Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort.

OBJECTIVES: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. METHODS: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. RESULTS: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. CONCLUSIONS: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses.

The standard regimen of the BNT162b2 mRNA vaccine for SARS-CoV-2 includes two doses administered three weeks apart. However, some public health authorities spaced these doses, raising questions about efficacy. We analyzed longitudinal humoral responses against the D614G strain and variants of concern for SARS-CoV-2 in a cohort of SARS-CoV-2-naive and previously infected individuals who received the BNT162b2 mRNA vaccine with sixteen weeks between doses. While administering a second dose to previously infected individuals did not significantly improve humoral responses, these responses significantly increased in naive individuals after a 16-week spaced second dose, achieving similar levels as in previously infected individuals. Comparing these responses to those elicited in individuals receiving a short (4-week) dose interval showed that a 16-week interval induced more robust responses among naive vaccinees. These findings suggest that a longer interval between vaccine doses does not compromise efficacy and may allow greater flexibility in vaccine administration.

Sensitivity of SARS-CoV-2 Detection With Nasopharyngeal Swabs.

Background: SARS-CoV-2-infected subjects have been proven contagious in the symptomatic, pre-symptomatic and asymptomatic phase. The identification of these patients is crucial in order to prevent virus circulation. No reliable data on the sensitivity of nasopharyngeal swabs (NPS) are available because of the lack of a shared reference standard to identify SARS-CoV-2 infected patients. The aim of our study was to collect data on patients with a known diagnosis of COVID-19 who underwent serial testing to assess NPS sensitivity. Methods: The study was a multi-center, observational, retrospective clinical study with consecutive enrollment. We enrolled patients who met all of the following inclusion criteria: clinical recovery, documented SARS-CoV-2 infection (≥1 positive rRT-PCR result) and ≥1 positive NPS among the first two follow-up swabs. A positive NPS not preceded by a negative nasopharyngeal swab collected 24-48 h earlier was considered a true positive. A negative NPS followed by a positive NPS collected 24-48 h later was regarded as a false negative. The primary outcome was to define sensitivity of SARS-CoV-2 detection with NPS. Results: Three hundred and ninety three NPS were evaluated in 233 patients; the sensitivity was 77% (95% CI, 73 to 81%). Sensitivity of the first follow-up NPS (n = 233) was 79% (95% CI, 73 to 84%) with no significant variations over time. We found no statistically significant differences in the sensitivity of the first follow-up NPS according to time since symptom onset, age, sex, number of comorbidities, and onset symptoms. Conclusions: NPS utility in the diagnostic algorithm of COVID-19 should be reconsidered.