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We describe the outcome of a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG/IgM rapid test, and discuss the potential suitability of antibody testing. Retrospective single cohort study on patients with suspected Coronavirus Disease 2019 (COVID-19) and asymptomatic Healthcare Workers, enrolled from March to April 2020. Subjects had quantitative PCR (qPCR) test for detection of SARS-CoV-2 via nasal swab and serological testing using the COVID-19 IgG/ IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay. Some subjects underwent chemiluminescence immunoassay (CLIA) after rapid test. The aim of the study was to analyse the proportion of those who developed a positive IgM/IgG response for SARS-CoV-2. The correspondence between the results from rapid testing and CLIA, when available, was evaluated. 97 subjects underwent qPCR for SARS-CoV-2 through nasal swab, which resulted positive in 40/43 (93.0%) of symptomatic patients, 2/40 (5%) of asymptomatic HCW, in no subjects with suspected COVID- 19 (clinical and radiological findings) then excluded by repeated nasal swabs and alternative diagnosis (COVID-19-negative patients, CNPs), and in 6/6 (100%) of patients with confirmed diagnosis and negative follow-up nasal swabs (COVID-19-recovered patients, CRPs). IgM resulted positive in 8/43 (18.6%) of symptomatic patients and in 1/6 (16.7%) of CRPs. IgG resulted positive in 36/43 (83.7%) of symptomatic patients, 2/40 (5%) of HCW, and in 1/8 (12.5%) and 6/6 (100%) of CNPs and CRPs, respectively. A comparison between an IgG/IgM Rapid Test and a following CLIA test showed consistency in negative results in 25/28 of HCW and 8/8 of CNPs tested. Our preliminary data support the role of IgG/IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay as a point-of-care test that may complement molecular tests in the screening of SARS-CoV-2 carriers. The test may gain particular relevance in shortening the time needed to refer patients to a COVID or non-COVID Hospital area and to achieve diagnosis in patients with persistently negative nasal swabs.

Objectives The aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19). Methods This was a cohort study of patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine–Gray models to assess factors associated with risk of secondary infections. Results Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4–21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 109/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11–3.35), baseline PaO2/FiO2 (per 100 points lower: sdHRs 1.56, 95%CI 1.21–2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04–6.05). Conclusions Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections.

Objectives Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily treatment-experienced patients with limited therapeutic options. We evaluated the genotypic and phenotypic susceptibility to temsavir in a panel of samples collected from patients harbouring MDR strains enrolled in the Italian PRESTIGIO Registry. Methods Plasma samples from 24 patients were used for HIV-1 gp120 sequencing, while viral tropism and susceptibility to temsavir were assessed through a homemade phenotypic assay with pseudotyped viruses expressing patient-derived Env protein. Results Of the 24 patients enrolled, 18 (75%) were male, median (IQR) age was 55 years (52–61), time since HIV-1 diagnosis was 27 years (24–30), time on ART was 26 years (23–27) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and/or enfuvirtide) had occurred in 19 (79%) patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23/24 samples and viral tropism was CXCR4-tropic, CCR5-tropic and dual/mixed-tropic in six, nine and eight cases, respectively. Phenotypic susceptibility to temsavir was comparable to the reference WT viruses NL4-3 and AD8 in all samples, irrespective of RAMs. Viral tropism and exposure to entry inhibitors did not impact temsavir susceptibility. Conclusions These data support the use of fostemsavir as a valuable therapy option in patients harbouring MDR virus. The role of laboratory testing in optimal screening of patients eligible for fostemsavir treatment remains to be investigated.

