Low plasmatic concentration of intensified antiretroviral therapy in a pregnant woman: a case report

Identifying the most appropriate antiretroviral regimen for pregnant women with Human Immunodeficiency Virus (HIV-1) infection can be challenging, mainly due to pregnancy-related physiological alterations which can significantly reduce maternal drug plasma concentration. We would like to report our experience as it consists of an unusual case of low plasmatic concentration of antiretroviral drugs despite regimen intensification in a HIV-positive pregnant woman. It also underlines the need for accurate monitoring and treatment adjustment in pregnant women with Human Immunodeficiency Virus (HIV)

HIV-1-Associated Neurocognitive Disorders: Is HLA-C Binding Stability to β2-Microglobulin a Missing Piece of the Pathogenetic Puzzle?

AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND) are complications of HIV-1 infection. Viral infections are risk factors for the development of neurodegenerative disorders. Aging is associated with low-grade inflammation in the brain, i.e., the inflammaging. The molecular mechanisms linking immunosenescence, inflammaging and the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease, are largely unknown. ADC and HAND share some pathological features with AD and may offer some hints on the relationship between viral infections, neuroinflammation, and neurodegeneration. β2-microglobulin (β2m) is an important pro-aging factor that interferes with neurogenesis and worsens cognitive functions. Several studies published in the 80–90s reported high levels of β2m in the cerebrospinal fluid of patients with ADC. High levels of β2m have also been detected in AD. Inflammatory diseases in elderly people are associated with polymorphisms of the MHC-I locus encoding HLA molecules that, by associating with β2m, contribute to cellular immunity. We recently reported that HLA-C, no longer associated with β2m, is incorporated into HIV-1 virions, determining an increase in viral infectivity. We also documented the presence of HLA-C variants more or less stably linked to β2m. These observations led us to hypothesize that some variants of HLA-C, in the presence of viral infections, could determine a greater release and accumulation of β2m, which in turn, may be involved in triggering and/or sustaining neuroinflammation. ADC is the most severe form of HAND. To explore the role of HLA-C in ADC pathogenesis, we analyzed the frequency of HLA-C variants with unstable binding to β2m in a group of patients with ADC. We found a higher frequency of unstable HLA-C alleles in ADC patients, and none of them was harboring stable HLA-C alleles in homozygosis. Our data suggest that the role of HLA-C variants in ADC/HAND pathogenesis deserves further studies. If confirmed in a larger number of samples, this finding may have practical implication for a personalized medicine approach and for developing new therapies to prevent HAND. The exploration of HLA-C variants as risk factors for AD and other neurodegenerative disorders may be a promising field of study

Dolutegravir monotherapy and body weight gain in antiretroviral na\uefve patients

no abstract available; Correspondenc

Efficacy and safety of abacavir/lamivudine with raltegravir in treatment-experienced and treatment-na\uefve patients with HIV-1 infection: an observational, retrospective, multi-centre study

Raltegravir (RAL) is an HIV-1 integrase strand transfer inhibitor that is well established as a component of highly active antiretroviral therapy regimens for the treatment of adults living with human immunodeficiency virus (HIV), due to its high virological efficacy and good tolerability profile. To date, limited data are available on the use of RAL with abacavir/lamivudine (ABC/3TC). We investigated retrospectively 62 HIV-1 infected patients managed by three Italian Infectious Diseases Outpatient Departments, including 57 treatment-experienced patients and 5 treatment-na\uefve patients, treated with ABC/3TC plus RAL. In all five na\uefve patients (100%), virological suppression was achieved and maintained , while 55 experienced patients (96.5%) maintained viral suppression at the most recent review. In the treatment-experienced patients, we observed a significant decrease in triglyceride levels (p\u2009<\u20090.01), while liver transaminases, renal function and cholesterol levels remained substantially stable. In the 34 treatment-experienced patients who switched from a protease inhibitor (PI)-based regimen, we observed a significant improvement of total cholesterol (p=0.03) and triglyceride (p\u2009<\u20090.01) levels. No significant alterations were found on renal and liver function and serum lipid profile of treatment-na\uefve patients. Despite the small number of participants, results support the efficacy and safety of ABC/3TC plus RAL, either in treatment-na\uefve or treatment-experienced patients

