Trend over time of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and their drivers: A cohort study from Antiviral Response Cohort Analysis (ARCA).

The rise of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) threatens the long-term success of NNRTI-based therapies. Our study aims to describe the circulation of major resistance-associated mutations (RAMs) for NNRTIs in people living with HIV (PLWH) in Italy from 2000 to 2020. We included 5982 naïves and 28 505 genotypes from 9387 treatment-experienced PLWH from the Antiviral Response Cohort Analysis (ARCA) cohort. Transmitted drug resistance (TDR) was found in 12.5% and declined from 17.3% in 2000-2003 to 10.9% in 2016-2020 (p = 0.003). Predictors of TDR were viral subtype B [vs. non-B, adjusted odds ratio (aOR) = 1.94, p < 0.001], zenith viral load (VL) (per 1 log10 higher, aOR = 0.86, p = 0.013), nadir CD4 cell count (per 100 cells/µL increase aOR = 0.95, p = 0.013). At least one RAM for NNRTIs among treatment experienced PLWH was detected in 33.2% and pre-treatment drug resistance (PDR) declined from 43.4% in 2000-2003 to 20.9% in 2016-2020 (p < 0.001). Predictors of PDR were sexual transmission route (vs. others, aOR = 0.78, p < 0.001), time since HIV diagnosis (per 1 month longer, aOR = 1.002, p < 0.001), viral subtype B (vs. non B, aOR = 1.37, p < 0.001), VL (per 1 log10 higher, aOR = 1.12, p < 0.001), nadir CD4 count (per 100 cells/µL increase, aOR = 0.91, p < 0.001), previous exposure to any NNRTI (aOR = 2.31, p < 0.001) and a more recent calendar year sequence (any time span > 2008 vs. 2000-2003, any aOR <1, p < 0.001). Circulation of RAMs to NNRTIs declined during the last 20 years in Italy. NNRTIs remain pivotal drugs for the management of HIV-1 due to safety concerns and long-acting options.

Disseminated Mycobacterium chimaera infection favoring the development of Kaposi's sarcoma: a case report.

BACKGROUND: Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations. CASE PRESENTATION: We report the case of a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi's sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks. CONCLUSIONS: M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi's sarcoma) cannot be excluded.

One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.

Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.

Increasing incidence and prevalence of metabolic syndrome in people living with HIV during the COVID-19 pandemic.

Introduction: The aim of this study was to analyze the impact of COVID-19 pandemic restrictions on the prevalence and incidence of metabolic syndrome (MS), and to identify predictors of new MS cases in people living with HIV (PLWH). Methods: This cohort study included PLWH followed at the IRCCS San Raffaele, Milan, Italy, with at least one body mass index (BMI) determination during the pre-pandemic period (1 December 2018 to 29 February 2020) and the pandemic period (1 March 2020 to 31 May 2021). MS diagnosis was based on NCEP ATP III 2005 criteria. Univariable Poisson regression model was used to compare MS incidence rates. Univariable mixed linear models estimated the crude mean change in metabolic parameters during each time period. Multivariable Cox proportional hazards model was used to assess risk factors for MS. Results: This study included 1,564 PLWH, of whom 460 and 1,104 were with and without a diagnosis of MS, respectively, at the beginning of the pre-pandemic period, with an overall prevalence of MS of 29.4%. During the pre-pandemic period, 528/1,564 PLWH had MS, with a prevalence of 33.8% (95%CI = 31.5%-36.1%), while during the pandemic period, the number of PLWH with a diagnosis of MS increased to 628/1,564, with a prevalence of 40.2% (95%CI 37.8%-42.6%; McNemar's test: p < 0.0001). Similarly, the MS incidence rate increased from 13.7/100 person-years of follow-up (PYFU; 95%CI = 11.7-16.0) in the pre-pandemic period to 18.5/100 PYFU (95%CI = 16.2-21.1) in the pandemic period (p = 0.004), with 201 subjects developing MS during the pandemic period. In addition, we observed a significant increase in the crude mean change during the pandemic period compared with the pre-pandemic period for: total cholesterol, LDL cholesterol, plasma glucose, blood pressure, and atherosclerotic cardiovascular disease (ASCVD) risk score. Finally, after adjustment for HIV risk factors, HBV, HCV, ART duration, duration of virologic suppression and use of INSTIs, age [adjusted hazard ratio (AHR) per 3 years older = 1.12 (95%CI = 1.08-1.17)], sex [AHR female vs. male = 0.62 (95%CI = 0.44-0.87)] and CD4+ cell count [AHR per 100 cells/µL higher = 1.05 (95%CI = 1.01-1.09)] were associated with the risk of MS. Conclusion: The COVID-19 pandemic affected the metabolic profile of PLWH and increased the prevalence and incidence of MS.