Weight Gain in Overweight and Obese People with HIV-The OBHIV Cohort.

BACKGROUND: HIV and non-HIV-related factors have been related to weight gain (WG); however, their specific impact on people with HIV (PWH) who are overweight or obese remains unclear. METHODS: This is a single-center observational study enrolling PWH with a BMI > 25 kg/m2. A generalized linear model was used to assess variables related to greater WG during 12 years of observation. RESULTS: A total of 321 PWH were enrolled, 67% overweight and 33% obese, who gained an average of 0.2 ± 1.3 and 1.7 ± 1.5 kg/year, respectively (p < 0.0001). Years since HIV infection were the only variable significantly associated with WG (ß -0.048, 95% CI -0.083; -0.013) during the study period, while type of ART did not influence the outcome. Narrowing the observation to the period of the SARS-CoV-2 pandemic, PWH with a longer duration of infection (ß 0.075, 95% CI 0.033; 0.117) and a greater increase in triglycerides (ß 0.005; 95% CI 0.000; 0.011) gained more weight, while higher BMI (ß -0.256, 95% CI -0.352; -0.160), obesity (ß -1.363, 95% CI -2.319; -0.408), diabetes mellitus (ß -1.538, 95% CI -2.797; -0.278), and greater abdominal circumference (ß -0.086, 95% CI -0.142; -0.030) resulted in protection. CONCLUSION: Among overweight and obese PWH, the amount of WG was higher in the first years after diagnosis of HIV and decreased thereafter, despite aging, regardless of the type of ART.

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.

Histopathologic and transmission electron microscopic findings in monkeypox cutaneous lesions.

Background: a few pathologic and ultrastructural findings of monkeypox skin lesions are available in the literature. To integrate such evidence, we aimed to describe the pathologic features of monkeypox skin lesions and to show monkeypox virions by transmission electron microscopy (TEM). Methods: we studied the cutaneous biopsies of three patients affected by monkeypox during the 2022 monkeypox outbreak. Skin biopsies have been collected only from body sites with a recent laboratory-confirmed mpox virus infection, defined by a polymerase chain reaction (PCR) positive result in specimens taken through skin swabs. Results: in all the samples the epidermis showed keratinocytes ballooning degeneration; perivascular/periadnexal infiltrates composed of neutrophils and lymphocytes were observed in the deep dermis. Immunohistochemistry showed that the infiltrate was mostly composed of CD3+ T-cells. TEM revealed monkeypox virus-like particles in various stages of morphogenesis in the dermis and epidermis; virions were interspersed among keratinocytes and within their cytoplasm. At the intracellular level, virions showed a biconcaveshaped central core, surrounded by lateral bodies and an external membrane; they also appeared as rectangular, brick-shaped, or oval particles with eccentric nucleoids. The histologic features of our skin samples confirmed the few other studies on this topic, except for the eosinophilic inclusions of the cytoplasm of keratinocytes (Guarnieri's bodies). Conclusion: the role of molecular biology is crucial for monkeypox diagnosis but when it is not disposable and/or in doubtful cases, skin biopsy and TEM may be helpful to establish the diagnosis.

People with HIV pioneers of injectable cabotegravir and rilpivirine long acting in Italy: who are they?

Injectable cabotegravir and rilpivirine long-acting therapy is a revolutionary new antiretroviral treatment (ART) option for HIV infection in virologically suppressed adults on a stable ART. The aim of this study from SCOLTA multicenter observational prospective database is to describe the first people living with HIV (PWH) who started this regimen in Italy, assessing adherence to eligibility criteria, describing clinical-epidemiological characteristics compared to registration trials-population and describe early treatment-discontinuations.

Knowledge of Sexually Transmitted Infections and HIV among People Living with HIV: Should We Be Concerned?

Poor knowledge of sexually transmitted infections (STIs) and HIV among people with HIV (PLHIV) could worsen life quality. We aimed to investigate their STI and HIV knowledge, disclosure and undetectable = untransmittable (U=U). We proposed an anonymous questionnaire regarding STI and HIV to PLHIV attending ten Italian outpatient infectious diseases clinics. Moreover, disclosure and U=U were investigated. The calculated sample size was 178 people. Considering a missing response of 10%, the final sample size was 196. We enrolled 200 PLHIV (73.5% males), with a median age of 52.5 (IQR 41-59) years. The mean score was 7.61 ± 1.22 with no difference by gender, education, and employment. Significant statistical difference was observed by sexual orientation; bisexuals and those who preferred not to answer had a lower score than heterosexuals and MSM (p = 0.0032). PLHIV showed poor knowledge about HIV transmission (25% appropriately answered). Nearly 30% responded that virologically suppressed PLHIV could transmit the infection. Finally, 137 (68.5%) and 158 (79.0%) disclosed to the general practitioner and family and friends, respectively. Nearly 52.0% knew the meaning of U=U, and 83.6% highlighted its positive rebound. In conclusion, important knowledge gaps are present among PLHIV regarding U=U, and its implications are little-known. Improving PLHIVs' awareness will undermine self-stigma and enhance life quality.

Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors.

PURPOSE: The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population. PARTICIPANTS: The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry. FINDINGS TO DATE: The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples. FUTURE PLANS: The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole. TRIAL REGISTRATION NUMBER: NCT04098315.

Association between SARS-CoV-2 RNAemia, skewed T cell responses, inflammation, and severity in hospitalized COVID-19 people living with HIV.

Severe COVID-19 outcomes have been reported in people living with HIV (PLWH), yet the underlying pathogenetic factors are largely unknown. We therefore aimed to assess SARS-CoV-2 RNAemia and plasma cytokines in PLWH hospitalized for COVID-19 pneumonia, exploring associations with magnitude and functionality of SARS-CoV-2-specific immune responses. Eighteen unvaccinated PLWH (16/18 on cART; median CD4 T cell count 361.5/µL; HIV-RNA<50 cp/mL in 15/18) and 18 age/sex-matched people without HIV were consecutively recruited at a median time of 10 days from symptoms onset. PLWH showed greater SARS-CoV-2 RNAemia, a distinct plasma cytokine profile, and worse respiratory function (lower PaO2/FiO2nadir), all correlating with skewed T cell responses (higher perforin production by cytotoxic T cells as well as fewer and less polyfunctional SARS-CoV-2-specific T cells), despite preserved humoral immunity. In conclusion, these data suggest a link between HIV-related T cell dysfunction and poor control over SARS-CoV-2 replication/dissemination that may in turn influence COVID-19 severity in PLWH.

Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centered approach. Consensus Guidance Using a Delphi Process.

Definitive data on the long-term success of the latest antiretroviral therapy (ART) strategies are still lacking. A panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow ART over time. Panelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Ninety infectious diseases specialists from several Infectious Diseases Centers in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long-term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need for an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality-of-life monitoring during the standard follow up of people living with HIV. The consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.

Influence of efavirenz and 8-hydroxy-efavirenz plasma levels on cognition and central nervous system side effects.

OBJECTIVES: To investigate whether efavirenz (EFV) or 8-hydroxy-EFV (8-OH-EFV) plasma levels are associated with neurocognitive impairment and central nervous system (CNS) side effects. METHODS: We conducted a cross-sectional analysis to explore the potential links between EFV/8-OH-EFV levels and cognitive performance or CNS-related side effects in patients screened within a randomized trial involving a switch from EFV to rilpivirine. The Mann-Whitney test was employed to compare drug levels in patients with or without cognitive impairment, depression, anxiety, sleep disorder or CNS symptoms. Additionally, Spearman's test was used to assess correlations between drug levels and test scores. RESULTS: Among 104 patients, neither EFV nor 8-OH-EFV levels were linked to cognitive impairment, although trends towards higher EFV levels were observed in those with impaired executive function (p = 0.055) and language performances (p = 0.021). On the other hand, elevated 8-OH-EFV levels, but not EFV levels, were associated with more CNS side effects (222 vs. 151 ng/mL, p = 0.027), depressive symptoms (247 vs. 164 ng/mL, p = 0.067) and sleep impairment (247 vs. 164 ng/mL, p = 0.078). Consistently, a trend towards a correlation between EFV levels and lower z-scores in executive function and motor function was observed, while 8-OH-EFV levels, but not EFV levels, were directly correlated with symptom scores. CONCLUSIONS: Higher levels of 8-OH-EFV were associated with CNS side effects, while EFV levels were only marginally associated with cognitive performance, thus suggesting that EFV and its metabolite may act differently in determining detrimental neurological effects.

Neutralizing monoclonal antibodies for the prevention of severe COVID-19: a retrospective study during Omicron BA.1 variant surge.

Among treatment options for Coronavirus disease 2019 (COVID-19), monoclonal antibodies (mAbs) showed to be effective in preventing disease progression, but real-world data during the Omicron variant surge are still lacking. Multicentre retrospective study evaluating the effectiveness of sotrovimab and casirivimab-imdevimab in fragile patients with mild SARS-CoV-2 infection between November 2021 and March 2022. Unfavourable outcome was defined as increased need for oxygen supplementation and/or death. Of 268 study-participants, 12 (4.48%) previously needed supplemental oxygen, while 6 (2.24%) had active solid neoplasia (2.24%); 186 (69%) have previously received SARS-CoV-2 vaccination. Overall, 22 (8%) had unfavourable outcomes (42% versus 6% of patients with and without previous oxygen need and 50% versus 7% of patients with and without active solid neoplasia). Both supplemental oxygen therapy before SARS-CoV-2 infection and solid malignant tumour have shown to be risk factors for treatment failure. Log-rank test did not identify differences between sotrovimab and casirivimab-imdevimab treatment. Despite diffusion of Omicron variant, the rate of unfavourable outcome was higher than expected. The presence of underlying risk factors, including solid cancer and previous oxygen therapy are independently associated with risk of COVID-19 progression, suggesting the need for antiviral treatments not limited to mAbs and implementation of vaccine campaign.

Early diagnosis of candidemia with explainable machine learning on automatically extracted laboratory and microbiological data: results of the AUTO-CAND project.

BACKGROUND: Candidemia is associated with a heavy burden of morbidity and mortality in hospitalized patients. The availability of blood culture results could require up to 48-72 h after blood draw; thus, early treatment decisions are made in the absence of a definite diagnosis. METHODS: In this retrospective study, we assessed the performance of different supervised machine learning algorithms for the early differential diagnosis of candidemia and bacteremia in adult patients on a large dataset automatically extracted within the AUTO-CAND project. RESULTS: Overall, 12,483 episodes of candidemia (1275; 10%) or bacteremia (11,208; 90%) were included in the analysis. A random forest classifier achieved the best diagnostic performance for candidemia, with sensitivity 0.98 and specificity 0.65 on the training set (true skill statistic [TSS] = 0.63) and sensitivity 0.74 and specificity 0.57 on the test set (TSS = 0.31). Then, the random classifier was trained in the subgroup of patients with available serum ß-D-glucan (BDG) and procalcitonin (PCT) values by exploiting the feature ranking learned in the entire dataset. Although no statistically significant differences were observed from the performance measures obtained by employing BDG and PCT alone, the performance measures of the classifier that included the features selected in the entire dataset, plus BDG and PCT, were the highest in most cases. CONCLUSIONS: Random forest classifiers trained on large datasets of automatically extracted data have the potential to improve current diagnostic algorithms for candidemia. However, further development through implementation of automatically extracted clinical features may be necessary to achieve crucial improvements.

Barriers to HCV micro-elimination in a cohort of people living with HIV (PLWH).

To achieve the World Health Organization goal of hepatitis C virus (HCV) eradication, barriers to treatment should be investigated and overcome. The aim of this study was to identify those barriers and describe the strategies adopted to achieve HCV micro-elimination in a cohort of coinfected people living with HIV (PLWH-HCV). Adult PLWH-HCV followed at our hospital with detectable serum HCV-RNA in 2018 were enrolled. After a three-year follow-up, barriers to HCV treatment were investigated and strategies to overcome them were described. Of 492 PLWH-HCV seen in 2018, 29 (5.9%) had detectable serum HCV-RNA. Eight out of 29 (27.6%) were excluded because they were already under treatment, while 2 others were excluded because they moved to other outpatient clinics. Among the remaining 19 study participants, the most common barriers to treatment were poor adherence to therapies and follow-up visits (n=9, 47%), recent HCV diagnosis awaiting proper staging (n=3, 16%) and treatment hesitancy (n=2, 10%). During the following three years, direct-acting antivirals (DAAs) treatment was completed in 11/19 (58%) cases, with achievement of sustained virological response in 100% of cases. For the remaining cases, 2/19 (10.5%) were lost to follow-up, 2/19 (10.5%) died before treatment initiation and 4/19 (21.0%) are still awaiting treatment. Despite 3 years of effort, HCV micro-elimination has not been achieved at our center. We observed that poor adherence and treatment hesitancy were the main barriers to treatment. Strategies addressing these issues need to be implemented.

Pillars of long-term antiretroviral therapy success.

BACKGROUND: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. METHODS: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. RESULTS: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. CONCLUSIONS: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

Real-life safety of Emtricitabine/Tenofovir Alafenamide/Bictegravir.