Increase in visceral adipose tissue in a woman living with HIV after introduction of integrase strand transfer inhibitor

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral drugs with high virologic efficacy and excellent tolerability. Recent evidence showed a possible link of dolutegravir-based regimens with weight gain, and a relationship between raltegravir use and changes in adipose tissue density and metabolic abnormalities, with an increased cardiovascular risk, has been suggested. We describe a case where dolutegravir monotherapy led to a decrease in adipose tissue density

Methodological quality of studies evaluating the burden of drug-resistant infections in humans due to the WHO Global Antimicrobial Resistance Surveillance system target bacteria

The health impact of antimicrobial resistance (AMR) has not been included in the Global Burden Disease (GBD) report, as reliable data has been lacking. AMR burden estimates have been derived from models combining incidence and/or prevalence data from national and/or international surveillance systems and mortality estimates from clinical studies. Depending on utilized empirical data, statistical methodology and applied endpoints, the validity and reliability of results can substantially differ

Short-cycle therapy in {HIV}-infected adults: rilpivirine combination 4 days on/3 days off therapy

Background Short-cycle therapy (SCT) is the administration of ART for 4 or 5 consecutive days a week, followed by 3 or 2 days off therapy. Its benefits include improving patient satisfaction and reducing ART toxicity and costs. Methods In this observational study we included HIV-infected adults with a three-drug ART containing rilpivirine, a history of long-term virological suppression and no evidence of resistance to previous drug regimens. Patients switched to a SCT of 4 days on/3 days off and were followed for 48 weeks with regular check-ups. The primary outcome was virological suppression; secondary outcomes were changes in CD4+ cells and rilpivirine plasma concentration, the occurrence of adverse events and resistance in the case of failure, and patient satisfaction. Results At week 48 no virological failure was observed, with a virological suppression rate of 30/30 (100%). Three patients switched back to continuous therapy for other reasons, with an overall success rate of SCT of 30/33 (90.9%, 95% CI = 81.24% to 100%). The CD4+ mean value increased by +64 cells/mm(3) (95% CI = -59 to +187 cells/mm(3); P = 0.052). No adverse events were observed and the mean total score in the satisfaction questionnaire was 57.7/60 (96.22%). Rilpivirine plasma concentration was below the efficacy threshold in 71.3% of the samples, suggesting that the patients' characteristics, more than the drug's pharmacokinetics, played a role in maintaining virological suppression. Conclusions SCT with rilpivirine-containing regimens could be an effective alternative to continuous therapy in selected HIV-infected patients with previous long-term virological suppression

Independent risk factors for mortality in critically ill patients with candidemia on Italian Internal Medicine Wards

Candida is an increasing cause of bloodstream infection and is associated with significant morbidity and mortality. The aim of our study is to analyze risk factors for short-term mortality in patients with bloodstream Candida spp. infections admitted to Internal Medicine Wards (IMWs). This was a retrospective case-control study between January 2012 and December 2014 from four University Hospitals in Italy, where patients with candidemia dying within 30 days from diagnosis were matched to control cases with candidemia who survived in the same period of time. Two-hundred and fifty cases of candidemia were registered during the 36&nbsp;months of enrollment. Among these, 112 patients died (45%) within 30 days from the first blood culture's positivity for Candida spp. At multivariate analysis, septic shock [odds ratio (95% CI)&nbsp;=&nbsp;2.919 (1.62-5.35), p&nbsp;&lt;&nbsp;0.001] and concomitant chronic kidney failure [odds ratio (95% CI)&nbsp;=&nbsp;2.296 (1.07-5.12), p = 0.036] were independent predictors of mortality. Low-dose chronic steroid therapy was protective [odds ratio (95% CI)&nbsp;=&nbsp;0.461 (0.25-0.83), p = 0.011)