Vincenzo Spagnuolo,1,2 Laura Galli,2 Andrea Poli,2 Alba Bigoloni,2 Luca Fumagalli,2 Nicola Gianotti,2 Silvia Nozza,2 Davide Ferrari,3 Massimo Locatelli,3 Adriano Lazzarin,2 Antonella Castagna1,2 1Vita-Salute San Raffaele University, Faculty of Medicine and Surgery, Milan, Italy; 2Clinic of Infectious Diseases, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; 3Laboratory Medicine Service, IRCCS San Raffaele Hospital, Milan, Italy IntroductionThe increased exposure of dolutegravir (DTG) when given with atazanavir/ritonavir(ATV/r), as well as the acceptable safety profile, may suggest the use of this combinationas a two-drug regimen both in virologically suppressed and treatment-failingsubjects.1–5 This nucleoside reverse transcriptase inhibitors (NRTIs)-sparing regimen, characterizedby a high genetic barrier, may represent an option in patients who have failedprevious regimens and developed pharmacoresistance mutations to NRTIs and nonnucleosidereverse transcriptase inhibitors (NNRTIs). However, no data on DTG plus boosted ATV in patients with virological failureare currently available. Therefore, the aim of the DOLATAV study was to investigate the efficacy, safety,and pharmacokinetics of ATV/r 300/100 mg once-daily plus DTG 50 mg once-daily &nbsp

Background The pilot Phase IIb VIKING study suggested that dolutegravir (DTG), an HIV integrase inhibitor (INI), is efficacious in INI-resistant patients at the 50 mg twice-daily dose. However, DTG response was most reduced in subjects carrying resistance-associated mutations at position G140 and Q148. These mutations can cause a 10–20-fold reduced susceptibility to DTG as well as a 96% lower odds of achieving HIV-1 RNA Methods Five multi-experienced patients harbouring the mutation complex G140-Q148, resistant to at least three drug classes, and previously exposed to DTG 50 mg twice daily, were treated with an increased dose of DTG (100 mg twice daily) in association with an optimized background regimen (OBR) based on their individual viral genotyping assays. The blood concentration of DTG was measured in order to determine whether a solubility issue is related with this high dosage. Results Four out of five patients attained an HIV-1 RNA Conclusions For the first time 100 mg twice daily of DTG was administered to five multi-experienced patients harbouring the mutation complex G140-Q148. Although a small number of patients were tested, the results show a potential for a high-dose regimen of DTG as a rescue therapy in patients harbouring integrase strand transfer inhibitor resistant viruses.

ObjectivesDespite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir.Patients and methodsThis was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA 500 cells/mm3, HIV-DNA 50 copies/mL). Results are reported as median (IQR).ResultsNine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47–6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14–56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA ConclusionsDespite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.

OBJECTIVE: To investigate the association between total, direct, and indirect bilirubin and the presence of carotid lesions in a large sample of HIV-1-infected patients on virological suppression. DESIGN: Retrospective study on adult HIV-1-infected patients, with a carotid ultrasound (CUS) examination performed between January 2008 and August 2016, with HIV-RNA

Introduction A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. Methods Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients’ follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters. Results and discussion In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (

Maraviroc (MVC) is licensed in clinical practice for patients with R5 virus and virological failure; however, in anecdotal reports, dual/mixed viruses were also inhibited. We retrospectively evaluated the evolution of HIV-1 coreceptor tropism in plasma and peripheral blood mononuclear cells (PBMCs) of an infected adolescent with a CCR5/CXCR4 Trofile profile who experienced an important but temporary immunological and virological response during a 16-month period of MVC-based therapy. Coreceptor usage of biological viral clones isolated from PBMCs was investigated in U87.CD4 cells expressing wild-type or chimeric CCR5 and CXCR4. Plasma and PBMC-derived viral clones were sequenced to predict coreceptor tropism using the geno2pheno algorithm from the V3 envelope sequence and pol gene-resistant mutations. From start to 8.5 months of MVC treatment only R5X4 viral clones were observed, whereas at 16 months the phenotype enlarged to also include R5 and X4 clones. Chimeric receptor usage suggested the preferential usage of the CXCR4 coreceptor by the R5X4 biological clones. According to phenotypic data, R5 viruses were susceptible, whereas R5X4 and X4 viruses were resistant to RANTES and MVC in vitro. Clones at 16 months, but not at baseline, showed an amino acidic resistance pattern in protease and reverse transcription genes, which, however, did not drive their tropisms. The geno2pheno algorithm predicted at baseline R5 viruses in plasma, and from 5.5 months throughout follow-up only CXCR4-using viruses. An extended methodological approach is needed to unravel the complexity of the phenotype and variation of viruses resident in the different compartments of an infected individual. The accurate evaluation of the proportion of residual R5 viruses may guide therapeutic intervention in highly experienced patients with limited therapeutic options.

