Unconventional T cells in chronic hepatitis B patients on long-term suppressive therapy with tenofovir followed by a Peg-IFN add-on strategy: A randomized study.

HBV eradication in chronic hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg-IFN), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long-term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg-IFN-α-2a add-on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsAg occurred in the add-on group compared with the NA group at W12 (P = .016) and at W24 (P = .012). A decline of qHBsAg ≥0.5 log10 at week 24 occurred in 4 of 10 patients in the add-on arm and 1 of 20 in the NA arm, respectively (P = .03). HBsAg loss was seen in 20% of subjects in the add-on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT (P = .03) and γδ T cells (P = .03) as well as fewer γδ T cells expressing Vδ2 T-cell receptors (P = .005). No changes in unconventional T-cell frequency and function were shown in both add-on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB. Despite a greater qHBsAg decline of add-on patients, our data failed to detect any effect of Peg-IFN treatment on unconventional T cells.

Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial.

Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4(+) T-cell depletion, deterioration of gut lining, and fecal microbiota composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active antiretroviral therapy (HAART)-naive HIV-1-infected adults. In a pilot double-blind, randomized, placebo-controlled study, 57 HAART-naive HIV-1-infected patients received a unique oligosaccharide mixture (15 or 30 g short chain galactooligosaccharides/long chain fructooligosaccharides/pectin hydrolysate-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) daily) or a placebo for 12 weeks. Microbiota composition improved significantly with increased bifidobacteria, decreased Clostridium coccoides/Eubacterium rectale cluster, and decreased pathogenic Clostridium lituseburense/Clostridium histolyticum group levels upon prebiotic supplementation. In addition, a reduction of soluble CD14 (sCD14), activated CD4(+)/CD25(+) T cells, and significantly increased natural killer (NK) cell activity when compared with control group were seen in the treatment group. The results of this pilot trial highly significantly show that dietary supplementation with a prebiotic oligosaccharide mixture results in improvement of the gut microbiota composition, reduction of sCD14, CD4(+) T-cell activation (CD25), and improved NK cell activity in HAART-naive HIV-infected individuals.

Immunological mechanisms of interleukin-2 (IL-2) treatment in HIV/AIDS disease.

HIV establishes a chronic infection that is marked by the progressive depletion of CD4+ T-cells, yet the mechanisms by which this depletion arises are a matter of controversy. Evidence is accumulating that T CD4+ depletion is not effected solely by virus-mediated killing and that mechanisms involving T-cell dynamics play a major role in the pathogenesis of HIV infection. Hence antiretroviral therapy, by controlling viral replication alone, invariably fails to achieve the broadest immune reconstitution. This issue has strengthened the rationale to widely explore new adjuvant immunotherapy. Most work has been performed on IL-2, given its potential to correct HIV-driven immune defects, possibly translating in a more effective immune competency. Important insights stem from the IL-2-mediated immune reconstitution pattern, with a rise in peripheral turnover and thymopoiesis, IL-7 synthesis and functional markers, resulting in the correction of the skewed T-cell immunophenotype and cytokine milieu. Combined, these findings suggest that IL-2 has a beneficial effect in correcting the severe disruption in T-cell homeostasis induced by HIV, through the interaction with T-cells and cytokine microenvironment. However, whether or not these immunologic effects translate in an actual immunologic competency and therefore clinical benefit, still awaits demonstration from ongoing large, controlled clinical studies.

Recent acquired STD and the use of HAART in the Italian Cohort of Naive for Antiretrovirals (I.Co.N.A): analysis of the incidence of newly acquired hepatitis B infection and syphilis.

OBJECTIVE: To estimate the incidence of newly acquired syphilis (n-syphilis) and hepatitis B infection (n-hepatitis B) in I.Co.N.A. and to evaluate the impact of HAART, calendar date and risk group. METHODS: Cohort study: Incidence was calculated by person-years analyses. Poisson regression was used for the multivariate model. RESULTS: The rate of n-syphilis was 23.4/1,000 PYFU and it increased over time; HIV transmission risk was the most important predictor: men who have sex with men (MSM) had a considerable higher risk (RR 5.92, 95% CI 2.95-12.13 vs IDU/exIDU, p<0.0001). The rate of n-hepatitis B was 12.2/1,000 PYFU; it declined in recent years and halved per 10 years age. Patients with HIV-RNA<500 copies/ml had a 60% reduced risk of n-hepatitis B if they were treated with HAART compared with not treated individuals. CONCLUSIONS: In our population, the use of HAART was not associated with a higher risk of newly acquired sexually transmitted diseases (STD). Suppressive HAART was associated with a lower risk of HbsAg seroconversion. Incidence of n-hepatitis B has recently been declining possibly due to herd immunity provided by vaccination policies. The risk of acquiring n-syphilis has increased over time and it is higher in the population of MSM compared with other categories of HIV exposure.