Diabetes in HIV Positive Women Linked to NRTIs, Not Protease Inhibitors

By Liz Highleyman

Many studies have assessed the link between antiretroviral therapy and various metabolic complications in people with HIV. It is commonly thought that blood glucose abnormalities such as insulin resistance and type 2 diabetes are associated with protease inhibitors, but a recent study calls this assumption into question.

As reported in the August 20, 2007 issue of AIDS, researchers assessed the incidence of type 2 ("adult onset") diabetes mellitus in the Women's Interagency HIV Study (WIHS), a nationally representative cohort of HIV positive women in the U.S. and a comparison group of HIV negative women at risk for infection.

This prospective study, conducted between October 2000 and March 2006, included 2088 WIHS participants who did not have evidence of diabetes at enrollment (1524 HIV positive and 564 HIV negative). Compared with HIV negative women, the women with HIV were older and more likely to be coinfected with hepatitis C virus (both factors associated with diabetes), but also had a lower body mass index (a protective factor).

All participants were assessed at semi-annual study visits, including fasting glucose levels and body measurements. Incident (new-onset) diabetes was defined as having fasting glucose > 1.26 g/l, use of anti-diabetic medication, or a confirmed self-reported diabetes diagnosis.

Results

• Diabetes developed in 116 HIV positive women and 36 HIV negative women over 6802 person-years of follow-up.

• HIV positive women reporting no recent antiretroviral therapy had a diabetes incidence rate of 1.53 per 100 person-years.

• Those receiving monotherapy or dual therapy (rather than standard HAART regimens) had the highest incidence rate, at 3.40 per 100 person-years.

• Women on HAART regimens containing a protease inhibitor had an incidence rate of 2.50 per 100 person-years.

• Those taking non-PI-containing (protease-sparing) HAART regimens had an incidence rate of 2.89 per 100 person-years.

• None of these rates differed "substantially or beyond levels expected by chance" from that of HIV negative women (1.96 per 100 person-years).

• Among HIV positive women, longer cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTIs) was associated with an increased risk of new-onset diabetes compared with no NRTI exposure (relative hazard 1.81 [95% CI 0.83-3.93] for 0-3 years of exposure, and 2.64 [95% CI 1.11-6.32] for > 3 years of exposure).

• Looking at specific NRTIs, only use of 3TC (Epivir) was associated with incident diabetes (relative hazard 2.81 [95% CI 1.33-5.95] for > 1 year of exposure).

• Neither protease inhibitors nor NNRTIs were linked to a higher rate of diabetes.

Conclusion

"Longer cumulative exposure to NRTI was associated with increased diabetes mellitus incidence in HIV-infected women," the study authors concluded. "Regular diabetes mellitus monitoring is advisable because NRTI form the backbone of effective antiretroviral therapy."

The researchers suggested that the increased incidence of diabetes among women with prolonged NRTI exposure may be related to mitochondrial toxicity. However, this type of toxicity has been more strongly linked to AZT (Retrovir), d4T (Zerit), ddI (Videx), and ddC (Hivid, now discontinued) than to 3TC.

University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Southern California, Los Angeles, CA; CORE Center/Stroger Hospital of Cook County, Chicago, IL; State University of New York-Downstate Medical Center, Brooklyn, NY; Georgetown University Medical Center, Washington, DC; Columbia University, NY.

09/07/07

Reference
PC Tien, MF Schneider, SR Cole, and others. Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women's Interagency HIV Study. AIDS 21(13): 1739-1745. August 20, 2007.