Long-term Use of Proton Pump Inhibitors Is Associated With Increased Microbial Product Translocation, Innate Immune Activation, and Reduced Immunologic Recovery in Patients With Chronic Human Immunodeficiency Virus-1 Infection.

BACKGROUND: Translocation of microbial products from the damaged gut causes increased immune activation in human immunodeficiency virus (HIV). Proton pump inhibitors (PPIs) predispose to bacterial overgrowth in the gut. We hypothesized that long-term use of PPIs is associated with greater microbial translocation and immune activation in HIV. METHODS: HIV-infected persons on suppressive antiretroviral therapy (ART), including those receiving long-term PPIs (PPI+ group) or not (PPI- group), were enrolled. We determined CD38+HLA-DR+CD8+ (activated) T-cell frequency, and plasma levels of lipopolysaccharide (LPS), LPS binding protein (LBP), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP). RESULTS: We recruited 77 HIV-infected participants (37 PPI+ and 40 PPI-) and 20 HIV-uninfected volunteers. PPI+ subjects were older and more likely to have hypertension and receive statins than PPI-. Nadir and enrollment CD4 counts, activated T-cells, and time on ART were similar in both groups. PPI+ group had higher sCD14 (2.15 vs. 1.50 mcg/mL, P < .01), and LBP (21.78 vs. 18.28 mcg/mL, P = .02) but lower I-FABP levels (608.5 vs. 2281.7 pg/mL, P = .05) than PPI-. In multivariate analysis, sCD14 levels remained associated with PPIs. In the year prior to enrollment, PPI+ group lost more CD4 cells than PPI- (-18 vs. 54 cells/mm3, P = .03). HIV-infected subjects had higher immune activation and microbial translocation biomarkers than uninfected volunteers. CONCLUSION: In HIV, long-term use of PPIs was associated with increased microbial translocation, innate immune activation, and reduced immune reconstitution. Further studies are needed to evaluate the clinical implications of our findings. In the meantime, cautious use of PPIs is advised.

Relationship between osteopenia, free testosterone, and vitamin D metabolite levels in HIV-infected patients with and without highly active antiretroviral therapy.

The prevalence of osteopenia in HIV-infected patients is high. However, the mechanisms implicated in bone mass loss in HIV infection are unclear. Because of this, we analyzed serum free testosterone and vitamin D3 hydroxylated metabolites in HIV-infected patients, with and without antiretroviral treatment, and the relation between them and osteopenia. Seventy-four HIV-infected patients were selected because they had frozen sera available at a date close to a DEXA evaluation. Free testosterone, 25(OH)D3, and 1,25(OH)2D3 were determined in frozen serum. There were no differences in free testosterone, 25(OH)D3, and 1,25(OH)2D3 levels between patients with and without osteopenia. 25(OH)D3 levels in naive and HAART-treated patients were 26.2 (10.3-32.8) and 33.1 (20.6-46.8) ng/ml, respectively (p = 0.04). 1,25(OH)2D3 levels in naive and HAART treated patients were 60.3 (49.2-80.8) and 85.5 (68-111.6) pmol/liter (p = 0.01). Free testosterone levels in 9 naive men and in 50 HAART-treated men were 42.6 (24.1-67.3) and 69.2 (47.5-112.1) pmol/liter, respectively (p = 0.04). In conclusion, HIV-infected patients with and without osteopenia showed similar levels of vitamin D metabolites and free testosterone. However, antiretroviral drug-naive patients showed lower serum levels of vitamin D metabolites and free testosterone than HAART-treated patients.

[Anti-ulcer drug consumption in Spain]. / Consumo de fármacos antiulcerosos en España.

OBJECTIVE: To check whether therapy to eradicate Helicobacter pylori has succeeded in reducing the consumption of traditional ulcer medication. DESIGN: A longitudinal, retrospective study of the use of medication. SETTING: Spain in the decade from 1988 to 1997. PARTICIPANTS: Pharmaceutical products belonging to the anatomical therapeutic group AO2B (for ulcers) and dispensed at the Social Security's expense. MEASUREMENTS AND MAIN RESULTS: Despite the widespread use of treatments to eradicate H. pylori, it was found that consumption of ulcer medication continued to increase markedly, from 5 daily doses per 1000 inhabitants in 1988 to 19 in 1997. In 1997 the two most frequently taken active principles in the group were omeprazole and ranitidine. Drugs indicated for gastric protection were also used much more. However, in absolute values, they stayed well below anti-H2 drugs and proton pump inhibitors. CONCLUSION: The introduction into Spain of therapy to eradicate H. pylori has failed to reduce the use of ulcer medication. The use of anti-H2 drugs and proton pump inhibitors for gastric protection may explain a part of the increase in consumption experienced by these two pharmacological groups.

[Changes in the pattern of opioid analgesic consumption in Spain]. / Cambios en el patrón de consumo de analgésicos opioides en España.

BACKGROUND: Data from different sources have proved an infrautilization of opioid analgesics in Spain. A descriptive study has been conducted in order to know the utilization of these drugs and changes in the pattern of use in the last few years. MATERIAL AND METHOD: To know the consume of narcotic analgesic drugs, N02A group of the Anatomic Therapeutic Classification, a search was developed in the ECOM database from the Spanish Ministry of Health. This database contains information of drug preparations prescribed throughout the National Health Care System. RESULTS: The consumption of opioid analgesics in Spain has been multiplied by 5.2 during this period. It has increased from 94.7 defined daily dose per 1,000,000 inhabitants in 1985 to 489.4 in 1994. The most consumed drug in 1994 was dihydrocodeine, followed by tramadol. The number of defined daily dose per inhabitant and day of parenteral administration have decreased during the last years. CONCLUSIONS: Availability of new analgesic opioid drugs with better pharmacokinetic profiles has contributed to an increase of their consume in Spain.