INTRODUCTION: Integrase strand transfer inhibitors (INSTI) are one of the most prescribed drug classes for the treatment of HIV infection worldwide. Emtricitabine/Tenofovir Alafenamide/ Bictegravir (FTC/TAF/BIC) has been evaluated in randomized clinical trials; few studies have verified tolerability and safety in clinical practice. Our aim was to investigate the metabolic and hepatic safety in a real-life setting of FTC/TAF/BIC. MATERIALS AND METHODS: Consecutive people living with HIV infection (PLWH) enrolled in the SCOLTA project, switching to or initiating their first antiretroviral treatment with FTC/TAF/BIC were included. PLWH with HBV co-infection were excluded. Metabolic and hepatic variables were collected at T0 and T1, were defined as baseline and 6-month follow-up respectively, and their modifications were analysed using the paired t-test and the analysis of variance. RESULTS: Five hundred and thirty-nine PLWH with at least one follow-up visit were included in the analysis. Mean age was 48 years (±12.1), 74% were male, 16.1% were naïve to antiretrovirals (ART). At T1, ART-experienced PLWH showed a significant reduction of total cholesterol (TC) and triglycerides, and a slight increase in blood glucose (BG) and ALT. On the contrary, in ART-naïve PLWH blood lipids significantly increased, although with an unaffected TC/high density lipoprotein (HDL)-c ratio, while alanine aminotransferase (ALT) decreased significantly, mainly in those with altered baseline level. The treatment interruptions were 45 (8.4%) over the whole observation period, 13 (2.4%) due to AEs. The most frequent AEs were related to the central nervous system (6 events of depression, insomnia, headache, agitation) and 3 PLWH discontinued the regimen because of grade 1-2 weight gain. CONCLUSIONS: In ART-experienced PLWH switching to FTC/TAF/BIC a significant improvement of lipid profile occurred but with significant BG and ALT variation without clinical relevance. In ART-naïve PLWH, blood lipids increased even though lipid profile did not worsen, and a trend towards normalization of liver enzymes was suggested. FTC/TAF/BIC is well tolerated in the real life setting.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting.

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (-0.36, p < 0.0001) than in the RPV cohort (-0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (-14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

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.

PRESTIGIO RING: "A 59-year-old HIV-1 positive, highly treatment-experienced woman failing darunavir/ ritonavir plus raltegravir".

Management of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who failed darunavir/ritonavir plus raltegravir at low-viremia levels due mainly to high pill burden and poor adherence. NGS-GRT was performed on HIV-RNA at failure and the results were compared to all past SS-GRT data available (historical genotype). In this case, NGS-GRT did not detect any minority drug-resistant variants. After discussing several therapeutic options, the treatment was changed to dolutegravir 50 mg twice daily plus doravirine 100 mg once a day, based on clinical history, adherence issues, and pill burden, as well as the historical SS-GRT and the latest NGS-GRT results. At six months follow-up visit, the patient had HIV-RNA below 30 copies/ml and CD4+ T cell count increased from 673 cells/ mm3 to 688 cells/ mm3. Close follow-up of this patient is ongoing.

External validation of unsupervised COVID-19 clinical phenotypes and their prognostic impact.

BACKGROUND: Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis. METHODS: Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method. RESULTS: Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81-5.30, p < 0.001) and for phenotype C vs. B (HR 2.20, 95% CI 1.50-3.23, p < 0.001). A non-statistically significant trend towards higher mortality was also observed for phenotype B vs. A (HR 1.41; 95% CI 0.92-2.15, p = 0.115). By means of cluster analysis, three different phenotypes were also identified in our cohort, with an overall similar gradient in terms of prognostic impact to that observed when patients were assigned to FEN-COVID-19 phenotypes. CONCLUSIONS: The prognostic impact of FEN-COVID-19 phenotypes was confirmed in our external cohort, although with less difference in mortality between phenotypes A and B than in the original study.

Hospitalized patients with COVID-19 can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory featuresIn this study, we externally confirmed the prognostic impact of clinical phenotypes previously identified by Gutierrez-Gutierrez and colleagues in a Spanish cohort of hospitalized patients with COVID-19, and the usefulness of their simplified probabilistic model for phenotypes assignmentThis could indirectly support the validity of both phenotype's development and their extrapolation to other hospitals and countries for management decisions during other possible future viral pandemics.

Lipids and transaminase elevations in ARV-experienced PLWH switching to a doravirine-based regimen from rilpivirine or other regimens.

BACKGROUND: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. METHODS: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. RESULTS: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. CONCLUSIONS: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF.