Managing low-level HIV viraemia in antiretroviral therapy: a systematic review and meta-analysis

objective: HIV-1 management has advanced significantly with antiretroviral therapy (ART), yet challenges persist, including low-level HIV-1 viraemia (LLV). LLV presents a complex scenario, with varied definitions in the literature, reflecting uncertainties in its clinical interpretation. questions arise regarding the underlying mechanisms of LLV, whether it signifies ongoing viral replication or stems from other factors. this study aimed to systematically review strategies for LLV management, providing insights into optimal clinical approaches. methods: MEDLINE, EMBASE, cochrane library, web of science and canadian agency for drugs and technologies in health were searched for relevant literature on LLV management. We included studies published between 2004 and 2024, assessing interventions such as ART modification, genotypic resistance testing, adherence assessment, performing therapeutic drug monitoring, testing for chronic coinfections and assessing the viral reservoir via HIV DNA quantification. meta-analyses were conducted where feasible. results: the systematic review identified 48 eligible records. findings indicated limited evidence supporting the effectiveness of ART regimen modification in achieving virological suppression among individuals with LLV. however, studies assessing genotypic resistance testing revealed a significant association between resistance-associated mutations and virological suppression during LLV. adherence to ART emerged as a critical determinant of treatment efficacy, with interventions showing promise in achieving viral suppression. the clinical utility of therapeutic drug monitoring in managing LLV remained inconclusive. gaps in the literature were identified regarding follow-up scheduling, managing concurrent chronic infections and assessing inflammatory markers in LLV management. conclusions: While ART modification may not consistently achieve virological suppression, genotypic resistance testing may offer insights into treatment outcomes. adherence to ART emerged as a crucial factor, necessitating tailored interventions. however, further research is needed to elucidate the clinical utility of therapeutic drug monitoring and other management strategies. the study highlights the importance of ongoing research to refine therapeutic approaches and improve patient outcomes in LLV management. prospero registration number: CRD42024511492

Resistance to Ceftazidime/Avibactam in Klebsiella pneumoniae KPC-Producing Isolates: A Real-Life Observational Study

Background: Ceftazidime/avibactam (CAZ-AVI) resistance amongst Enterobacterales is worryingly increasing worldwide. Objectives: The aim of this study was to collect and describe real-life data on CAZ-AVI-resistant Klebsiella pneumoniae (KP) isolates in our University Hospital, with the ultimate goal of evaluating possible risk factors related to the acquisition of resistance. Methods: This is a retrospective observational study, including unique Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI (CAZ-AVI-R) and producing only KPC, collected from July 2019 to August 2021 at Policlinico Tor Vergata, Rome, Italy. The pathogen's list was obtained from the microbiology laboratory; clinical charts of the corresponding patients were reviewed to collect demographic and clinical data. Subjects treated as outpatients or hospitalized for <48 h were excluded. Patients were then divided into two groups: S group, if they had a prior isolate of CAZ-AVI-susceptible KP-KPC, and R group, if the first documented isolate of KP-KPC was resistant to CAZ-AVI. Results: Forty-six unique isolates corresponding to 46 patients were included in the study. The majority of patients (60.9%) were hospitalized in an intensive care unit, 32.6% in internal medicine wards and 6.5% in surgical wards. A total of 15 (32.6%) isolates were collected from rectal swabs, representing a colonization. Amongst clinically relevant infections, pneumonia and urinary tract infections were the most commonly found (5/46, 10.9% each). Half of the patients received CAZ-AVI prior to isolation of the KP-KPC CAZ-AVI-R (23/46). This percentage was significantly higher in patients in the S group compared to patients in the R group (69.3% S group vs. 25% R group, p = 0.003). No differences between the two groups were documented in the use of renal replacement therapy or in the infection site. The clinically relevant CAZ-AVI-R KP infections (22/46, 47.8%) were all treated with a combination therapy, 65% including colistin and 55% including CAZ-AVI, with an overall clinical success of 38.1%. Conclusions: Prior use of CAZ-AVI was associated with the emergence of drug resistance

Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort

: The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35-14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly 54% during the entire study follow-up after switching to 2DR-3TC

How Lung Volume Recruitment Maneuvers Enhance Respiratory Function in Multiple Sclerosis Patients: A Quasi-Randomized Pilot Study

Background and Objectives: In patients with multiple sclerosis (MS), a decrease in muscle strength can lead to limitations in pulmonary functions, potentially causing respiratory complications. To address these challenges, the lung volume recruitment (LVR) maneuver has emerged as a potential intervention. This study sought to evaluate the impact of a four-week LVR protocol on respiratory function in secondary progressive MS patients. Materials and Methods: In a quasi-randomized pre/post-controlled trial, 24 patients with secondary progressive MS were recruited. Participants aged 20–70 years with an EDSS score of 2 to 9 were alternately allocated to intervention (n = 12) or control groups (n = 12). The intervention group underwent a 4-week respiratory rehabilitation training focused on LVR, using a standardized cough machine treatment protocol twice daily. The control group received no respiratory intervention. Outcomes measured included forced vital capacity (FVC), maximal insufflation capacity (MIC), and peak cough flow (PCF), using turbine spirometry and other associated equipment. All measurements were taken at baseline (T0) and after 4 weeks (T1) by a blinded assessor. Results: For the intervention group, the mean difference pre/post-treatment in MIC (mL) was 0.45 (SD 1.13) (p = 0.02), and in MIC (%), it was 0.13 (SD 0.24) (p = 0.03). Compared to the control group (n = 10), the between-group mean difference for MIC (mL) was 0.54 (p = 0.02), and for MIC (%), it was 0.15 (p = 0.02). Conclusions: The short-term daily LVR protocol notably improved passive lung capacity, despite minimal changes in active lung capacity or cough force. The LVR maneuver offers promise for enhancing respiratory function, especially passive lung capacity, in secondary progressive MS patients. Further research should explore optimal treatment durations and frequencies for more extensive respiratory gains

Remdesivir Influence on SARS-CoV-2 RNA Viral Load Kinetics in Nasopharyngeal Swab Specimens of COVID-19 Hospitalized Patients: A Real-Life Experience

There are still conflicting data on the virological effects of the SARS-CoV-2 direct antivirals used in clinical practice, in spite of the documented clinical efficacy. The aim of this monocentric retrospective study was to compare virologic and laboratory data of patients admitted due to SARS-CoV-2 infection from March to December 2020 treated with either remdesivir (R), a protease inhibitor (lopinavir or darunavir/ritonavir (PI)) or no direct antiviral drugs (NT). Viral load variation was indirectly assessed through PCR cycle threshold (Ct) values on the nasopharyngeal swab, analyzing the results from swabs obtained at ward admission and 7 (±2) days later. Overall, 253 patients were included: patients in the R group were significantly older, more frequently males with a significantly higher percentage of severe COVID-19, requiring more often intensive care admission, compared to the other groups. Ct variation over time did not differ amongst the three treatment groups and did not seem to be influenced by corticosteroid use, even after normalization of the treatment groups for disease severity. Non-survivors had lower Ct on admission and showed a significantly slower viral clearance compared to survivors. CD4 T-lymphocytes absolute count assessed at ward admission correlated with a reduced Ct variation over time. In conclusion, viral clearance appears to be slower in COVID-19 non-survivors, while it seems not to be influenced by the antiviral treatment received

Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplant Recipients: A Retrospective Italian Cohort Study in Tor Vergata University Hospital, Rome

The results of tuberculosis (TB) screening and reactivation in a cohort of 323 adult patients undergoing haematopoietic stem cell transplantation (HSCT) from 2015 to 2019 at the University Hospital of Tor Vergata, Rome, Italy, were reported. A total of 260 patients, 59 (18.3%) autologous and 264 (81.7%) allogeneic transplants, underwent Interferon Release (IFN)-γ (IGRA) test screening: 228 (87.7%) were negative, 11 (4.2%) indeterminate and 21 (8.1%) positive. Most of the IGRA-positive patients were of Italian origin (95.2%) and significantly older than the IGRA-negative (p < 0.001); 22 (8.5%) patients underwent a second IGRA during the first year after transplantation, and 1 tested positive for IGRA. Significantly lower monocyte (p = 0.044) and lymphocyte counts (p = 0.009) were detected in IGRA negative and IGRA indeterminate patients, respectively. All latent TB patients underwent isoniazid prophylaxis, and none of them progressed to active TB over a median follow-up period of 63.4 months. A significant decline in TB screening practices was shown from 2015 to 2019, and approximately 19% of patients were not screened. In conclusion, 8.1% of our HSCT population had LTBI, all received INH treatment, and no reactivation of TB was observed during the follow-up period. In addition, 19% escaped screening and 8% of these came from countries with a medium TB burden, therefore at higher risk of possible development of TB

Tuberculosis-Related Hospitalizations in a Low-Incidence Country: A Retrospective Analysis in Two Italian Infectious Diseases Wards

In recent years, a decrease in the incidence of tuberculosis (TB) has been recorded worldwide. However, an increase in TB cases has been reported in foreign people living in low-incidence countries, with an increase in extrapulmonary TB (EPTB) in the western region of the world. In the present work, a retrospective study was conducted in two Italian infectious diseases wards to evaluate the clinical characteristics of TB admission in the time period 2013–2017. A significant increase in TB was shown in the study period: 166 (71% males) patients with TB were enrolled, with ~70% coming from outside Italy (30% from Africa, 25% from Europe, and 13% from Asia and South America). Compared to foreign people, Italians were significantly older (71.5 (interquartile range, IQR: 44.5–80.0) vs. 30 (IQR: 24–40) years; p < 0.0001) more immunocompromised (48% vs. 17%; p < 0.0001), and affected by comorbidities (44% vs. 14%; p < 0.0001). EPTB represented 37% of all forms of the disease, and it was more incident in subjects coming from Africa than in those coming from Europe (39.3% vs. 20%, respectively). In logistic regression analysis, being European was protective (odd ratio, OR (95% CI): 0.2 (0.1–0.6); p = 0.004) against the development of EPTB forms. In conclusion, an increase in the rate of TB diagnosis was documented in two Italian reference centers in the period 2013–2017, with 39% of EPTB diagnosed in patients from outside Europe

Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study

: Neuropsychiatric symptoms have been reported in patients receiving dolutegravir, a known inhibitor of the renal and neuronal-expressed organic anion transporter 2 (encoded by SLC22A2 gene). The effect of the genetic variant SLC22A2 808C>A on dolutegravir discontinuation was assessed and analyzed by real-time PCR. We enrolled 627 participants: CA/AA carriers showed a higher prevalence of pre-existing psychiatric comorbidities and use of antidepressants. After 27.9 months, 108 participants discontinued dolutegravir, 64 for neuropsychiatric symptoms. Patients with pre-existing psychiatric comorbidities were at higher risk of dolutegravir discontinuation, while patients carrying the SLC22A2 CA/AA genotype were not. Combining the two variables, an opposite effect of SLC22A2 variants according to pre-existing psychiatric disorders was observed. Using multivariate Cox models, the combined variable pre-existing psychiatric comorbidities/SLC22A2 variants and the use of non-tenofovir alafenamide containing antiretroviral regimens were predictors of dolutegravir discontinuation for neuropsychiatric symptoms. Within 30 days, the majority of participants had a complete resolution of symptoms (61.8%), while 32.7% and 5.5% had partial or no change after dolutegravir discontinuation, respectively. Discontinuation of dolutegravir for neuropsychiatric symptoms was not uncommon and more frequent in participants with pre-existing psychiatric disorders. We described an interaction between SLC22A2 genetic variant and psychiatric comorbidities. In 38.2% of patients, a complete neuropsychiatric symptoms resolution was not observed after dolutegravir discontinuation suggesting the involvement of additional factors