didanosine and Hyperglycemia

The combination of didanosine (ddI) and tenofovir (TDF) has potential advantages, but because of several pitfalls (unexpected decreases in CD4+ T cells, increased risk of pancreatitis) its use has been questioned. Since anecdotal cases of transient insulin-dependent diabetes mellitus were seen in our clinic in patients on ddI + TDF-containing regimens, we explored the rate of this complication in more detail. Retrospective analysis of plasma glucose levels in patients who completed 12 months of treatment with three different triple antiretroviral regimens including ddI + TDF, TDF, or ddI was done. Patients taking antidiabetic drugs and/or those with baseline glucose levels >125 mg/dl were excluded. Weight, age, concomitant antiretrovirals, and ddI dose were assessed. At 12 months without treatment changes, fasting glucose levels were compared to baseline. A multivariate analysis was performed to evaluate which variables were associated with glucose elevations. A total of 177 HIV-infected patients were assessed (78 on ddI + TDF, 42 on TDF, and 57 on ddI). Mean baseline features were well balanced between groups for age (mean, 39 years), gender (78% male), CD4+ count (mean, 507 cells/mm3), weight (mean, 67 kg), and glucose level (mean, 95 mg/dl). There were only significant differences between groups for baseline viral load and protease inhibitor (PI) use (13% in the ddI + TDF arm vs. 7% and 9% in the TDF and ddI arms, respectively). At 12 months, 60% of the patients in the ddI + TDF arm were taking ddI 250 mg/day and the rest were on ddI 400 mg/day. At 12 months, hyperglycemia was significantly more frequent in the ddI + TDF arm (33%) when compared to patients on TDF or ddI separately (5% and 10%, respectively). In the multiple linear regression analysis, a lower weight (beta -0.35; 95% CI -0.67 to -0.03; p = 0.033) and use of ddI + TDF (beta: 13.05; 95% CI: 0.2 to 26; p = 0.047) were independently associated with a higher risk of developing hyperglycemia. The risk of hyperglycemia is increased in patients treated with ddI + TDF, particularly in those with lower weight. As high ddI exposure has been associated with endocrine pancreatic dysfunction and diabetes, ddI "overdosing" as result of concomitant TDF use and low weight might explain our findings. These results add a further note of caution to the use of TDF and ddI in combination.

Topics: Adenine; Adult; Anti-HIV Agents; Blood Glucose; Didanosine; Drug Therapy, Combination; Fasting; Female; Follow-Up Studies; HIV Infections; Humans; Hyperglycemia; Linear Models; Male; Organophosphonates; Retrospective Studies; Risk Factors; RNA, Viral; Tenofovir; Time Factors; Treatment Outcome; Virus Replication

We determined the frequency and clinical nature of severe hyperglycemia in a university clinic for HIV-1-infected patients. The medical records of 1392 adult HIV-infected patients were reviewed for cases of severe hyperglycemia, defined as two or more serum glucose values >250 mg/dl or diabetes treatment during clinic care. Demographic information, family histories of diabetes mellitus, body weights, CD4+ lymphocyte counts, and use of corticosteroids, megestrol acetate, pentamidine, or didanosine were recorded for subjects meeting the case definition. Comparisons were made between preexisting diabetic (group 1) and incident hyperglycemic cases (group 2). Less than 2% of the total clinic population experienced severe hyperglycemia: 12 in group 1 and 13 in group 2. Group 2 had lower body weights (mean, 70.6 kg versus 90.0 kg; p < 0.05) and more advanced HIV disease (mean CD4 count, 79/mm3 versus 550/mm3; p < 0.05) than group 1. Group 2 cases had evidence of drug-associated hyperglycemia; four cases demonstrated hyperglycemia coinciding with large fluctuations in weight during megestrol therapy. Among megestrol recipients, cases did not differ from noncases in demographics, weight, or CD4 count. Severe hyperglycemia is uncommon in adult HIV-infected patients. Approximately one half of these patients have preexisting diabetic conditions; many of the remainder may have drug-induced hyperglycemia, especially as a result of corticosteroids or megestrol acetate.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-HIV Agents; Diabetes Complications; Diabetes Mellitus; Didanosine; Female; HIV Infections; Humans; Hyperglycemia; Male; Megestrol Acetate; Middle Aged; Pentamidine; Retrospective Studies

To determine whether didanosine (DDI), one of the drugs commonly used to treat infection with human immunodeficiency virus (HIV), contributes to the development of diabetes and hyperosmolar nonketotic diabetic syndrome (HNKDS).. One female patient was treated with DDI for infection with HIV during pregnancy. Soon after starting DDI treatment, she developed diabetes, which progressed to HNKDS.. Although not reported in the literature, hyperglycemia following treatment with DDI has been noted in 82 patients and is usually associated with pancreatitis. DDI should be recognized as one of the drugs known to potentially cause diabetes and HNKDS. With the increasing use of DDI and other drugs that cause hyperglycemia, such as pentamidine and dapsone, blood glucose should be monitored frequently in the HIV-infected patients.

Topics: Adult; Blood Glucose; Didanosine; Female; HIV Infections; HIV Seropositivity; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Monitoring, Physiologic; Pregnancy; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; Didanosine; Female; Humans; Hyperglycemia; Pancreatitis