Thirty-nine HIV-1-infected patients treated for 156 weeks with a new nucleoside analogue-sparing regimen [raltegravir, etravirine and maraviroc (REM) or raltegravir, etravirine and darunavir/ritonavir (RED)] showed a uniform increase in fasting glucose levels and a uniform decrease in insulin secretory capacity. Diabetes mellitus occurred in one RED-treated and four REM-treated patients. A worsening glucose tolerance was observed in highly treatment-experienced HIV-infected patients receiving effective antiretroviral therapy after virological failure.

Type 2 diabetes mellitus is a growing problem in HIV population and a comparison with the general population may help screening and prevention. In this cross-sectional study the authors determined the prevalence of type 2 diabetes mellitus in 4,249 HIV-infected subjects attending the San Raffaele Infectious Diseases Department compared with 9,148 healthy controls recruited in 15 Italian regions, and identified risk factors associated with of type 2 diabetes mellitus. Type 2 diabetes mellitus was defined as reported diabetes, a fasting plasma glucose concentration ≥7.0 mmol/l, or current use of anti-diabetic medication. Prevalence of type 2 diabetes mellitus was higher in HIV-infected than healthy subjects (4.1 vs. 2.5 %; P

Objective As a proactive diagnosis of diabetes mellitus (DM) may prevent the onset of severe complications, we used an oral glucose tolerance test (OGTT) to check for impaired glucose tolerance (IGT) and DM in patients with long-standing HIV infection and long durations of exposure to antiretroviral drugs with normal fasting plasma glucose (FPG) levels. Methods This was a cross-sectional, single-centre study. The homeostatic model assessment for insulin resistance (HOMA-IR) and 2-h post-load glucose levels were used to evaluate patients with known HIV-1 infection since before 1988 and no previous diagnosis of DM for whom data on hepatitis C virus (HCV) and hepatitis B virus (HBV) infection were available. Results Eighty-four Caucasian patients [67 (80%) male; median age 45.7 years; range 43.8–49.1 years] were able to be evaluated; 65 (77%) were coinfected with HCV, and seven (8%) were coinfected with HBV. Median (interquartile range [IQR]) exposure to antiretrovirals was 12.8 (10.4–16.5) years. Fifteen patients (18%) had a previous AIDS-defining event, 64 (76%) had HIV RNA

We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS ≥13 KPa. The diagnostic accuracy and optimal cut-off values, compared with LS categorization (13 vs ≥13 KPa), were determined by receiver operating characteristics (ROC) curves. The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (≥0.97 for APRI, ≥2.02 for FIB-4 and ≥7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases. The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co-infected patients, reducing the frequency of more expensive or invasive assessments.

Summary Background & aims We performed a cross-sectional study on adult HIV-infected patients, on HAART, without calcium or vitamin D supplementation to evaluate if the cardiovascular risk or the presence of osteoporosis may be predictive factors of an optimal daily calcium intake (DCI>1000 mg/day). Methods Patients underwent a dual-energy X-ray absorptiometry, measured biochemical parameters and compiled a validated questionnaire for the assessment of DCI. Osteoporosis (OP) was defined according to the WHO classification at either the vertebral spine or femoral neck. Cardiovascular risk was assessed by the 10-year Framingham cardiovascular risk score. Results 200 HIV-infected patients evaluated: 171 (86%) males with a median age of 48.1 (42.3–53.8) years and 10.6 (4.3–13.6) years of HAART exposure. DCI was 889 (589–1308) mg/day and 79 (40%) patients had an optimal DCI. Framingham risk>20% was found in 13 (6.7%) patients and femoral OP was diagnosed in 12 (6%) pts. By multivariate analysis, optimal DCI was more likely in patients with a Framingham risk>20% [OR = 5.547, 95% CI:1.337, p = 0.025] and less likely in patients with femoral osteoporosis [OR = 0.159, 95% CI: 0.018–0.790, p = 0.047]. Conclusions We found that an optimal dietary calcium intake was more likely in patients with high cardiovascular risk and no femoral osteoporosis.

Supplemental Digital Content is available in the text, Background: Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. Methods: This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible. We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography–mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. Results: HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. Conclusions: CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

Objectives Patients treated with maraviroc frequently show high CD4+ T cell increases. The aim of this study was to detail the characteristics of maraviroc-induced immune recovery. Patients and methods We studied T cell subsets from frozen peripheral blood mononuclear cells of patients treated with raltegravir, etravirine and either maraviroc (REM, n = 24) or darunavir/ritonavir (RED, n = 17). Results The two groups showed a similar decrease in activated CD4+ and CD8+ T cells. A greater loss of naive CD4+ T cells and a reduction in cells expressing CXCR4 were observed in REM patients, while RED patients showed a greater loss of cells expressing CCR5. Conclusions Our findings do not support a role for reduction in activated T cell subsets to explain the greater maraviroc-induced immune recovery. Reduction in CXCR4+CD4+ and higher expression of CCR5+CD4+ T cells might represent a potential protection from non-R5 tropic viral strain overgrowth.

Purpose of the study : To assess the impact of lamivudine (3TC) monotherapy in failing patients with multidrug-resistant HIV and limited therapeutic options. Methods: Prospective, open-label, multicenter, randomised (1:1), pilot study. HIV-1 failing pts with M184V mutation, HBsAg negative were assigned to 3TC 300mg QD for 24 weeks followed by a new regimen for 24 weeks (Arm A) or to a new regimen for 48 weeks (Arm B). The new HAART regimen was decided before randomisation in both groups, based on clinical history, genotype and viral tropism. Primary endpoint was the proportion of pts with HIV-RNA

Few data are available regarding the 10-year survival among subjects with HIV and cancer. The aim of this study was to evaluate the 10-year survival of HIV-infected subjects with AIDS-defining malignancies (ADM) or non-AIDS-defining malignancies (NADM). This was a single center, retrospective, observational study of subjects with HIV infection and a subsequent cancer diagnosis; the data were collected from January 1991 to April 2010. Malignancies were divided into ADM or NADM on the basis of the Centre of Diseases Control-1993 classification. Survival curves were estimated using Kaplan-Meyer method and compared by the log-rank test. Six hundred and fifteen (9.5%) of the 6,495 subjects recorded in the San Raffaele Infectious Diseases Database developed a malignancy: 431 (70%) an ADM and 184 (30%) a NADM. In the case of ADM, survival was more favorable when cancer was diagnosed during post-highly active antiretroviral therapy (HAART) era (10-year survival: 43.2% ± 4.4%) than when diagnosed during the pre-HAART era (10-year survival: 16.4% ± 2.7%; log-rank test: p < 0.001). The same was true in the case of NADM (10-year survival: 44.7% ± 5.5% vs. 33.3 ± 9.6%; log-rank test: p = 0.03). An evaluation of survival probability by cancer type showed higher survival rates during the post-HAART era in the case of non-Hodgkin lymphoma (10-year survival: 42.1% ± 5.3% vs. 11.4% ± 3.3%; log-rank test: p =

We prospectively evaluated 28 triple-class experienced HIV-1-infected patients harbouring R5 virus, who received maraviroc, raltegravir and etravirine. By on-treatment analysis, 26 (92%) had less than 50 copies HIV-RNA/ml at week 48. The median (interquartile range) 48-week increase in CD4 cell counts was 267 (136-355) cells/microl. Three serious adverse events occurred: one recurrence of mycobacterial spondylodiscitis, one anal cancer, one Hodgkin lymphoma. Although long-term safety needs further study, this protease inhibitor and nucleoside analogue-sparing regimen showed sustained efficacy.

