ABSTRACT
BACKGROUND: Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations. METHODS: This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations. RESULTS: A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05). CONCLUSIONS: Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug-drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH.
ABSTRACT
BACKGROUND: Advanced HIV disease (AHD) is increasing, with late presentation accounting for half of newly diagnosed people with HIV (PWH) in Europe. Mortality in late-presenting PWH remains high, and Mycobacterium avium complex (MAC) disease, among other opportunistic infections, presents several diagnostic and treatment challenges that lead, ultimately, to a poor clinical outcome. OBJECTIVES: We aimed to provide guidance on the diagnosis and treatment of disseminated MAC disease (dMACd) in PWH. SOURCES: We performed a review of original articles, meta-analyses, and systematic reviews retrieved from PubMed. CONTENT: We reviewed and discussed the most challenging steps in the management of PWH with AHD and dMACd: the current epidemiology in the era of effective antiretroviral treatment (ART); clinical presentation and interpretation of symptoms in the context of other opportunistic infections and immune reconstitution; diagnosis, sampling, and timing to reach a definitive diagnosis; prophylaxis, treatment options, and indications for discontinuing MAC treatment; future perspectives, and the role of rifamycins in the treatment of dMACd. IMPLICATIONS: Despite the widespread availability of effective ART, dMACd still represents a major cause of morbidity and mortality in PWH with AHD. Residual challenges are mainly related to the difficulties and timing required to reach a definitive diagnosis, and the discussion regarding the role of rifamycins in the treatment of dMACd is still open.
ABSTRACT
The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non-HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)-HPV and low risk (LR)-HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR-HPV 16, reinforcing the urge for a greater vaccination coverage.
Subject(s)
Coinfection , Papillomavirus Infections , Sexually Transmitted Diseases , Humans , Female , Prevalence , Adult , Male , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Middle Aged , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/virology , Young Adult , Coinfection/epidemiology , Coinfection/virology , Adolescent , Anal Canal/virology , Anal Canal/microbiology , Mycoplasma genitalium/isolation & purification , Papillomaviridae/isolation & purification , Papillomaviridae/genetics , Papillomaviridae/classification , Aged , Chlamydia trachomatis/isolation & purification , Gonorrhea/epidemiology , Chlamydia Infections/epidemiology , Chlamydia Infections/microbiology , Trichomonas vaginalis/isolation & purification , Mycoplasma Infections/epidemiology , Neisseria gonorrhoeae/isolation & purificationABSTRACT
BACKGROUND: The diagnosis and management of malaria in non-endemic countries presents a continuing challenge. Plasmodium falciparum, which is capable of rapidly inducing severe and life-threatening multiorgan disease, is the species most frequently diagnosed in Europe and North America. OBJECTIVES: To summarise the more relevant diagnostic findings and clinical features of malaria observed in non-endemic settings and to provide an update of the key management decision points using three illustrative clinical scenarios of uncomplicated and severe malaria. SOURCES: The discussion is based on a relevant literature search spanning the last 20 years. Recommendations are based on available clinical guidelines including those of the WHO, observational studies conducted in non-endemic settings, and, when available, extrapolation from randomised studies from malaria-endemic settings. CONTENT: The following topics are covered: diagnosis, including the use of molecular biology; clinical characteristics; management with a specific focus on complicated (severe) and uncomplicated malaria; and areas of resistance to available antimalarial drugs. IMPLICATIONS: Malaria imported to non-endemic settings, especially P. falciparum malaria, is sometimes initially overlooked and the delayed diagnosis is responsible for every year of preventable deaths. This review aims to raise awareness of malaria outside endemic countries and to provide clinicians with a practical guide for efficient diagnosis and targeted therapy for the different species involved.
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The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three periods characterised by the Italian prevalence of an Omicron variant of concern: (1) January-May 2022 (BA.1-BA.2), (2) June-October 2022 (BA.5), and (3) November 2022-March 2023 (BQ.1-XBB). Inappropriate treatment was defined as pre-hospitalisation exposure to antibiotics and/or steroids in the absence of a documented bacterial infection or the need for steroid treatment of an underlying medical condition. A total of 931 subjects were hospitalised: 394 in period 1, 334 in period 2, and 203 in period 3. Of the 157 patients undergoing inappropriate treatment (16.9%), 142 (15.3%) received antibiotics and 52 (5.6%) steroids. The proportion of inappropriately treated patients significantly decreased over time, from 23.1% in period 1 to 11.7% in period 2 and 13.3% in period 3 (p < 0.001), and there was a parallel decrease in antibiotic (p < 0.001) and steroid treatment (p < 0.013). Only 13 subjects (1.4%) received early pre-hospitalisation treatment for SARS-CoV-2. A significant proportion of hospitalised COVID-19 patients were exposed to inappropriate treatment before hospital admission.
Subject(s)
Anti-Bacterial Agents , Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Hospitalization , SARS-CoV-2 , Steroids , Humans , Male , Female , Retrospective Studies , Middle Aged , COVID-19/epidemiology , Steroids/therapeutic use , Anti-Bacterial Agents/therapeutic use , Aged , SARS-CoV-2/drug effects , Antiviral Agents/therapeutic use , Italy/epidemiology , Adult , Aged, 80 and overABSTRACT
Staphylococcus aureus bacteraemia (SAB) is a life-threatening bloodstream infection. Improved adherence to quality-of-care indicators (QCIs) can significantly enhance patient outcomes. This quasi-experimental study evaluated the impact of a bundle of interventions on QCI adherence in adult patients with SAB. Additionally, a molecular rapid diagnostic test (mRDT) for S. aureus and methicillin resistance was introduced during weekdays. We compared pre-intervention (January-December 2022) and post-intervention (May 2023-April 2024) data on QCI adherence and time to appropriate treatment. A total of 56 and 40 SAB episodes were included in the pre- and post-intervention periods, respectively. Full QCI adherence significantly increased from 28.6% to 67.5% in the post-intervention period (p < 0.001). The mRDT diagnosed SAB in eight cases (26.6%), but the time to achieve appropriate target therapy did not improve in the post-intervention period (54 h (IQR 30-74) vs. 72 h (IQR 51-83), p = 0.131). The thirty-day mortality rate was comparable between the two periods (17.9% vs. 12.5%, p = 0.476). This study demonstrates that a bundle of interventions can substantially improve adherence to SAB management QCIs.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , Drug Therapy, Combination , Immunocompromised Host , SARS-CoV-2 , Humans , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/administration & dosage , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/administration & dosage , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , SARS-CoV-2/drug effects , COVID-19 , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Treatment Outcome , Adenosine/analogs & derivativesABSTRACT
Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals.
Subject(s)
Anti-HIV Agents , HIV Infections , Medication Adherence , Pre-Exposure Prophylaxis , Humans , HIV Infections/prevention & control , Anti-HIV Agents/therapeutic useSubject(s)
Anti-HIV Agents , Drug Resistance, Viral , HIV Infections , Viral Load , Humans , HIV Infections/drug therapy , HIV Infections/virology , Retrospective Studies , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacology , Male , Female , Viral Load/drug effects , Middle Aged , Treatment Failure , Adult , Registries , HIV-1/drug effects , HIV-1/geneticsABSTRACT
Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.
Subject(s)
COVID-19 , Hemorrhage , Hospitalization , Humans , COVID-19/complications , Retrospective Studies , Aged , Male , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Italy/epidemiology , Aged, 80 and over , Middle Aged , Hospitalization/statistics & numerical data , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , Risk Factors , Prevalence , SARS-CoV-2 , Age Factors , Proportional Hazards ModelsSubject(s)
Anti-HIV Agents , HIV Infections , Humans , HIV Infections/drug therapy , Italy , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/economics , Male , Female , Middle Aged , Adult , Outpatients , Cost Savings , Cohort Studies , Tenofovir/therapeutic useABSTRACT
OBJECTIVE: Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia. CASE REPORT: A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium. CONCLUSIONS: We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.
Subject(s)
Drug Interactions , Drug Monitoring , HIV Infections , Heterocyclic Compounds, 3-Ring , Oxazines , Piperazines , Pyridones , Valproic Acid , Humans , Male , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Heterocyclic Compounds, 3-Ring/therapeutic use , Pyridones/therapeutic use , Pyridones/pharmacokinetics , Piperazines/therapeutic use , Middle Aged , Valproic Acid/therapeutic use , HIV Infections/drug therapy , Drug Monitoring/methods , HIV Integrase Inhibitors/therapeutic use , HIV Integrase Inhibitors/pharmacokinetics , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacokineticsABSTRACT
BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.
Subject(s)
Carbamazepine , Darunavir , Drug Interactions , HIV Infections , Humans , Darunavir/therapeutic use , Darunavir/pharmacokinetics , Male , Middle Aged , Carbamazepine/therapeutic use , Carbamazepine/pharmacokinetics , HIV Infections/drug therapy , Trigeminal Neuralgia/drug therapy , Ritonavir/therapeutic use , Ritonavir/administration & dosage , Anticonvulsants/pharmacokinetics , Anticonvulsants/therapeutic use , Anticonvulsants/administration & dosage , Pyridones/pharmacokinetics , Pyridones/therapeutic use , Pyridones/blood , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , Piperazines/therapeutic use , Piperazines/pharmacokinetics , Oxazines/therapeutic use , Oxazines/pharmacokinetics , Dose-Response Relationship, Drug , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/administration & dosage , Drug Monitoring/methodsSubject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Humans , Male , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/immunology , Female , VaccinationABSTRACT
In October, 2022, WHO published the first fungal priority pathogen list, which categorised 19 fungal entities into three priority groups (critical, high, and medium), for prioritisation of research efforts. The final ranking was determined via multiple criteria decision analysis, considering both research and development needs and perceived public health importance. In this Personal View, we discuss the positioning of the fungal pathogens, namely, Mucorales, Candida spp, Histoplasma spp, Coccidioides and Paracoccidioides spp, Fusarium spp, eumycetoma causative agents, Talaromyces marneffei, and Pneumocystis jirovecii, while expressing concerns about potential disparities between the WHO fungal priority pathogen list ranking and the actual disease burden associated with these pathogens. Finally, we propose a revised prioritisation list that also considers the regional disparities in the burden of fungal diseases.