Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.
J Clin Endocrinol Metab
; 98(2): 743-51, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23264399
ABSTRACT
CONTEXT 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. OBJECTIVE:
DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults.DESIGN:
This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults.SETTING:
The study was conducted at an academic medical center.PARTICIPANTS:
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. INTERVENTION The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks. MAIN OUTCOMEMEASURES:
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)-1α, 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.RESULTS:
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. SDF1α concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8.CONCLUSIONS:
Despite lowering SDF1α 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazinas
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Triazóis
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Linfócitos T CD4-Positivos
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Infecções por HIV
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Soropositividade para HIV
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Inibidores da Dipeptidil Peptidase IV
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article