The QRS interval of 56 out of 75 (74.7%) HIV-infected, drug-experienced patients (66.7% men) increased during treatment with boosted or unboosted atazanavir by a median 5 ms (interquartile range 0-9; P < 0.0001); the PR and the QTc intervals did not change significantly. New asymptomatic bundle branch blocks were observed in four patients; one subject with a baseline first-degree atriciventricular block developed symptomatic bradyarrhythmia while receiving atenolol. The electrocardiographic monitoring of patients treated with atazanavir seems advisable. The QRS interval of 56 out of 75 (74.7%) HIV-infected, drug-experienced patients (66.7% men) increased during treatment with boosted or unboosted atazanavir by a median 5 ms (interquartile range 0-9; P < 0.0001); the PR and the QTc intervals did not change significantly. New asymptomatic bundle branch blocks were observed in four patients; one subject with a baseline first-degree atriciventricular block developed symptomatic bradyarrhythmia while receiving atenolol. The electrocardiographic monitoring of patients treated with atazanavir seems advisable.

Objective: To evaluate the 24-week effects on glucose tolerance of switching from a protease inhibitor (PI)-based to an unboosted atazanavir-including regimen in highly pretreated HIV-1 infected subjects with metabolic alterations. Design: Prospective, open-label, single-center, 24-week pilot study. Methods: Twenty-one subjects underwent an oral glucose tolerance test (OGTT) at baseline (BL) and after 24 weeks of unboosted atazanavir. Insulin sensitivity and β-cell responsiveness were evaluated on the basis of static and dynamic data; fasting glucose, insulin, C-peptide, triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), TC/HDL-c ratio, CD4+ cell count and HIV-1 RNA were measured. Results: After 24 weeks of unboosted atazanavir, the 120-min glucose level was significantly lower than the one measured at BL (P=0.021); there were no statistically significant differences in the insulin concentration profile. The SIoral, an OGTT-based index of insulin sensitivity, was significantly higher at week 24 (P=0.017); the indices of first- and second-phase β-cell responsiveness did not significantly change. There was no significant difference between BL and 24-week fasting glucose, insulin or C-peptide levels, and consequently no change in fasting homeostasis model assessment indices of insulin sensitivity and β-cell function. There were significant improvements in TG (P=0.009), TC (P=0.0001), LDL-c (P=0.019) and TC/HDL-c ratio (P=0.001), and a similar trend in HDL-c levels (P=0.069). No significant changes in the immunological and virological parameters were detected. Conclusions: Our results show that switching from a PI-based to an unboosted atazanavir-including regimen leads to a significant improvement in glucose tolerance in highly pretreated HIV-1 infected subjects with metabolic alterations.

The objective of this study was to evaluate virological and pharmacological determinants of a 24-week virological response to unboosted atazanavir (ATV) in highly drug-experienced HIV-infected patients. Among patients enrolled in the ATV Expanded Access Program, those with HIV-RNA1000 copies/mL, a genotype performed within three months from the baseline (BL), and who completed 24 weeks of treatment, were included. They received at least three antiretrovirals, including ATV 400 mg once daily without boosting. ATV plasma levels were evaluated after four weeks of treatment by high performance liquid chromatography (HPLC). ATV genotypic inhibitory quotient (GIQ) was calculated as the ratio between ATV Ctrough and the number of the BL ATV-related protease resistance mutations (among the following: 10I/V/F, 20R/M/I, 24I, 331/F/V, 36I/L/V, 46I/L, 48V, 54V/L, 63P, 71V/T/I, 73C/S/T/A, 82A/F/S/T, 84V, and 90M). Thirty-five subjects were included. At baseline, median (interquartile range) CD4+ T-lymphocytes, HIV-RNA, and ATV resistance mutations were 232.5 (106-303)/microL, 4.7 (4.2-5.1) log10 copies/mL, 2 (1-6), respectively. Thirteen (37.1%) subjects were off-therapy and 11 (31.4%) showed no PI mutation at baseline. Median steady-state ATV Ctrough was 230 ng/mL (87-520), for an ATV GIQ of 86.5 (25.5-165.5). Median HIV-RNA changes from baseline at weeks 4, 12 and 24 were -1.76 (from -0.44 to -2.12), -1.41 (from -0.41 to -2.81) and -1.44 (from -0.42 to -2.71) log10, respectively. The HIV-RNA changes were correlated to the number of ATV resistance mutations at each time point (P0.05), whereas no correlation was found between ATV Ctrough or ATV GIQ and HIV-RNA changes. In conclusion, the number of ATV resistance mutations is the only correlate to virological response through 24 weeks of treatment with unboosted atazanavir 400 mg once daily.

