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Diet is a modifiable, noninvasive, inexpensive behavior that is crucial in shaping the intestinal microbiome. A microbiome "imbalance" or dysbiosis in inflammatory bowel disease (IBD) is linked to inflammation. Here, we aim to define the impact of specific foods on bacterial species commonly depleted in patients with IBD to better inform dietary treatment. We performed a single-arm, pre-post intervention trial. After a baseline period, a dietary intervention with the IBD-Anti-Inflammatory Diet (IBD-AID) was initiated. We collected stool and blood samples and assessed dietary intake throughout the study. We applied advanced computational approaches to define and model complex interactions between the foods reported and the microbiome. A dense dataset comprising 553 dietary records and 340 stool samples was obtained from 22 participants. Consumption of prebiotics, probiotics, and beneficial foods correlated with increased abundance of Clostridia and Bacteroides , commonly depleted in IBD cohorts. We further show that specific foods categorized as prebiotics or adverse foods are correlated to levels of cytokines in serum (i.e., GM-CSF, IL-6, IL-8, TNF-alpha) that play a central role in IBD pathogenesis. By using robust predictive analytics, this study represents the first steps to detangle diet-microbiome and diet-immune interactions to inform personalized nutrition for patients suffering from dysbiosis-related IBD.

Introduction: Antiretroviral therapy (ART) is the most significant advance in the medical management of HIV-1 infection. Given the fact that HIV cannot be eradicated from the body, ART has to be indefinitely maintained. New approaches need to be defined for monitoring HIV-infected individuals (PLWHIV), including clinical, virologic, immunological parameters and also ways to collect individual points of view and quality of life., Areas Covered: We discuss which tests may be used to improve the management of PLWHIV and respond to a comprehensive health demand., Expert Opinion: Viral load and CD4 counts are well-validated outcome measures and we still need them, but they do not completely depict the health status of PLWHIV. We need to better understand and to apply to clinical practice what happens in sanctuaries, what is the role of HIV DNA, what is the meaning of low-level viremia. Most of these questions do not yet have a definitive response. Further, we need to understand how to modify these variables in order to improve outcomes.Similar points may be raised for immunological measures and for tests exploring the tolerability of drugs. The goal must be the evolution from a viro/immunologic-based to a comprehensive quality-of-health-based evaluation of PLWHIV.

Introduction: Immune activation plays a central pathogenetic role in both HIV-1 replication and depletion of CD4(+) T cells leading to disease progression and the onset of the AIDS. While current antiretroviral therapies suppress viral replication to undetectable levels, they do not normalize the excessive level of T-cell activation and proliferation. A new class of anti-HIV-1 drugs known as antiviral hyperactivation-limiting therapeutics (AV-HALTs) combines direct antiviral activity with an antiproliferative action to limit the hyperactivation of the immune system now recognized as the key driver of the progressive loss of CD4(+) T cells that occurs over the natural course of the HIV-1 infection., Areas Covered: Areas covered include preclinical, Phase I and Phase IIa studies of VS411, the first drug product in a novel class of anti-HIV drugs, AV-HALT agents., Expert Opinion: The two drug combination VS411 safely achieved the goals established for the AV-HALT class based on the results of a Phase IIA proof-of-concept study. Additional work is underway to identify and develop new agents that combine the dual attributes of AV-HALTs, direct reduction of both HIV-1 viral load and markers of excessive immune activation, in a single molecule.

Malaria is a common, life-threatening infection in endemic tropical areas and one that presents a diagnostic challenge to laboratories in most non-endemic countries. A rapid and accurate diagnosis is a prerequisite for effective treatment, especially for the potentially fatal cases of Plasmodium falciparum infection. In the present, multi-centre study, the performances of a rapid diagnostic test (NOW) Malaria) and several, commercial, PCR-based assays (AMS61, AMS42, AMS43, AMS4 and AMS45) were compared against the results of microscopical examination of bloodsmears (the current 'gold standard'). The subjects were either non-European immigrants (N=135) or international travellers (N=171). There was good concordance between the results of all the detection methods, with kappa values of >0.8. Although the NOW Malaria rapid test was both sensitive (100%) and specific (100%) in detecting P. falciparum infections, it was less specific (93.1%) and sensitive (90.7%) in identifying the other Plasmodium species. The results from the AMS61 assay, designed to detect any malarial infection, generally parallelled those of the microscopy (kappa = 0.89), giving a specificity of 98.2% and a sensitivity of 91.0%. Although the use of species-specific molecular primers to identify pure infections with P. falciparum and P. vivax gave results that were in good agreement with those of the microscopy, the subjects who had apparently pure infections with P. ovale or P. malariae were always found PCR-negative. Compared with the standard microscopy, both the NOW Malaria test and the PCR-based assays were therefore poor at identifying mixed infections. The NOW Malaria test and the PCR-based assays clearly need to be improved, particularly for the correct identification of infections with Plasmodium spp. other than P. falciparum, including mixed infections. For now, expert microscopy must remain the mainstay of the laboratory diagnosis of malaria.

