Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women.
ABSTRACT To assess the association between protease inhibitor (PI) use and the incidence of diabetes mellitus (DM) among participants in the Women's Interagency HIV Study.
Prospective multicenter cohort study. The diagnosis of DM was based on self-report at semiannual interviews conducted from 1994 to 1998.
Six inner-city clinical sites in the United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San Francisco, CA; and Los Angeles, CA).
A total of 1785 nonpregnant women who had no history of prior DM. The women made up four groups: 1) PI users (n = 609, person-years [PY] at risk = 707); 2) reverse transcriptase inhibitor (RTI)-only users (n = 932, PY = 1486); 3) HIV-infected women reporting no antiretroviral therapy (ART) ever (n = 816, PY = 1480); and 4) HIV-uninfected women (n = 350, PY = 905).
Incidence of DM and median body mass index (BMI) from 1995 to 1998 were compared among the four groups.
Sixty-nine incident cases of DM occurred among 1785 women (1.5 cases per 100 PY; 95% CI: 1.2-1.9). The incidence of DM among PI users was 2.8 cases per 100 PY (2.8%) versus 1.2% among both RTI users and women on no ART (95% CI: 1.6-4.1 [PI]; 0.7-1.8 [RTI and no ART]; P = 0.01 for comparison of the PI group with the RTI group) and 1.4% among HIV-uninfected women (95% CI: 0.7-2.2, P = 0.06 for comparison with PI group). Weight gain was not associated with either PI or RTI use. Multivariate models identified PI use (hazard ratio [HR] = 2.90 [95% CI: 1.50-5.60]; P = 0.002), age (HR = 1.75 per 10 years [95% CI: 1.31-2.34]; P = 0.0002) and BMI as independent risk factors for DM.
PI use was associated with a threefold increase in the risk of reporting incident DM. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is advisable.
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ABSTRACT: Although human immunodeficiency virus (HIV)-related morbidity and mortality rates in patients with advanced HIV infection who are treated with combination antiretroviral drugs have declined, significant metabolic adverse effects associated with these regimens have been increasingly recognized. However, since data from patients studied before and after initiation of protease inhibitor (PI) therapy are scant, the true effect of PIs on these metabolic changes remains unknown. To examine temporal trends in serum glucose and lipid levels after initiation of PI therapy, to assess whether changes are independent of virological response and improvement in disease severity, and to determine risk factors associated with the development of hyperglycemia, hyperlipidemia, and lipodystrophy. A 5-year historical cohort analysis in a population of 221 HIV-infected patients observed in the Infectious Diseases Clinic of a tertiary care center from October 1, 1993, through July 31, 1998. Clinical and laboratory data were retrieved from medical records and a computerized database. The main outcome measure was the incidence of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy. Adjusted incidence rate ratios (IRRs) were estimated by means of Poisson regression. In addition, mixed regression analyses were performed to examine effects of PIs on serum lipid and glucose levels, modeled as continuous outcomes. The cumulative incidence of new-onset hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy was 5%, 24%, 19%, and 13%, respectively. Most of these events occurred after initiation of PI therapy. Protease inhibitors were independently associated with hyperglycemia (adjusted IRR, 5.0; 95% confidence interval [CI], 1. 3-19.4), hypercholesterolemia (adjusted IRR, 2.8; 95% CI, 1.5-5.2), hypertriglyceridemia (adjusted IRR, 6.1; 95% CI, 3.1-11.7), and lipodystrophy (adjusted IRR, 5.1; 95% CI, 1.9-13.9). Anabolic steroids and psychotropic medications were also associated with lipodystrophy. Inclusion of potential intermediate variables (eg, virological suppression and increase in body weight) did not reduce the magnitude of the association with PIs. The association between hypertriglyceridemia and ritonavir was stronger than for other PIs (Wald test, P=.02). In contrast, the incidence of hyperglycemia, hypercholesterolemia, and lipodystrophy did not vary significantly across different PIs. Longitudinal mixed models confirmed that serum lipid levels were more substantially affected by antiretroviral therapy, particularly PIs, than serum glucose levels. Similarly, controlling for surrogate markers did not abolish the strong association between PIs and increase in serum lipid levels. We found an independent association between PI use and hyperglycemia, hyperlipidemia, and lipodystrophy that is not explained by the antiviral and therapeutic effect of PIs.Archives of Internal Medicine 08/2000; 160(13):2050-6. · 11.46 Impact Factor
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ABSTRACT: Weight loss and wasting are significant complications of HIV disease. HIV protease inhibitor therapy promotes clinical, immunologic and virologic improvement in HIV-infected patients. In this study, we sought to determine the specific effect of HIV protease inhibitors on patient weight. Ten consecutive HIV patients were treated with protease inhibitor-containing regimens over six months. CD4 T-cell counts, plasma viral load levels and bariatric changes were monitored during the study. Patients experienced a mean weight gain of 19 Pounds (P = 0.006). There was a significant increase in mean CD4 T-cell count (P = 0.008) and a significant decrease in mean viral load level (P = 0.004). The increase in CD4 T cells did not correlate with weight gain, whereas the decrease in viral load did show a significant correlation with the weight increase (P = 0.003). The mechanism of protease inhibitor-induced weight gain is discussed. The medications may also be useful for wasting diseases unrelated to HIV.Research in Virology 01/1998; 149(2):123-6.
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ABSTRACT: Characteristics, prevalence, and risk factors for non-insulin-dependent diabetes mellitus (NIDDM) among Hispanics, blacks, and whites aged 20-74 yr in the United States population were investigated with two national surveys that used a household interview to ascertain diagnosed diabetes and a 75-g 2-h oral glucose tolerance test to measure undiagnosed diabetes. The Hispanic Health and Nutrition Examination Survey of 1982-1984 studied Mexican Americans in the southwest U.S., Cuban Americans in the Miami, Florida, area, and Puerto Ricans in the New York City area. The National Health and Nutrition Examination Survey of 1976-1980 examined a national sample of U.S. residents, of whom data on blacks and whites were analyzed. People with diagnosed diabetes in the five populations were similar with respect to mean age (53-57 yr), age at diagnosis (45-48 yr), duration of diabetes (6.9-8.7 yr), and diabetes therapies (58-67% using pharmacological treatment). Mean age of people with undiagnosed diabetes (51-59 yr) was comparable to that of diagnosed cases, and mean fasting (7.1-7.8 mM) and 2-h postchallenge plasma glucose (14.1-15.5 mM) values for people with undiagnosed diabetes were similar among the five populations. However, obesity levels varied by race, sex, and whether diabetes was diagnosed or undiagnosed. Age-standardized prevalence of diabetes (sum of diagnosed and undiagnosed cases) was 6.2% in whites, 9.3% in Cubans, 10.2% in blacks, 13% in Mexican Americans, and 13.4% in Puerto Ricans. Thus, compared to whites, diabetes rates were 50-60% higher among Cubans and blacks and 110-120% higher among Mexican Americans and Puerto Ricans. Age-standardized rates of impaired glucose tolerance were similar among the five populations (10.3-13.8%). Increasing age, obesity, and family history of diabetes were associated with higher rates of diabetes but sex, physical activity, education, income, and acculturation were not risk factors or were only weakly associated with diabetes prevalence.Diabetes Care 08/1991; 14(7):639-48. · 7.74 Impact Factor