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When they analyzed the outcome of an external quality assessment challenge, it turned out that quantitative results deviate in 7.7% of cases by more than ±4 cycles (up to 18 cycles) from the respective individual means, leading to the conclusion that standardization is needed, if patient management procedures should be based on SARS-CoV-2 (RT) PCR Ct-values. [...]a recent study from Switzerland demonstrated that a number of further environmental factors, such as air–liquid interface, contact and temperature difference, are further important factors for successful SARS-CoV-2 replication in cell culture, leading to the conclusion that we still cannot rely on Ct-values as a marker for infectiousness [18]. [...]Kujawski and coworkers were also able to isolate a culturable virus from samples with higher Ct-values (>30) [12], suggesting that theoretically even small amounts of infectious particles might be enough to initiate an infection in vivo as long as no reliable data on the necessary minimum infective dose exists. The use of RATs is increasingly popular and some countries have discussed the easing of pandemic-related restrictions or exemptions from hygiene measures based on negative test results, but it must be emphasized that there is no data supporting the conclusion that an individual with a negative rapid antigen test cannot be infectious.

A phase I study of passive immunization with a CD4 binding-site-directed broadly neutralizing antibody shows that it transiently reduces HIV-1 viral loads in humans. Anti-HIV antibody shows promise The passive administration of broadly neutralizing antibodies (bNAbs) to HIV has been effective against HIV-1 infection in humanized mice and macaque models of HIV-1 infection. It has been suggested that bNAbs, administered passively or by viral vectors, may be effective for prevention and immunotherapy in humans. The safety and efficacy of the approach had not been tested in humans previously but here Michel Nussenzweig and colleagues report the results of a phase I study of passive immunization with neutralizing antibodies directed at CD4 binding sites, and show that the treatment transiently reduces HIV viral loads in humans. HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned 1 , 2 , 3 . However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4 , 5 ). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated 6 , 7 , 8 , 9 , 10 . Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody 11 , in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg −1 infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8–2.5 log 10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

Health workers (HW) are at increased risk for SARS-CoV-2 infection. In order to monitor the infection dynamic on the basis of contact with patients, HW at the St. Antonius Hospital (SAH) were tested four times in one year by PCR and serology. The cumulative incidence of infection in HW was calculated. Swab and blood tests were simultaneously performed between April 2020 and April 2021. Risk factors and demographic information were assessed at the beginning of the study. The response rate was above 75% in all rounds of testing. The study comprised 1506 HW, 165 (10.6%) of which tested positive for SARS-CoV-2 infection. Working in an ICU or on wards with patient contact were risk factors (OR 4.4, 95% CI 1.73–13.6 and OR 2.9, 95% CI 1.27–8.49). At the end of the study, the majority of HW (810 of 1363 (59.4%)) had been vaccinated at least once. A total of 29.1% of unvaccinated HW and 5.3% of vaccinated HW showed an immune response typical for natural SARS-CoV-2 infection. Of the 73 HW who provided information on the course of the disease, 31.5% reported that their quality of life continued to be impaired. The cumulative incidence of infection was low in these HW, which may be attributed to vaccination and good hygiene. Nevertheless, a work-related infection risk was identified, highlighting the need to improve protection against infection. A high risk of developing long COVID was found after the infection has subsided. Special rehabilitation programs should be provided and HW should be compensated for reduced work capacity in the case that rehabilitation fails or takes a long time.

PurposeThe aim of the study was to assess guideline adherence to combined antiretroviral therapy (ART) in the German ClinSurv HIV Cohort and the real-life impact of the Strategic Timing of Antiretroviral Therapy (START) study, to identify patients not treated as recommended by new guidelines.MethodsWe used data from the multicenter ClinSurv cohort of the Robert-Koch-Institute (RKI) between 1999 and 2016. Inclusion criteria were people living with HIV/AIDS, ≥ 18 years of age and cART naïve at the first visit (FV). Adherence was defined as starting cART within 6 months of crossing the CD4+ T cell threshold as suggested by the German-Austrian treatment guidelines. Logistic regression was used to identify factors associated with non-adherence.Results11,817 patients met the inclusion criteria. We observed an overall adherence rate of 60%, in patients with treatment indication who started cART timely between 2002 and 2015. Adherence rate increased constantly, demonstrating a potential increase in patients, with treatment indication, starting cART within 6 months of presentation from 55% in 2008 to 94% in 2015. Patients reporting injection drug use (OR 2.18, 95% CI 1.70–2.95) and patients between 18 years and 39 years of age at the time of their first visit (OR 2.89, 95% CI 1.35–6.18) were identified as risk groups associated with non-adherence.ConclusionThe majority of patients below the CD4+ T cell count threshold of applicable guidelines initiated treatment within 6 months. We observed a slowly diminishing proportion of patients not starting cART timely. Delayed treatment was more frequent in patients reporting injection drug use.

ObjectiveCombination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.MethodsWe analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.ResultsWe included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).ConclusionsDrug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

In this article the cooperating partners of the ClinSurv HIV cohort were not listed in the acknowledgements. The correct paragraph appears below.

Nature 522, 487–491 (2015); doi:10.1038/nature14411 In this Letter, the grant U19AI111825-01 Cooperative Centers on Human Immunology from NIH was erroneously included in the Acknowledgments section; this has been corrected in the online versions of the paper.