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[This corrects the article DOI: 10.1371/journal.pone.0204738.].

In this randomized, controlled trial involving women in South Africa and Uganda, twice-yearly subcutaneous lenacapavir was superior to daily oral emtricitabine–tenofovir disoproxil fumarate in preventing HIV infection.

Hereditary angioedema (HAE) is an autosomal dominant disorder due to deficiency or malfunction of C1 inhibitor protein. It is characterised by recurrent angioedema episodes involving skin and mucosal surfaces. Rare attacks involving upper airway can be life threatening. Attacks are often unpredictable in onset, progression and severity. Deaths resulting from laryngeal angioedema are well recognised. Morbidity and mortality can successfully be reduced with prophylactic C1 esterase inhibitor (C1INH). This requires careful monitoring and individualised therapy. We describe a young girl who presented with recurrent angioedema episodes. The aim is to emphasise that careful monitoring and follow up can significantly influence the quality of care and therapeutic outcomes. She presented multiple times with angioedema involving head and neck region and required multiple paediatric Intensive care unit admissions with potential risk of air way compromise. Her C1 esterase inhibitor protein level was normal with significantly low level of C1 esterase inhibitor functional protein, consistent with type 2 hereditary angioedema. She was initially started on weekly prophylactic C1INH therapy. She continued to have breakthrough angioedema episodes with reduce frequency and severity. A careful review showed that most breakthrough attacks were on day six and day seven since last C1INH therapy. Weekly prophylactic therapy was changed to every 6th day and she was closely followed up. She did not have any breakthrough angioedema episodes on every sixth day C1INH therapy for the following 8 months. C1INH therapy is expensive and may not be available in resource limited centres. We conclude that it is important to make an individualised treatment plan to improve outcome when managing a patient with HAE based on best available sources and considering the needs of the individual patient.Key words:HAE, long term prophylaxis, C1INH.6th day regimen

Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of human immunodeficiency virus (HIV) infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear. In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF). The primary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with the background HIV incidence in the screened population. The secondary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with that in the F/TDF group. Among 3265 participants who were included in the modified intention-to-treat analysis, HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years; 95% confidence interval [CI], 0.01 to 0.37) and in 9 participants in the F/TDF group (0.93 per 100 person-years; 95% CI, 0.43 to 1.77). The background HIV incidence in the screened population (4634 participants) was 2.37 per 100 person-years (95% CI, 1.65 to 3.42). The incidence of HIV infection in the lenacapavir group was significantly lower than both the background incidence (incidence rate ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001) and the incidence in the F/TDF group (incidence rate ratio, 0.11; 95% CI, 0.02 to 0.51; P = 0.002). No safety concerns were identified. A total of 26 of 2183 participants (1.2%) in the lenacapavir group and 3 of 1088 (0.3%) in the F/TDF group discontinued the trial regimen because of injection-site reactions. The HIV incidence with twice-yearly lenacapavir was significantly lower than the background incidence and the incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 2 ClinicalTrials.gov number, NCT04925752.).

In a trial involving infants with grade III, IV, or V vesicoureteral reflux and no previous UTI, continuous antibiotic prophylaxis for 2 years provided a small but significant benefit in preventing a first UTI.

Introduction Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV‐status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV‐specific antibody point‐of‐care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre‐exposure prophylaxis (PrEP) or post‐exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false‐negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. Discussion Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV‐specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource‐limited, high HIV burden settings where HIV‐antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource‐wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. Conclusions With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.

In a double-blind, randomized, placebo-controlled trial in Zimbabwe, treatment of mothers with trimethoprim–sulfamethoxazole daily beginning as early as 14 weeks’ gestation did not significantly increase infant birth weight.

In this double-blind, randomized trial, vancomycin was added to cefazolin as surgical prophylaxis for arthroplasty. Surgical-site infections occurred in 4.5% of vancomycin recipients and 3.5% of placebo recipients.

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Background In the first months after cystectomy, the most frequent cause of readmission is infection from the urinary tract. Nonetheless, current guidelines are unable to provide evidence-based recommendations on preventative measures and, as a result, antibiotic prophylaxis varies across surgical centres. Most centres in Denmark administer empiric antibiotic prophylaxis at ureteral stent removal after cystectomy, where infection rates peak. However, data indicates that the postoperative urinary microbiota is composed of a wide range of bacteria, suggesting that the patients may benefit from an individualised approach. This trial aims to test whether targeted postoperative antibiotic prophylaxis can reduce infection-related readmissions after cystectomy compared to the current empiric approach. Methods We present a multicentre, open-label, superiority, randomised clinical trial using a group-sequential design. Participants will be randomly assigned with a 1:1 allocation ratio to receive one of two orally administered single-day antibiotic treatments on the day of ureteral stent removal: (a) standard-of-care pivmecillinam 400 mg morning, noon, and evening or (b) antibiotics targeted to the microbiota identified in a postoperative urine sample. The primary endpoint is the infection-related readmission rate after 90 postoperative days. Secondary endpoints include complication and readmission rates, days alive and out of hospital, quality of life, and microbiological isolates in the urine and blood and antimicrobial susceptibility analyses. A total of 248 patients are planned to be enrolled. The sample size is based on a hypothesised absolute risk reduction in the infection-related readmission rate from 29 to 14%, corresponding to a number needed to treat of six to reduce one hospital readmission. A group-sequential design is proposed to allow for early stopping at interim analysis after 50% enrolment based on predefined rules. Discussion Responsible use of antibiotics is gaining increasing importance globally, and proper prophylactic strategies amongst high-risk patients are essential to avoid hospital admissions with administration of broad-spectrum agents. In this protocol, we present the first randomised clinical trial testing whether individualised targeted antibiotics can reduce the risk of infections after cystectomy. Results of the trial may improve recovery for this vulnerable patient group, while also potentially improving antibiotic stewardship. Trial registration EU trial number 2024–514312-27–00. Registered on December 10, 2024. ClinicalTrials.gov NCT06709196. Registered on November 27, 2024.