Toxoplasmosis mimicking CMV chorioretinitis in newly diagnosed PLWH: a case report.

Background: cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/µL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed. Results: the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, Toxoplasma gondii serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for Toxoplasma gondii, while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of Toxoplasma gondii uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement. Conclusions: despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).

Inflammation markers in virologically suppressed HIV-Infected patients after switching to dolutegravir plus lamivudine vs continuing triple therapy: 48-week results in real-life setting.

Objectives: To evaluate the impact of a treatment switch to dolutegravir plus lamivudine on the soluble inflammatory biomarkers of HIV-infected patients treated in a real-life setting.Materials and methods: This was a longitudinal study that enrolled virologically-suppressed patients on stable 3-drug ART who switched at baseline to dolutegravir + lamivudine (2DR-group), based on the clinician's decision, or maintained triple therapy (3DR-group). Subjects in the 3DR-group were matched with those in the 2DR-group for age, gender and type of anchor drug. Plasma levels of interleukin-6 (IL-6), I-FABP, D-dimer and C-reactive protein (CRP) were quantified by a microfluidic ultrasensitive ELISA assay at baseline and at 48 weeks.Results: Overall 208 subjects were enrolled: 101 in the 2DR-group and 107 in the 3DR-group. At baseline, biomarker levels were comparable between groups. The differences in mean log10 change from baseline to 48 weeks between groups (2DR versus 3DR) were: IL-6 (pg/L) -0.051(95% CI -0.115/0.009) versus 0.004 (95% CI -0.046/0.054) (p = 0.159); I-FABP (pg/mL), -0.088 (95% CI -0.14/-0.041) versus 0.033 (95%CI -0.007/0.072) (p < 0.001); D-dimer (pg/mL), -0.011(95% CI-0.055/0.033) versus -0.021 (95% CI -0.071/0.030) (p = 0.780) and CRP (pg/mL), -0.028 (95%CI -0.118/0.063) versus 0.118 (95% CI 0.024/0.211) (p = 0.028).Conclusions: At 1 year, switching to a dolutegravir plus lamivudine dual regimen in this setting showed a favorable trend for two biomarkers analyzed, i.e., I-FABP and CRP, as compared to continuing a triple therapy. These results add important new data in support of the safety of this approach in terms of its effect on the inflammatory milieu.

Implementing a Personalized Antimicrobial Stewardship Program for Women with Gynecological Cancers and Healthcare-Associated Infections.

Healthcare-associated infections (HCAIs) represent a major cause of morbidity and mortality in gynecologic cancer patients, requiring personalized cures. A retrospective study on gynecologic patients with HCAIs, managed through an antimicrobial stewardship program, was performed, focusing on rates of clinical cure, breakthrough/relapse of infections, death, and time of hospital stay (THS). In total, 27 patients (median 60 years, mainly suffering from ovarian, cervical, and uterine cancer) were evaluated by a specialist in infectious diseases and were mainly diagnosed with complicated urinary tract (cUTIs, 12 cases, 44.4%) and bloodstream infections (BSIs, 9 cases, 33.3%). A total of 15 cases (11 cUTIs, 73.3%) were managed with no need for hospitalization and received a median of 11 days of outpatient parenteral antimicrobial therapy (OPAT). In the remaining 12 cases (BSIs in 8 cases, 66.7%), the median THS was 11 days, with 15 days median overall duration of antimicrobial therapy (median 5-day reduction in THS). The management of patients also included source control and wound care. All patients reached clinical cure, with no case of breakthrough infection, one case of relapse, and one death within 30 days (not attributable to the infection). HCAIs in patients with gynecologic tumors can be managed through a patient-centered, multidisciplinary antimicrobial stewardship program.

Has COVID-19 changed the approach to HIV diagnosis?: A multicentric Italian experience.

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Risk of Tumor Onset in HIV+ Patients on Two-Drug Regimens: A Cohort Study in an Italian Hospital.

Currently approved 2-drug therapies are as effective as 3-drug regimens but could potentially lead to increased cancer risk due to less efficient immune recovery. We conducted a longitudinal cohort study in a tertiary Italian hospital to investigate HIV+ patients starting a triple therapy (TT) (2 NRTIs +3rd agent) or a dual therapy (DT) (3TC/FTC+boosted-PI, boosted-DRV+RAL, and 3TC/FTC or RPV+DTG) regimen between 2009 and 2018. The effect of DT (vs. TT) on tumor onset was evaluated by the multivariable Cox regression and the marginal structural Cox model, after estimating the inverse probability of treatment weights (IPTW). One thousand one hundred and seven patients who had a median follow-up of 4.2 person-years (py) were evaluated; 69.2% were males, with a median age of 43 years. Overall 2,513 treatments were started during the study period (479 DT, 2,034 TT). Eight tumors occurred over 965 py with DT and 35 over 3,817 py during TT (p = .797). In the Cox regression, DT did not predict an increased risk of tumor compared with TT (HR 1.14; p = .757) after adjusting for potential confounders. A marginal structural model using IPTW (HR 0.68; p = .328) and stabilized IPTW (HR 0.69; p = .361) confirmed this result. Preliminary findings from our cohort do not suggest an increased risk of tumors with DT compared to TT.

Comparison of HIV-DNA decay in naive patients starting dolutegravir plus lamivudine or dolutegravir-based triple therapy.

Not available.

Impact of Antiretroviral Therapy on the Risk of Recurrence in HIV-1 Infected Patients with Kaposi Sarcoma: A Multicenter Cohort Experience.

Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the impact of new drugs, drug classes or paradigms was never investigated nor proven better than previous therapeutic regimes. In order to do this, we retrospectively collected data regarding HIV-infected patients with a diagnosis of KS last seen in six Italian centers after 1 January 2013. A total of 104 KS cases in 99 patients was analyzed for 945.34 patient-year follow-up (PYFU). Twenty-six patients had visceral localizations. Thirty-three patients were treated with chemotherapy, four with electrochemotherapy, and 12 with α-interferon (α-IFN). At censor, 22% received a bPI-based, 14% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, and 28% an integrase inhibitor (INI)-based standard cART, 24% a less drug regimen and 12% a mega-cART. Twelve recurrence episodes were observed in seven patients for an incidence of 1.27 per 100 PYFU. Two patients with no evidence of recurrence episodes died for other reasons. In our experience, KS recurrence episodes were infrequent. Despite the increasing use of new antiretroviral drug classes and new treatment paradigms, no excess of recurrence episodes was observed in patients receiving such cART regimens.

Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report.

BACKGROUND: Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen. CASE PRESENTATION: We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed. DISCUSSION: Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.

Systemic inflammation markers after simplification to atazanavir/ritonavir plus lamivudine in virologically suppressed HIV-1-infected patients: ATLAS-M substudy.

Background: Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives: To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods: In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results: A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, -0.030 versus -0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, -0.016 versus +0.019 log10 pg/mL; and D-dimer, -0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions: Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation.