Long-Term Treatment With Raltegravir is Associated with Lower Triglycerides and Platelets Count in the Older HIV+ Population: Results from the Ral-Age Study.

BACKGROUND: Raltegravir (RAL) is considered one of the better-tolerated antiretroviral medications, due to limited side effects and minimal drug-drug interactions. Matherials and Methods: We retrospectively evaluated 96 HIV+, over 60 years old, experienced patients who had switched from any antiretroviral drug to raltegravir-based nuc-sparing or standard nucleoside-backbone regimens. A control group with patients aged under 60 years old was included. RESULTS: The median age of the patients was 66 years (IQR 10.5) (77 M, 19 F); the median time horizon of follow-up was 4 years (IQR 5). HIV-RNA at baseline was undetectable for more than 6 months in most of the patients. Median CD4+ count was 453 cells/mmc (IQR 379). 49 patients had AIDS history. All the patients were assuming concomitant medications. No adverse effect attributed to the use of raltegravir was reported in the medical records. Only 2 patients presented virological failure, whereas viremic blips were observed in 10 patients. After switching to RAL-containing regimens triglycerides values showed a statistically significant reduction from a median value of 172 (IQR 105.5) mg/dl to 129 mg/dl (IQR 73) (p=0,0001). Switching to a standard regimens was associated with a marked reduction of triglycerides. Cholesterol levels were reduced at the time of follow-up (T2) but no significant modifications were observed when patients which had introduced drugs to treat dislypidemia were removed from the analysis; in contrast, triglycerides reduction was also confirmed in this sub-group. Patients presented higher levels of CD4+ at T2 and reduced platelet count [from 230 300/mmc (SD 123 527) to 197 125/mmc (SD 66 377), p=0,04]. Similar trends were observed in younger patients. CONCLUSION: RAL-containing regimens are safe and highly effective in the older population. RALtreatment is associated with the reduction of triglycerides and platelets count in the older population.

An oral high dose of cholecalciferol restores vitamin D status in deficient postmenopausal HIV-1-infected women independently of protease inhibitors therapy: a pilot study.

The best repletion and maintenance dosing regimens with cholecalciferol in vitamin D-deficient HIV-1 patients remain unknown. Protease inhibitors (PIs) have been shown to inhibit vitamin D 1α- and 25α-hydroxylation in hepatocyte and monocyte cultures. We therefore evaluated the effect of a single high dose of cholecalciferol in vitamin D-deficient HIV-1 postmenopausal women undergoing treatment with highly active anti-retroviral therapy (cART), with and without PIs. Forty HIV-1 postmenopausal women treated with cART, with hypovitaminosis D (<20 ng/ml), were enrolled. We measured serum changes of 25-hydroxyvitamin D [25(OH)D]; 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), serum calcium, and urinary calcium excretion following a loading dose of 600,000 IU of cholecalciferol after 3, 30, 60, 90, and 120 days. Patients were divided into two groups, whether or not they were taking PI. A significant increase in mean 25(OH)D and 1,25(OH)2D levels at day 3 and throughout the entire observation period was found in both groups (p < 0.001). PTH levels concomitantly decreased in both groups (p < 0.001). Mean albumin-adjusted serum calcium increases with respect to baseline were significant only at day 3 and day 30 for both groups (p < 0.01). Considering remaining parameters, there were no significant differences between the groups at any time, by two-way RM ANOVA. An oral dose of 600,000 IU of cholecalciferol in HIV-1 postmenopausal women rapidly increases 25(OH)D and 1,25(OH)2D levels reducing PTH levels, regardless of the presence of PIs in the cART scheme.

Levofloxacin and Tobramycin for Severe Bacterial Keratouveitis.

PURPOSE: To report on clinical features and outcome of severe bacterial keratouveitis. METHODS: Twenty patients with severe bacterial keratouveitis treated with topical tobramycin and levofloxacin and oral levofloxacin were included. Main outcome measures were ulcers location, bacterial isolates, risk factors, visual prognosis. RESULTS: Centrally located ulcer/abscess was present in 65% of patients. Contact lens (CL) wear was the most common risk factor (70%). Bacterial isolates were observed in 58% of patients, none resistant to tobramycin and levofloxacin. Pseudomonas aeruginosa was found in 47% of positive cases and in 64% of CL wearers. After therapy, the mean visual acuity improved significantly (p < 0.0001), particularly in contact lens wearers (p = 0.04) and in patients younger than 60 years old (p < 0.001). CONCLUSIONS: Pseudomonas aeruginosa is the most frequent cause of bacterial keratouveitis and CL wear the most common risk factor. Topical tobramycin and levofloxacin and oral levofloxacin are effective in the treatment of bacterial keratouveitis.

Long-term IFN-γ and IL-2 response for detection of latent tuberculosis infection in healthcare workers with discordant immunologic results.

