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Protease Inhibitor Use and the Incidence of Diabetes Mellitus in a Large Cohort of HIV-Infected Women

April 24, 2003

This article is part of The Body PRO's archive. Because it contains information that may no longer be accurate, this article should only be considered a historical document.

Newly diagnosed diabetes mellitus (DM), exacerbations of preexisting DM, hyperlipidemia, and fat redistribution syndromes have been described among protease inhibitor (PI) users. In the current study, researchers examined the incidence of self-reported DM among participants of the prospective multicenter Women's Interagency HIV Study from 1994-1998, a period spanning PI introduction. The study assessed the epidemiologic relationships among diabetes, weight change, stage of illness, virologic response to therapy, and the use of specific antiretroviral medications among participants with no prior history of DM.

The HIV-infected and uninfected women (n= 1,435 and 350, respectively) were similar in median age (37 years vs. 36 years), race/ethnicity (55 percent vs. 52 percent African American, 26 percent vs. 30 percent Latina), and median follow-up time (2.91 years). The HIV-positive women had a lower baseline median body mass index than uninfected women (25.5 kg/m2 vs. 26.4kg/m2) and were less likely to be obese, defined as BMI greater than 30kg/m2 (23 percent vs. 33 percent). Among HIV-positive women, 27 percent had baseline CD4 counts below 200 cells/microliter and 34 percent had HIV RNA levels below 4,000 copies/mL. Median detectable baseline HIV RNA was 4.75 log10.

HIV-infected women were divided into three groups. PI users reported at least one PI, at least one nucleoside reverse transcriptase inhibitor (NRTI), and/or at least one nonnucleoside reverse transcriptase inhibitor (NNRTI). Reverse transcriptase inhibitor (RTI) users reported at least one NRTI and/or at least one NNRTI but never reported use of any PI. Women in the No ART group never reported using any PI, NRTI, or NNRTI.

There were 69 new cases of self-reported DM among 1,785 women who contributed 4,578 person-years (PY), an overall incidence of 1.5 per 100 PY. Per 100 PY, DM incidence was 1.4 among the HIV-uninfected women and 1.2, 1.2, and 2.8 in the RTI, No ART, and PI groups, respectively. The relative risk (RR) of reporting DM was highest among the morbidly obese (RR= 5.2) and the obese (RR= 2.8). Adjusted for BMI, women on PI therapy had a greater risk of reporting DM than women on RTI therapy (RR=2.2).

Incident DM and first PI use were reported at the same study visit for 9 of 20 (45 percent) of the diabetic participants in the PI group. The remaining participants reported incident DM one (n= 3), two (n= 6), or three (n= 2) study visits after the first report of PI use. PI therapy was used continuously in 15 of the 20 diabetic participants. In the remaining five, PI use and incident DM were reported at the same visit, despite earlier interruptions in PI therapy.

Virologic response to therapy was determined for 86 percent of the RTI and PI groups. In the RTI group, virologic response occurred in 25 percent of diabetic participants and 28 percent of nondiabetic participants. In the PI group, virologic response occurred in 53 percent of diabetic participants and 52 percent of nondiabetic participants.

Frequency of zidovudine (AZT), stavudine (d4T), zalcitabine (ddC), didanosine (ddI), or lamivudine (3TC) use was the same for both diabetic and nondiabetic participants. There was no significant association between NNRTI use and DM. The frequency of individual PI use was also the same for both diabetic and nondiabetic participants. Among the 69 incident DM cases, only one reported use of megestrol.

Adjusting for known risk factors for diabetes and other HIV- related confounders, a significantly increased risk of DM in all multivariate models was associated with PI use, older age, and larger BMI category. Changes in CD4 cell count and viral load were not independent predictors of DM in HIV-positive women.

"This study found that PI use is an independent risk factor for self-reported DM, with a threefold increase in risk, a result consistent with other studies. ...In view of the clinical benefits of PI therapy, concern about diabetes per se should not dissuade patients or practitioners from using this potent class of antiretrovirals. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is clearly warranted," the authors concluded.

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Adapted from:
Journal of Acquired Immune Deficiency Syndromes
03.01.03; Vol. 32; No. 3: P. 298-302; Jessica E. Justman; Lorie Benning; Ann Danoff; Howard Minkoff; Alexandra Levine; Ruth M. Greenblatt; Kathleen Weber; Eva Piessens; Esther Robison; Kathryn Anastos

This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.


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