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Our study assessed the CD4+/CD8+ ratio in people with HIV (PWH) switching from a second-generation integrase inhibitor regimen to long-acting cabotegravir (CAB) and rilpivirine (RPV). Over one year, we observed a significant improvement in the CD4+/CD8+ ratio; In addition, our data showed that time spent in CAB+RPV was significantly associated with an increased CD4+/CD8+ ratio. These findings suggest that long-acting therapy may enhance immune recovery, also in treatment-experienced PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Impairment of the gastrointestinal barrier leads to microbial translocation and peripheral immune activation, which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely and chronically-infected, combination antiretroviral therapy (cART)-naive individuals., Methods: Fifteen people with primary HIV infection (P-HIV) and 13 with chronic HIV infection (C-HIV) c-ART-naive participants were cross-sectionally studied. Gut biopsies were analysed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 + expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3 + panγδ+Vδ1+/Vδ2+). In plasma, we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA)., Results: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared with C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV., Conclusion: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely because of a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The study aim was to evaluate whether mpox vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN) may be associated with viral blips or confirmed virologic failures (CVF) in people with HIV (PWH) receiving antiretroviral therapy and the associated factors., Design: PWH who received MVA-BN, with HIV-RNA less than 50 copies/ml, and CD4 + lymphocytes at least 200 cells/μl in the 6 months prior to vaccination and at least 1 HIV-RNA determination within 3 months from vaccination., Methods: The primary outcome was occurrence of viral blips (1 HIV-RNA ≥50 copies/ml) and CVF (1 HIV-RNA ≥1000 copies/ml or ≥2 consecutive HIV-RNA ≥50 copies/ml) following MVA-BN. Changes in CD4 + and CD4 + /CD8 + were secondary outcomes. Residual viremia was defined as detectable HIV-RNA less than 50 copies/ml. PWH already vaccinated against smallpox received single-dose MVA-BN. Mann--Whitney rank-sum test or chi-square/Fisher's test applied., Results: Overall, 187 PWH were included: 147 received two doses of MVA-BN, 40 single-dose. Six viral blips [incidence rate = 1.59/100-person months of follow-up (PMFU), 95% confidence interval (95% CI) = 0.58-3.47], and three CVFs [incidence rate = 0.80/100-PMFU (95% CI = 0.16-2.33)] were observed. Two CVFs occurred at second dose with presence of detectable HIV-RNA following first one, with high compliance to antiretroviral therapy (ART). PWH with viral blips or CVFs had, prior to first vaccination, more frequently residual viremia [77% ( n  = 7) versus 35% ( n  = 62), P  = 0.01]. No differences in ART ( P  = 0.42) and number of MBA-BN doses ( P  = 0.40) was found. In two cases of CVFs, ART was changed; all VBs resolved within 1 month., Conclusion: Although rare, viral blips and CVFs following MVA-BN vaccination among PWH receiving ART were identified. Close monitoring of HIV-RNA during mpox vaccination should be encouraged., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Aims of this study were to assess the characteristics of Mpox among people with HIV (PWH) and describe the change of some immune-virological parameters during Mpox virus infection., Design: Case series of PWH diagnosed with Mpox between May and July 2022 at the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy., Methods: Real-time PCR was used to detect Mpox virus on oropharyngeal, cutaneous, genital and rectal swabs, plasma, seminal fluids, and urines. The values of the CD4 + lymphocytes and HIV-RNA were assessed both at Mpox diagnosis and after Mpox virological clearance and were compared to those prior to Mpox. The relationship between the symptoms clinical duration of Mpox and the CD4 + cell count at diagnosis was assessed with Spearman's correlation coefficient., Results: Overall, 28 PWH on antiretroviral therapy with Mpox were evaluated. HIV-RNA did not substantially change at Mpox infection with respect to previous virological profile ( P  = 0.721). However, at time of Mpox diagnosis, we observed a detectable HIV-RNA (196 copies/ml) in one individual previously undetectable (HIV-RNA < 20 copies/ml) and an increase to 1.220 copies/ml in a previously viremic subject (HIV-RNA = 263 copies/ml). No significant differences in CD4 + cell count were found before and at time of Mpox diagnosis ( P  = 0.151) and a higher CD4 + cell count at Mpox diagnosis was marginally related to a lower duration of Mpox symptoms ( r  = -0.341, P  = 0.068)., Conclusions: Among PWH, we advise monitoring HIV viral load at Mpox diagnosis and during follow-up, as well as providing counseling on the results, due to the important individual and community implications., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

To evaluate patients' expectations regarding long-acting antiretroviral agents and preferences about where to receive them. Multicenter cross-sectional survey-based study. Through an online survey, we asked people living with human immunodeficiency virus to judge their relationship with daily antiretroviral therapy (ART) and to give their opinion about long-acting drugs. We also collected data regarding the age of the patients, their site of follow-up, time since the diagnosis, and compliance to ART. Two hundred forty-two patients aged 18 to 79 years were included in the study: 58 (24%) females, 182 (75.2%) males, and 2 (0.8%) male-to-female transgenders. 81.8% of the said population had a good relationship with ART. 33.6% of them consider daily ART an obligation and a restriction to their freedom. One hundred forty-three (59.1%) patients already knew about long-acting drugs before our interview, and 215 (88.8%) patients were interested in it. One hundred fifty-six (64.4%) interviewees said they would still be interested in hospital-available injective long-acting drugs, although 57.9% of the patients would rather receive them at home. The data emerging from our survey reveal that around 90% of the people living with HIV are interested in changing their actual treatment with a long-acting one. Moreover, for the first time to our knowledge, such a high number of patients showed an enthusiastic response to the new opportunity to be treated directly at home. The introduction of these new drugs could be revolutionary and represents an important step toward treatment simplification., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

In this randomized, single-centre, open-label, 96-week, superiority, controlled trial of 50 HIV-infected patients with HIV-RNA less than 50 copies/ml on a two-drug regimen based on dolutegravir as well as one reverse transcriptase inhibitor (RTI), switching to a single-tablet regimen of cobicistat, elvitregravir, emtricitabine along with tenofovir alafenamide did not appear to mitigate the burden of residual viremia, both at week 48 and at week 96. The immunological changes observed during follow-up and the safety of the two regimens were similar., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to explore weight gain in people with HIV (PWH) at least 65 years of age who switch to a DTG based regimen (DTG-s) vs. remaining INSTI-naive (INSTI-n) on stable ART., Methods: This was a longitudinal prospective study of PWH from the GEPPO cohort. At the beginning of the observational period, participants were INSTI-naives (INSTI-n). During follow-up, they were divided in two groups: INSTI-n vs. dolutegravir-switchers (DTG-s) with no further change in ART. Body weight was assessed at baseline and at last follow-up visit. Significant weight gain was defined as an increase at least 5% of baseline weight from the first to the last visit. ART regimens were collected at each patients' visit. Kaplan--Meier curves were drawn to assess time to reach a weight gain more than 5%., Results: Out of 568 PWH (83.1% men, median age 69.5 years), 427 (75%) were INSTI-n and 141 (25%) DTG-s. After an average follow-up of 2.6 (±0.8) years, no significant change in body weight was observed both among INSTI-n [delta weight = 0.02 (±7.5), P = 0.633] and DTG-s [delta weight = -0.04 (±5.2), P = 0.755]. Weight gain was also not significantly different between study groups (9.3% in INSTI-n and 15.1% in DTG-S: P = 0.175). No significant differences in time to achieve a weight gain greater or equal than 5% of baseline weight emerged in INSTI-n vs. DTG-s (P = 0.93), two-drug regimens (2DR) vs. three-drug regimens (3DR) (P = 0.56) or TAF vs. TDF (P = 0.56)., Conclusion: Results from a large Italian cohort did not show a significant weight gain associated with switch to DTG in PWH 65 years of age or older. This finding emerged also when comparing 3DR vs. 2DR and TAF exposed and unexposed geriatric PWH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coronary artery disease (CAD) is one of the leading causes of death among people living with HIV (PLWH). We evaluated ECG stress testing (EST) for detecting CAD in PLWH with multiple cardiovascular risk factors., Methods: CORDIS was a cross-sectional study conducted in PLWH. Inclusion criteria were men at least 50 years or postmenopausal women, HIV-1 RNA less than 50 copies/ml and at least one of the following cardiovascular risk factor: familial history of CAD, smoking, hypertension, hypercholesterolemia or diabetes. Patients with a previous diagnosis of CAD or with cardiac symptoms were excluded. EST was performed concomitantly with bilateral carotid color-Doppler ultrasonography (CDU) and evaluated by a cardiologist. Results were described by median (interquartile range) or frequency (%). Logistic regression was applied to evaluate predictive factors of inducible myocardial ischemia (IMI)., Results: EST and CDU were performed in 309 individuals; IMI prevalence was 7.4% [95% confidence interval (CI): 5.0-11.0%]. Among patients with a normal CDU, no cases of IMI were observed. In people with abnormal CDU, IMI prevalence increased accordingly with the atherosclerotic cardiovascular disease (ASCVD) risk score: 10.2%, 16.9%, 19.7%, 27.8% and 30.4% among individuals with ASCVD score 7.5% or less, more than 7.5%, more than 10%, more than 15% and more than 20%, respectively (P for trend: 0.02). At multivariate analysis, ASCVD risk score was associated with EST suggestive of IMI (adjusted odds ratio for 1% increase = 1.08; 95% CI: 1.02-1.13, P = 0.005) and with confirmed IMI (adjusted odds ratio for 1% increase = 1.11; 95% CI: 1.04-1.19, P = 0.003)., Conclusion: Prevalence of IMI was 7.4% in the CORDIS study. We suggest EST as first-line screening for CAD in PLWH without cardiac symptoms, with an abnormal CDU and a high ASCVD risk score., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Very limited data are available on the immunovirological outcomes after 13-valent pneumococcal conjugate vaccine (PCV13) in antiretroviral therapy (ART)-treated patients. The aim of this study was to assess the immune-virological outcomes in HIV-1-infected ART-treated patients on stable virological suppression who underwent pneumococcal conjugate vaccination., Methods: Retrospective, cohort study on ART-treated HIV-1-infected individuals, age at least 18 years, with three consecutive determinations of HIV-RNA less than 50 copies/ml before the administration of PCV13 (baseline) at San Raffaele Hospital and with at least two HIV-RNA values after vaccination., Results: Overall 1197 patients underwent PCV13 vaccination. During 6-month of follow-up (594 person-years of follow-up, PYFU), 12 confirmed virological failure and 35 viral blips were observed; the overall incidence rate of confirmed virological failure was 2.02 (95% confidence interval: 0.88-3.16) per 100-PYFU and the incidence rate of viral blips was 5.89 (95% confidence interval: 3.94-7.84) per 100-PYFU. Median CD4 cell count change from baseline at 6 months was +10 cells/μl (interquartile range -67, +111; P = 0.0002). Median change in CD4/CD8 ratio was +0.02 (interquartile range -0.06, +0.11; P < 0.001)., Conclusion: Viral blips and confirmed virological failures were rarely observed in patients on stable virological suppression in the first 6 months following vaccination with PCV13. In addition, no decrease of CD4 cell count and CD4/CD8 ratio was recorded.

Objective: The frequency of immature transitional B cells is increased in blood of HIV-1-infected individuals. We investigated whether HIV-1 infection affects expression and function of chemokine receptors important for egress of immature transitional B cells from bone marrow and migration to lymphoid organs., Design: This is a cross-sectional study analysing the migratory phenotype and function of immature transitional B cells in HIV-1-infected individuals, in relation to antiretroviral treatment and age., Methods: Frequency of blood immature transitional B cells and their phenotypic characteristics, including chemokine receptors and a maturation marker, were determined by immunostainings. Migratory capacities were studied in a migration assay., Results: The increased frequency of immature transitional B cells in untreated HIV-1 infection was normalized in patients receiving antiretroviral treatment; in our cohorts, age did not have an impact on the frequency of circulating immature transitional B cells. Immature transitional B cells from nontreated patients expressed low levels of CD21 molecule. We found an elevated frequency of CXCR3 and CXCR4 expressing immature transitional B cells in treated and nontreated patients. CXCR4 receptor was unresponsive to CXCL12 ligand in in-vitro migration and internalization assays. In addition, CXCR5 expression was downregulated on immature transitional B cells from infected patients, and these cells migrated poorly in response to CXCR5 ligand., Conclusion: Circulating immature transitional B cells from HIV-1-infected patients are not fully mature, probably due to premature egress from bone marrow; these cells showed a phenotype which could impair entry into secondary lymphoid organs. Changes in migratory capacity of immature transitional B cells may affect B-cell maturation during HIV-1 infection.

Objective: The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral-naive HIV-1 infected individuals., Design: MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretroviral-naive adults with plasma HIV-1 RNA at least 1000 copies/ml and no evidence of reduced susceptibility to study drugs., Methods: At screening, participants were randomized 1 : 1 to undergo either genotypic or phenotypic tropism testing. Participants with CCR5-tropic HIV-1 were randomized 1 : 1 to receive maraviroc 150 mg once daily or tenofovir/emtricitabine once daily each with darunavir/ritonavir once daily for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml (Food and Drug Administration snapshot algorithm) at Week 48. A substudy evaluated bone mineral density, body fat distribution and serum bone turnover markers., Results: Seven hundred and ninety-seven participants were dosed (maraviroc, n = 396; tenofovir/emtricitabine, n = 401). The Data Monitoring Committee recommended early study termination due to inferior efficacy in the maraviroc group. At Week 48, the proportion of participants with HIV-1 RNA less than 50 copies/ml was 77.3% for maraviroc and 86.8% for tenofovir/emtricitabine [difference of -9.54% (95% confidence interval: -14.83 to -4.24)]. More maraviroc participants discontinued for lack of efficacy, which was not associated with non-R5 tropism or resistance. Discontinuations for adverse events, Category C events, Grade 3/4 adverse events and laboratory abnormalities were similar between groups., Conclusion: A once-daily nucleos(t)ide-sparing two-drug regimen of maraviroc and darunavir/ritonavir was inferior to a three-drug regimen of tenofovir/emtricitabine and darunavir/ritonavir in antiretroviral-naive adults.

The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was observed in adjusted eGFR slopes between patients receiving DRV/r and those receiving LPV/r. In the 286 patients treated with ABC and lamivudine, eGFR slopes were similar, independent of the PI.In patients receiving TDF/xTC, eGFR trajectories were small for all regimens and declined less in patients receiving DRV/r or NNRTIs than in those treated with ATV/r or LPV/r.

Objective: Previous studies have shown that statins use is associated with a lower mortality risk or occurrence of non-Hodgkin's lymphoma or non-AIDS-defining malignancies (NADMs) in HIV-positive patients. We evaluated the effect of statin therapy on the occurrence of all AIDS-defining malignancy (ADM) and NADM among HIV-positive patients., Design: A chart study on HIV-1 infected patients attending the Infectious Diseases Department of the San Raffaele Scientific Institute, Italy., Methods: Incident malignancies diagnosed since antiretroviral treatment (ART) initiation until October 2012 among treated patients not taking statins at ART initiation. Statin therapy had to precede cancer diagnosis, if it occurred. Malignancies that occurred before ART or statin initiation were excluded. Follow-up was calculated since ART initiation until the first cancer diagnosis or loss to follow-up or death or last available visit, whichever occurred first. Results are described as median (interquartile range, IQR)., Results: Five thousand, three hundred and fifty-seven HIV-1 treated patients were included. During 52 663 person-years, 740 (14%) patients had a history of statin use; 375 malignancies occurred: 12 (1.6%) malignancies (0 ADM; 12 NADM, crude incidence rate, 1.3/1000 person-years) among statin users and 363 (7.9%) malignancies (194 ADM; 169 NADM, crude incidence rate, 8.4/1000 person-years) among non-statin users. By multivariate Fine-Gray regression, statin use was associated with a lower risk of cancer [adjusted hazard ratio (95% confidence interval) for ever use: 0.45 (0.17-0.71)]., Conclusion: Among HIV-1 treated patients, statin use was associated with a lower risk of cancer; the benefit was mainly related to AIDS-defining malignancies. Confirmatory studies are needed to consider the residual confounding likely present in this study., (2014 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml., Methods: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100 mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification., Results: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with two NRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with two NRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification = failure), treatment success was 73% in ATV/r arm and 85% in ATV/r along with two NRTIs [difference -12.1%, 95% confidence interval (95% CI) -27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92% in ATV/r arm and 85% in the ATV/r along with two NRTIs arm (difference 7.5%, 95% CI -4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P = 0.003) and grade 3-4 drug-related (P = 0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)-cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs., Conclusion: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.

Objectives: During HIV-1 infection, the development, phenotype, and functionality of B cells are impaired. Transitional B cells and aberrant B-cell populations arise in blood, whereas a declined percentage of resting memory B cells is detected. Our study aimed at pinpointing the demographic, immunological, and viral factors driving these pathological findings, and the role of antiretroviral therapy in reverting these alterations., Design: B-cell phenotype and correlating factors were evaluated., Methods: Variations in B-cell subsets were evaluated by flow cytometry in HIV-1-infected individuals naive to therapy, elite controllers, and patients treated with antiretroviral drugs (virological control or failure). Multivariable analysis was performed to identify variables independently associated with the B-cell alterations., Results: Significant differences were observed among patients' groups in relation to all B-cell subsets. Resting memory B cells were preserved in patients naive to therapy and elite controllers, but reduced in treated patients. Individuals naive to therapy and experiencing multidrug failure, as well as elite controllers, had significantly higher levels of activated memory B cells compared to healthy controls. In the multivariate analysis, plasma viral load and nadir CD4 T cells independently correlated with major B-cell alterations. Coinfection with hepatitis C but not hepatitis B virus also showed an impact on specific B-cell subsets. Successful protracted antiretroviral treatment led to normalization of all B-cell subsets with exception of resting memory B cells., Conclusion: Our results indicate that viremia and nadir CD4 T cells are important prognostic markers of B-cell perturbations and provide evidence that resting memory B-cell depletion during chronic infection is not reverted upon successful antiretroviral therapy.

Objective: to determine the immunogenicity of the monovalent vaccine against 2009 pandemic influenza A/H1N1 in HIV-1-infected individuals., Design: a total of 192 participants, including 44 HIV-1-positive individuals and 148 HIV-1-negative healthy controls were enrolled to receive a single dose of MF59-adjuvanted 2009 A/H1N1v vaccine formulated to contain 7.5 microg of haemagglutin antigen., Methods: standard haemagglutination inhibition (HAI) assay was performed to evaluate seroconversion and seroprotecsion rates against the pandemic virus in serum samples collected at baseline (T0) and 3-5-week postvaccination (T28). Seroconversion to vaccination was defined by either prevaccination HAI titer less than 1: 10 with a postvaccination titer higher than 1: 40, or a prevaccination titer higher than 1: 10 and increase of at least four-fold or more after vaccination. Seroprotection was defined by HAI titers higher than 1: 40., Results: the vaccine induced specific antibody titers in HIV-1-positive individuals similar to those of HIV-1-negative controls [215.3, 95% confidence interval (CI) 150.4-308.1 vs. 275.9, 95% CI 232.6-327.3] with postvaccination seroprotection rates higher than 97%. In contrast, the seroconversion rate was lower in the HIV-1-positive individuals as compared with the HIV-1-negative controls (36.4 vs. 79.0%, P < 0.0001), likely as a consequence of their high HAI baseline titers. Multivariable logistic regression analysis showed that seroconversion was less likely in HIV-1-positive individuals [odds ratio (OR) = 0.237, 95% CI 0.104-0.539, P = 0.0006) and with increasing age (OR = 0.805, 95% CI 0.684-0.947, P = 0.009)., Conclusions: a single dose of MF59-adjuvanted 2009 influenza H1N1 vaccine induced an immune response against pandemic H1N1 virus in HIV-1-positive individuals reaching titers similar to those of HIV-1-negative individuals. The seroconversion rate was negatively associated with HIV infection and increasing age., (2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.)