Introduction : Unboosted atazanavir (ATV) including regimens have been investigated as a ritonavir-sparing simplification strategy. No data are available on removal of one NRTI in subjects effectively treated with unboosted atazanavir+2NRTIs. We present the 48-week virological efficacy and safety of unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC) (lamivudine/emtricitabine/Reyataz © , LAREY Study). Materials and Methods : Single arm, prospective, pilot study on HIV-treated patients, HBsAg negative, with HIV-RNA 50 cps/ml; viral blip was defined as a single HIV-RNA value>50 cps/ml not subsequently confirmed. Results as median (IQR). Changes between baseline (BL) and week 48 assessed by the Wilcoxon signed rank test. Results : Forty patients enrolled: 75% males, 51 (47–54) years, 14% HCV co-infected, infected with HIV since 16 (9–21) years, on antiretroviral therapy since 13 (5–16) years, with a nadir CD4+ of 254 (157–307) cells/mm 3 , virologically suppressed since 4.2 (2.2–5.4) years; 53 patients switched from a tenofovir (TDF)-based regimens; ATV was associated with 3TC in 83% patients. No virological failures or discontinuations were observed; three patients had a single viral blip in the range 50–250 copies/mL; CD4+ increased from 610 (518–829) cells/mm 3 at BL to 697 (579–858) cells/mm 3 at week 48 [48-week change: 39 (−63/+160) cells/mm 3 p=0.081]. Three clinical events were observed (one herpes zoster, one pneumonia, one syphilis) in absence of renal lithiasis, AIDS-defining or drug-related events or death. Overall, significant 48-week amelioration of ALP [BL: 83 (71–107) mg/dL; 48-week change: −15 (−27/−8) mg/dL p

Methods We decided to simultaneously screen triple class failing patients (pts) followed at San Raffaele Hospital in three Expanded Access Programs: raltegravir (MK0518-023), maraviroc (A4001050), etravirine (TMC125-C214). Salvage therapy was prescribed according to: viral tropism, screening genotype and previous resistance tests. Data were collected at baseline (BL) and at 4, 12, 24, 36 and 48 weeks. Generalized linear regression model was applied. Results are reported as median (Q1–Q3).

Diagnosis of schistosomiasis in migrants coming from endemic areas can be difficult, especially in asymptomatic subjects. Light-intensity disease, in fact, may be missed due to the low sensitivity of the stool microscopy and serologic testing cannot distinguish between a resolved infection and an active infection in patients who have been infected and treated in the past, because specific antibodies can persist despite cure. We describe a cross-sectional study conducted on 82 migrants tested for Schistosoma mansoni on single blood (anti-schistosome antibodies, total IgE) and urine [point-of-care (POC) circulating-cathodic-antigen (CCA) test] samples. A positive POC-CCA test (active infection) resulted in two untreated patients with a positive serology while all patients (n = 66) with a past infection showed a negative POC-CCA test. POC-CCA urine test in combination with serology may be helpful in rapidly differentiate active from past S. mansoni infection in migrants coming from endemic areas.

We determined the prevalence of type-2 diabetes mellitus (DM) in HIV infected (HIV+) and uninfected (HIV-) subjects. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P230 Cite this article as: Galli et al.: Prevalence of type 2 diabetes mellitus and its predictive factors in Italy: a comparison between HIV-infected and uninfected subjects. Journal of the International AIDS Society 2010 13 (Suppl 4):P230. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113017/