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In our population, NNRTI-based HAART seems to have a stronger impact on residual replication than protease inhibitor-based HAART. This finding may be considered in therapeutic decisions such as the choice of initial HAART regimen and the interruption or simplification of treatment.

Summary Background Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. Aim To investigate the impact of direct‐acting antiviral treatment on microbial translocation and T‐cell activation, in patients with hepatitis C‐related liver disease. Methods We enrolled two groups of HCV‐infected patients undergoing direct‐acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct‐acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble‐CD14, lipopolysaccharide‐binding protein and intestinal fatty acid‐binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T‐cell activation was measured by expression of CD38+ HLA‐DR at the same time points, only in Group ≥F3. Results There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble‐CD14 and lipopolysaccharide‐binding protein were significantly higher in both groups vs healthy controls. Baseline soluble‐CD14 correlated with glutamic‐oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic‐pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T‐cell expression was significantly decreased by direct‐acting antiviral treatment. Relapsers (9%) showed higher soluble‐CD14 levels at baseline. Conclusion Surrogate microbial translocation markers and T cell activation are increased in HCV‐infected patients with liver fibrosis and decrease during direct‐acting antiviral treatment.

We evaluated the degree of correlation between the variation of different HIV-1 viral load measures in response to antiretroviral therapy. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for plasma HIV-RNA, and HIV plasma infectivity titration, were performed on prospective samples obtained from 86 antiretroviral-naive patients with symptomatic infection and CD4+ < 300/mm3, enrolled in a randomized double-blind trial of the HIV protease inhibitor saquinavir (SQV) in combination with zidovudine (ZDV). Subjects were stratified according to plasma virus infectivity and examined for correlations between distinct response categories with respect to CD4 count and HIV RNA copy number changes. Infectious virus could be titrated in 72% of patients at baseline. A significant reduction (< 1 log10) in HIV plasma infectivity titer was observed during the study in 69% of these patients. The reduction in plasma infectivity was a good predictor of sustained CD4+ cell increases and of sustained decrease in HIV RNA plasma copies. A decrease of at least 0.5 log10 in HIV RNA copy number was observed in 82% of the treated patients. A good correlation was found between HIV plasma infectivity titer and plasma HIV RNA copy number variations (p < 0.001). However, 10 of 17 patients with unchanged plasma infectivity titer showed a significant reduction in HIV RNA copies. While a good correlation was found between plasma infectivity and RNA plasma copies variations, only a minor correlation was found between CD4+ cell count variation and plasma infectivity titer variation. However, reduction in plasma infectivity was a very good predictor of high CD4 changes.

Hypergammaglobulinemia and anomalies in the IgG subclass distribution are common in HIV-infected individuals and persist even after many years of antiretroviral therapy (ART). The aim of this study was to investigate the IgG profile and dynamics in pregnant HIV-infected Malawian women in the Option B era. Methods: Thirty-seven treatment-naive women received ART from the third trimester of pregnancy to 6 months post delivery (end of the breastfeeding period). ART continuation (group C) or interruption (group I) was then decided on the basis of the CD4+ cell count at enrolment (>350 or 350/ml). Total IgG and IgG subclasses were determined in maternal serum using a nephelometric assay at baseline and at 6 and 24 months postpartum. Results: At enrolment, 36/37 women had IgG levels >15 g/l and there was a predominance of the IgG1 isotype (more than 90%) in parallel with underrepresentation of IgG2 (5.0%). After 6 months of ART, both groups showed a significant median decrease in total IgG (À3.1 g/l in group I, À3.5 g/l in group C) and in IgG1 (À4.0 g/l and À3.6 g/l, respectively), but only a modest recovery in IgG2 levels (+0.16 in group I, +0.14 g/l in group C). At month 24, hypergammaglobulinemia was still present in 73.7% of women in group C, although a significant reduction was observed in total IgG level and in IgG1 and IgG3 subclasses (p < 0.0001 in all cases). IgG2 levels did not show any significant change. In group I at 24 months, total IgG and IgG subclasses had returned to levels comparable to those at baseline. Conclusions: The beneficial effects of 24 months of ART appear to be limited in the B-cell compartment, with an incomplete reduction of total IgG levels and no recovery of IgG2 depletion. A short ART period did not have significant effects on IgG abnormalities in women who interrupted treatment.