In the present study, 67 patients suspected to be cases of visceral leishmaniasis (VL) were each checked for leishmanial infection by the microscopical evaluation of various biological specimens, in-vitro culture, serology and an assay based on nested PCR. Most (35) of the subjects were immunocompetent (IC) but 32 were immunodeficient (ID) as the result of HIV infection (18 cases), treatment to prevent transplanted organs being rejected (six) or haematological malignancies (eight). Forty-one (61.2%) of the subjects (19 IC subjects, 12 HIV-positive patients, four transplant patients and six patients with malignancies) were considered true cases of VL. For the IC subjects, only the production and microscopical examination of leucocytoconcentrates and cultures of Buffy coats gave sensitivities of <80%, the results of the other methods showing higher sensitivities and almost perfect agreement with the 'gold-standard' diagnoses. For the ID subjects, however, only the serological tests and the PCR gave reasonable sensitivities (of >80%). For the initial diagnosis of leishmaniasis in ID patients, IFAT and western blots may be useful, as, among the present ID patients, they gave sensitivities (of 80.9% and 88.2%, respectively) that were almost as high as that for the PCR, and specificities of 100%. In the diagnosis of VL in either IC or ID patients, the assay based on a nested PCR appeared to be particularly reliable, with sensitivities of 88.9% and 95.2%, respectively, and a specificity of 100% in both groups of patients. The testing of bone-marrow aspirates by PCR revealed very few VL cases who were not found positive when samples of their peripheral blood were checked in the same assay. For both IC and ID subjects therefore, the use of the PCR-based method to test samples of peripheral blood (which can be collected much more easily than bone-marrow aspirates and with much less pain for the subject) is recommended.

Purpose: To study whether and under what circumstances HIV can be controlled in chronically infected patients., Method: Nine patients treated with hydroxyurea and didanosine (PANDAs) were compared with 7 patients on highly active antiretroviral therapy (HAART) during an 8-week treatment interruption. Both groups had similar baseline viral load, CD4 count, and length of treatment. Treatment was resumed if viral rebound >10,000 copies/mL (virological failure) or CD4 count decrease below 200 cells/mm(3) (immunological failure) occurred in two consecutive measurements., Results: None of the PANDAs failed. Viral rebound was spontaneously contained, and CD4 count remained stable. Four out of 7 patients in the HAART group failed to control HIV by week 6 and had to restart therapy due to either viremia rebound or CD4 decrease. Before therapy interruption, the PANDAs had a vigorous HIV-specific T cell immune response (median CD4VIR 1.2%), while the HAART-treated patients did not (median CD4VIR 0.2%) (CD4VIR represents the percentage of HIV-specific CD4 subpopulation expressing IFN-gamma within the total CD4 population [CD3+, CD4+, IFN-gamma+]). This difference was statistically significant (p =.002)., Conclusion: This study shows that HIV can be controlled during therapy interruption in patients with established infection, and that control of viral replication correlates with vigorous anti-HIV specific immune responses.

The pharmacokinetics of nelfinavir tablets (A) and an oral simplified nelfinavir suspension (B) were studied. Twelve healthy volunteers randomly received either five 250-mg nelfinavir tablets or a simplified oral suspension obtained from tablets dissolved in water (nelfinavir 1250 mg in 100 mL of water) in a single dose before being crossed over to the second treatment after a one-week washout period. Blood samples were drawn up to 24 h after drug administration. Nelfinavir concentrations in plasma were analyzed by a specific and validated reverse-phase high-performance liquid chromatography assay (HPLC) with UV detection, and pharmacokinetic values were determined. For the AUC(0-infinity) with means+/-SD of 31.71+/-7.85, 30.88+/-10.28 (microg/L) respectively for treatments B and A, the ratio (F(B/A)) was of 1.1 with a C.I. of 0.90-1.24. For Cmax with means+/-SD of 3.1+/-0.6 (treatment B) and 3.2+/-0.8 mg/mL (treatment A), the ratio was 1.0. with C.I. of 0.92-1.08. The two treatments evidenced no significant differences in AUC(0-inifnity) and Cmax values and the two-one sided t-test showed that the two preparations are bioequivalent. There was no significant difference in Tmax between the liquid and tablets. Nelfinavir suspension might be a option for treating HIV-infected patients with swallowing disturbances or compliance problems.

Purpose: To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in naïve patients., Method: This study was a multicenter, open-label, randomized trial in naïve patients with less than 400 CD4+ cell count/microL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viro-immunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations., Results: 262 consecutive patients were enrolled in the study from March 1, 1997 to December 31, 1997, in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75% had viremia below 500 copies/mL, CI = 12.9%, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/microL, SD = 234) when compared to patients enrolled in arm A (57%, CI = 15.5% and 223 CD4+ cells/microL, SD = 192; p =.0353 and.026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 person-years in Arm B; p =.86)., Conclusion: Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in naïve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.