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Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.

ABSTRACT: People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown.DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults.This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults.The study was conducted at an academic medical center.Twenty nondiabetic HIV-positive men and women (9.8 ± 5.5 years of known HIV) taking antiretroviral therapy and with stable immune (625 ± 134 CD4+ T cells per microliter) and virological (<48 copies HIV RNA per milliliter) status.The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks.CD4+ T cell number and plasma HIV RNA were measured every 4 weeks; fasting serum regulated upon activation normal T-cell expressed and secreted (RANTES), stromal derived factor (SDF)-1?, Soluble TNF receptor II, and oral glucose tolerance were measured at baseline, week 8, and the end of study. ANOVA was used for between-group comparisons; P < .05 was considered significant.Compared with placebo, sitagliptin did not reduce CD4+ T cell count, plasma HIV RNA remained less than 48 copies/mL, RANTES and soluble TNF receptor II concentrations did not increase. SDF1? concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8.Despite lowering SDF1? levels, sitagliptin did not adversely affect immune or virological status, or increase immune activation, but did improve glycemia in healthy, nondiabetic HIV-positive adults. These safety data allow future efficacy studies of sitagliptin in HIV-positive people with cardiometabolic complications.

SUBMITTER: Goodwin SR

PROVIDER: S-EPMC3565112 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.

Goodwin Scott R SR Reeds Dominic N DN Royal Michael M Struthers Heidi H Laciny Erin E Yarasheski Kevin E KE

The Journal of clinical endocrinology and metabolism 20121221 2

<h4>Context</h4>People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown.<h4>Objective</h4>DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive ad ...[more]

PMID: 23264399

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Project description:Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor-associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor-associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor-associated angioedema and 176 angiotensin-converting enzyme inhibitor-exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg(9)-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6+/-7.8 versus 29.6+/-7.3 nmol/mL per minute; P=0.026) and antigen (465.8+/-260.8 versus 563.1+/-208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor-associated angioedema compared with angiotensin-converting enzyme inhibitor-exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5+/-4.9 versus 29.8+/-6.7 nmol/mL per minute; P=0.001) and antigen (354.4+/-124.7 versus 559.8+/-163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.

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Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.

Publications

Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.

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