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Objectives Few studies have investigated chronically infected individuals after antiretroviral therapy (ART) interruption (ATI, analytical therapy interruption); thus, we investigated the association between some HIV-specific antibodies and viral control. Design All enrolled patients were previously described in the APACHE study. Briefly, the study was conducted on HIV-1 chronically infected patients, with HIV-RNA less than 50 copies/ml for at least 10 years, CD4+ cell count greater than 500 cells/μl and HIV-DNA less than 100 copies/106 PBMC. The ART regimen in use at the time of ATI was resumed at confirmed viral rebound (CVR, defined as two consecutive HIV-RNA >50 copies/ml). Methods Collection of sera and analysis of both binding antibodies (BAbs) and neutralizing antibodies (NAbs) was performed at three different time points: ATI, CVR and time of viral re-suppression after ART resumption. Results IgG subclasses (IgG1, IgG2, IgG3 and IgG4) from the four patients with highest levels of neutralization were found to block viral infection. All patients had CVR after ATI at a median time of 21 days (14-56). After ART resumption, all the enrolled patients achieved HIV-RNA less than 50 copies/ml in 42 days (21-98). We observed a strong increase of either BAbs and NAbs titers from ATI to viral re-suppression in one patient, who showed the longest period of virus undetectability during ATI. In this patient, BAbs and NAbs specifically belonged to both IgG1 and IgG4 subclasses, directed to env antigen. Conclusion env-specific NAbs and BAbs belonging to IgG1, IgG4 subclasses could be helpful to monitor long-term responses able to control virus replication and eradicate HIV infection.

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(S):. Tripartite motif-containing 22 (TRIM22) is an interferon-induced protein that inhibits HIV-1 transcription and replication in vitro. Two single nucleotide missense polymorphisms rs7935564A\/G (SNP-1) and rs1063303C\/G (SNP-2) characterize the coding sequence of human TRIM22 gene. We tested whether these variants affected the inhibitory effect of TRIM22 on HIV-1 replication and transcription and their potential association with HIV-1 disease.. DESIGN:. The allelic discrimination was determined in 182 HIV-1-negative and among HIV-1-positive individuals with advanced disease progression (advanced progressors; n = 57), normal progressors (n = 76), and long-term nonprogressors (LTNPs; n = 95).. METHODS:. Renilla luciferase activity was measured after infection of activated peripheral blood mononuclear cells (PBMCs) from an additional group of 61 blood donors with a recombinant HIV-1. HIV-1-long terminal repeat (LTR)-driven luciferase activity was tested in the presence of plasmid expressing TRIM22 variants in 293T cells. The SNP genotyping was determined by TaqMan assay.. RESULTS:. HIV-1 replication was more efficient in PBMCs from donors with SNP-1G and SNP-2G than from those with SNP-1A and SNP-2C alleles. Consistently, TRIM22-GG enhanced, whereas TRIM22-AC restricted basal HIV-1 LTR-driven transcription. In vivo, SNP-1G homozygotes and A\/G heterozygotes were more frequent in advanced progressors than in LTNPs [odds ratio (OR) = 2.072, P = 0.005] or in normal progressors (OR = 1.809, P = 0.022); in contrast, SNP-2 was not associated with any state of HIV-1 disease progression. Although SNP-2 distribution was similar among the groups, TRIM22-GG haplotype was found more frequently in advanced progressors than in LTNPs (P = 0.02).. CONCLUSION:. TRIM22 genetic diversity affects HIV-1 replication in vitro and it is a potentially novel determinant of HIV-1 disease severity."

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. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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.

The best salvage therapy for protease inhibitor (PI)-resistant HIV-infected patients is still controversial. We measured changes in viral load and CD4 T-lymphocyte counts in 40 PI-resistant patients receiving boosted PI-including or PI-sparing antiretroviral therapy. At multivariate analysis, the only independent predictor of CD4 T-lymphocyte changes at week 24 was a boosted PI-including regimen. In PI-resistant HIV-infected patients, a boosted PI regimen preserves CD4 T lymphocytes from depletion in the medium term compared with a PI-sparing regimen.