\ud \ud Results. Of 254 patients studied (median age 59 years (IQR 49–69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli . The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3–34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03–3.08, P=0.04) compared to those without co-infections/ co-colonisation.\ud \ud Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.

Background: HIV-associated cryptococcal meningitis accounts for 15% of AIDS related deaths globally. In sub-Saharan Africa, acute mortality ranges from 24% to 100%. In addition to the mortality directly associated with cryptococcosis, patients with HIV-associated cryptococcal meningitis are at risk of a range of opportunistic infections (OIs) and hospital acquired nosocomial infections (HAIs). The attributable mortality associated with co-prevalent infections in cryptococcal meningitis has not been evaluated.\ud \ud Methods: As part of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) trial, consecutive HIV-positive adults with cryptococcal meningitis were randomised to one of five anti-fungal regimens and followed up until 10-weeks. We conducted a retrospective case note review of ACTA participants recruited from Queen Elizabeth Central Hospital in Blantyre, Malawi to describe the range and prevalence of OIs and HAIs diagnosed, and the attributable mortality associated with these infections.\ud \ud Results: We describe the prevalence of OIs and HAIs in 226 participants. Baseline median CD4 count was 29 cell/mm3, 57% (129/226) were on anti-retroviral therapy. 56% (127/226) had at least one co-prevalent infection during the 10-week study period. Data were collected for 187 co-prevalent infection episodes. Suspected blood stream infection was the commonest co-prevalent infection diagnosed (34/187, 18%), followed by community-acquired pneumonia (32/187, 17%), hospital-acquired pneumonia (13/187, 7%), pulmonary tuberculosis (12/187, 6%) and confirmed blood stream infections (10/187, 5%). All-cause mortality at 10-weeks was 35% (80/226), diagnosis of an OI or HAI increased the risk of death at 10 weeks by nearly 50% (HR 1.48, 95% CI 1.01-2.17, p=0.04).\ud \ud Conclusion: We demonstrate the high prevalence and broad range of OIs and HAIs occurring in patients with HIV-associated cryptococcal meningitis. These co-prevalent infections are associated with a significantly increased risk of death. Whether a protocolised approach to improve surveillance and proactive treatment of co-prevalent infections would improve cryptococcal meningitis outcomes warrants further investigation.