Background: Organic anion transporting polypeptides (OATPs) are emerging as major determinants of pharmacokinetics for numerous drugs, with the 1B1 isoform-mediating hepatic uptake. The 521 T>C polymorphism has been correlated earlier with higher plasma concentrations of several drugs and the aim of this study was to determine whether this polymorphism influences trough concentrations of maraviroc., Methods: The uptake of maraviroc by OATP1B1 was assessed using a heterologous Xenopus laevis oocyte expression system and quantified using a novel liquid chromatography-mass spectrometry method. Regression analyses were conducted to identify factors associated with maraviroc Ctrough in 59 patients treated with maraviroc at 150, 300, or 600 mg twice daily., Results: Maraviroc was identified as a substrate for OATP1B1 with a Km of 33.9 μmol/l. A dose of 600 mg of etravirine or efavirenz [odds ratio (OR) = 0.22, 95% confidence interval (95% CI): 0.06-0.76; P = 0.016] and SLCO1B1 521 heterozygosity were both associated with maraviroc Ctrough, above the suggested target concentration of 50 ng/ml (OR = 20.3, 95% CI: 2.2-182; P = 0.007)., Conclusion: These findings show the importance of OATP1B1 for variability in maraviroc pharmacokinetics. Furthermore, the SLCO1B1 521 T>C polymorphism maybe useful in predicting higher plasma concentrations but these data should be confirmed before prospective clinical studies to define the clinical usefulness.

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.

Genotypes in nine highly protease inhibitor (PI)-experienced patients were studied before and after lopinavir/ritonavir (LPV/r) treatment. Resistance to amprenavir was the rule both before and after LPV/r treatment. Treatment with LPV/r can select for the 50 V mutation. In this setting, significant differences in the inference of the amprenavir phenotype from genotype were observed when using different algorithms.

Objective: To verify whether the in vitro sensitivity of immature dendritic cells (iDC) to lysis by autologous natural killer (NK) cells from HIV-infected individuals might be correlated with HIV disease progression., Design: Both dendritic cells (DC) and interlekin (IL)-2 activated NK cells were obtained from 13 HIV-infected individuals early after seroconversion and not receiving highly active antiretroviral therapy (HAART) and from 14 individuals with chronic HIV infection under HAART. The rate of NK cell-mediated killing of autologous iDC was correlated with classical parameters of HIV evolution., Methods: Peripheral blood monocytes obtained from the Ficoll-derived leukocyte fraction after adherence to plastic were stimulated with granulocyte-macrophage colony stimulating factor plus IL-4 to induce their differentiation into iDC to be used as target cells in a standard 4-h cytotoxicity assay. A fraction of autologous leukocytes was stimulated with IL-2 to induce activation of NK cells to be used as effector cells., Results: During early HIV infection the extent of ex vivo lysis of monocyte-derived DC by activated autologous NK cells was inversely and directly correlated with the levels of viraemia and with the percentage of circulating CD4 T cells, respectively. In contrast, the capacity of NK cells to kill iDC was lost independently of the levels of plasma viraemia or the concurrence of HAART in chronically infected individuals. Addition of exogenous HIV Tat during the cytotoxicity assay inhibited NK cell-mediated lysis of DC., Conclusions: NK cell-mediated immune surveillance against infected DC may be effective only during early HIV infection and may not be restored by HAART.

Objective: In HIV-positive individuals administration of intermittent interleukin (IL)-2 in addition to highly active antiretroviral therapy (HAART) induces expansion of the peripheral T cell pool with dilution of signal joint T cell receptor excision circles (sjTREC) that cannot be used to measure thymic output. We analysed whether in vitro thymopoiesis could be used to predict in vivo thymic output in IL-2 treated subjects., Design and Methods: We correlated the relative variation of peripheral CD4 T cells over 12 months in HIV-positive subjects on HAART or HAART + IL-2 with the mean levels of both sjTREC and T cells developed in chimeric murine foetal thymic organ cultures (FTOC) reconstituted with circulating progenitors., Results: In contrast with HAART treated individuals in which these values were directly correlated, in subjects receiving HAART + IL-2 the increase of CD4 T cells in vivo was correlated to neither sjTREC number nor to reconstitution of FTOC, probably reflecting a main effect of IL-2 in the expansion of the peripheral T cell pool. Nevertheless, addition of IL-2 to HAART determined a significant increase of in vitro thymopoietic potential in individuals with undetectable viraemia., Conclusions: The increased T cell development in vitro after addition of IL-2 to HAART suggests that intermittent IL-2 administration may exert a positive influence on lymphopoiesis. In two subjects with positive viraemia treated with IL-2 we observed reduced in vitro development of T cell precursors suggesting that the positive influence of IL-2 on thymopoiesis could be secondary to the control of viral replication by HAART. These observations provide novel evidence in support of the potential beneficial use of IL-2 in HAART treated individuals.