Discordant results between the interferon-gamma release assays (IGRAs) and tuberculin skin test (TST) are common in latent tuberculosis infection (LTBI). We evaluated whether the measurement of IFN-γ and interleukin (IL)-2T-cell responses, after prolonged Mycobacterium tuberculosis-specific antigen stimulation, can be used as adjunctive biomarker for LTBI detection in subjects with discordant results between TST and QuantiFERON-Gold In-Tube (QFT). 196 healthcare workers were screened for LTBI and in 90 of those participants, the QFT was repeated after 18 h, and IFN-γ/IL-2 immune response was measured after 72 h long-term stimulation. Of the 196 patients, 34 had positive, 155 negative, and 7 indeterminate QFT results. Discordant TST+/QFT- results were found in 29 (14.7%) patients, of whom 6 (20.6%) were Bacillus Calmette-Guerin (BCG) vaccinated. None of 23 non-BCG vaccinated subjects showed a specific IFN-γ immune response after 18 h nor 72 h of incubation, whereas 3/23 (13.04%) discordant subjects produced a specific long-term IL-2 response, which might reflect a LTBI status. In LTBI group (TST+/QFT+) both cytokine levels were increased after long-term in comparison to short-term stimulation. No significant long-term IFN-γ/IL-2 secretion was detected in control group (TST-/QFT-). Taken together, our data showed that the 87% of discordant patients who did not respond to the long-term assay, as controls subjects, were judged LTBI negative. The use of classic QFT and long-term IL-2 response may have a potential role to clarify the LTBI status in individuals in whom the diagnosis of LTBI is uncertain due to the discordance of the available diagnostic tests, such as TST and IGRA.

Interferon-γ release assay in HIV-infected patients with active tuberculosis: impact of antituberculous drugs on host immune response.

The objective of the study was to: 1) investigate the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) in HIV-infected patients with active tuberculosis (TB); 2) evaluate the sequential changes in QFT-GIT assay during the treatment response; 3) investigate the direct in vitro effects of antituberculous drugs on both secretion of IFN-g and apoptosis of T cells. Forty-four HIV-patients with active TB were enrolled and tested with QFT-GIT. Thirteen of them were followed longitudinally by QFT-GIT, performed at baseline and six and nine months after TB-treatment onset. For in vitro experiments, cells from healthy donors and HIV-naive subjects were pretreated with four antituberculous-drugs, and then examined for IFN-g secretion and apoptosis of T-cells. The QFT-GIT was positive in 66%, negative in 11.3% and indeterminate in 22.7%. Longitudinal analysis in 13 HIV-TB subjects showed that at therapy completion a reversion to negative response was found only in 38.4% of patients, but in 30.7% the QFT-GIT remained positive. Overall, during the anti-TB treatment no significant decrease in average IFN-g response was observed in these patients (p<0.001). In vitro experiments showed that the four antituberculous- drugs, within the range of therapeutically achievable concentrations, did not exert any down-regulatory effect on IFN-g production and did not have any effect on apoptosis of T cells from HIV naïve subjects. Despite the high rate of indeterminate results, QFT-GIT assay may represent a good tool in the diagnostic workup for active TB in HIV-patients. Although the antituberculous drugs do not have any direct effect on host immune response to mycobacterial antigen, changes in longitudinal IGRA response have been found during in vivo anti-TB treatment.

The combination of FRAX and Ageing Male Symptoms scale better identifies treated HIV males at risk for major fracture.

OBJECTIVE: Osteoporosis and hypogonadism are common in men with HIV infection. Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX provides 10-year probability of major fractures. We investigated the role of AMS scale combined with FRAX without bone mineral density (BMD), in identifying HIV men with bone fragility. DESIGN: Cross-sectional observational study. METHODS: Fifty HIV-positive men treated with highly active antiretroviral therapy and 27 controls underwent hormonal evaluation, BMD scan and spine X-ray. The AMS questionnaire was administered. RESULTS: Osteoporosis was found in 24·0% of HIV patients and in 3·7% of controls (P = 0·05). In HIV patients, 9 radiological vertebral fractures were found (none in controls, P = 0·04). Calculated free testosterone suggested hypogonadism in 26% of HIV patients vs 4% of controls (P = 0·04); an abnormal AMS score (≥27) was found in 62% HIV patients compared with 41% controls (P = 0·04). ROC curves showed that FRAX for major fracture had a 23% sensitivity and a 100% specificity in identifying HIV patients with bone fragility (P = 0·002, with the threshold of 7% at which bisphosphonate therapy is cost-effective). Considering a value of AMS ≥27, we obtained an 82·6% sensitivity and a 42·9% specificity (P = 0·04). The combination of AMS and FRAX score achieved a 77·3% sensitivity and a 69% specificity (P = 0·02, cut-off 34). CONCLUSION: Combination of FRAX (without BMD) and AMS improved sensitivity of FRAX alone in identifying HIV patients at fracture risk, at the expense of reduced specificity.