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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

Abstract Total cell-associated HIV-1 DNA is a surrogate marker of the HIV-1 reservoir, however, certified systems for its quantification are not available. The Italian HIV DNA Network was launched to validate HIV-1 DNA quantification methods in use at University and Hospital labs. A quality control panel including HIV-1 DNA standards, reconstructed blood samples (RBSs) and DNA from different HIV-1 subtypes was blindly tested by 12 participating labs by quantitative real-time PCR (n = 6), droplet digital PCR (n = 3) or both (n = 3). The median 95% hit rate was 4.6 (3.7–5.5) copies per test and linearity in the tested range was excellent (R2 = 1.000 [1.000–1.000]). The median values obtained across labs were 3,370 (2,287–4,245), 445 (299–498), 59 (40–81) and 7 (6–11) HIV-1 DNA copies, for the 3,584, 448, 56 and 7-copy standards, respectively. With RBSs, measured values were within twofold with respect to the median in two thirds of cases. HIV-1 subtypes were missed (CRF01_AE by 3 labs) or underestimated by > 1 log (subtypes A, C, D, F by one lab; CRF01_AE by one lab; CRF02_AG by one lab). The overall performance was excellent with HIV-1 DNA standards, however detection of different HIV-1 subtypes must be improved.

Abstract Introduction Long-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated. Methods In this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection. Results We included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA

Background: HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients. Objective: To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid–binding protein (I-FABP) and D-dimer. Methods: We performed a retrospective case-crossover study on integrase inhibitors-naïve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for ≥48 weeks who switched to 3TC + DTG and maintained this regimen for ≥48 weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48 weeks before (−48 W) and 48 weeks after switch (+48 W). Results: A total of 67 patients were included. Median sCD14 levels were stable from −48 W to BL (from 6.07 to 6.04 log10 pg/mL, p = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84–6.07) log10 pg/mL at + W48 (p

Abstract Background Direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking. Methods Time to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated. Results Four-hundred-ninety-four patients were analyzed (170 switching to darunavir/r, 141 to atazanavir/r, 183 to dolutegravir): median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching. Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (p

The focus of this review is to examine the importance of quantifying total HIV DNA to target the HIV reservoir and the clinical implications and challenges involved in its future application in clinical practice. Despite intrinsic limitations, the quantification of total HIV DNA is currently the most widely used marker for exploring the HIV reservoir. As it allows estimating all forms of HIV DNA in the infected cells, total HIV DNA load is the biomarker of the HIV reservoir that provides most of the insights into HIV pathogenesis. The clinical role of total HIV-DNA in both untreated and treated patients is extensively supported by important lines of evidence. Thus, predictive models that include total HIV DNA load together with other variables could constitute a prognostic tool for use in clinical practice. To date, however, this marker has been primarily used in experimental evaluations. The main challenge is technical. Although the implementation of droplet digital PCR could improve analytical performance over real-time PCR, the lack of standardization has made cross-comparisons of the data difficult. An effort by investigators to compare protocols is needed. Furthermore, the main effort now should be to involve the biomedical industry in the development of certified assays for in vitro diagnostics use.

Background: this study aimed to determine the proportion of people living with HIV (PLWH) with anti-SARS-CoV-2 IgG antibodies in a large sample from a single HIV referral center in Rome, Italy; the time-frame included both the first and the second wave of the Italian COVID-19 pandemic; Methods: we conducted a cross-sectional study on stored cryopreserved samples from 1 March 2020 to 30 November 2020. Total antibodies against SARS-CoV-2 were preliminarily tested using a chemiluminescent immunoassay. Positive results were re-tested with an ELISA assay as an IgG confirmatory test; Results: overall, 1389 samples were analyzed from 1106 PLWH: 69% males, median age 53 years, 94% on antiretroviral treatment, 93% with HIV-RNA < 50 copies/mL, median CD4 cell count 610 cell/µL. Our analysis revealed a total of n = 8 patients who tested IgG positive during the study period. Seroprevalence was equal to 0% in the first months (March–June); this started to increase in July and reached a maximum rate of 1.59% in October 2020. The overall seroprevalence was 0.72% (8/1106, 95% CI 0.37–1.42). Conclusion: our findings from this setting show a low IgG SARS-CoV-2 prevalence among PLWH as compared to data available from the general population.

Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) versus the 23-valent polysaccharide vaccine (PPSV23) in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50) received two doses of PCV13 eight weeks apart, and group 2 (n = 50) received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100) were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.