HIV-positive women taking protease inhibitors are three times more likely to develop diabetes than HIV-positive women on non-protease inhibitor combinations or HIV-negative women, according to a US study published in the March 2003 edition of the Journal of Acquired Immune Deficiency Syndromes.
Investigators assessed 1435 HIV-positive women and 350 HIV-negative women with similar HIV risk factors as controls to determine the relationship between diabetes and risk factors such as the use of anti-HIV drugs, virologic response to therapy, age and weight. The study was part of the Women’s Interagency HIV Study (WIHS).
Women were recruited to the WIHS cohort at six clinics in large US cities between 1994 and 1998. The HIV-positive women were divided into three groups, reflecting their HIV treatment history. These were: patients who had been treated with a protease inhibitor; patients who had received anti-HIV therapy using NRTIs and NNRTIs only; and patients with no experience of anti-HIV drugs. The fourth group in the study were HIV-negative women.
Follow-up was provided with six-monthly visits, when women were asked to report if they had developed diabetes. At these visits the women were also weighed.
Age and ethnicity were comparable between the HIV-positive and HIV-negative women, however the HIV-positive women weighed less at baseline and had a lower body mass index with the HIV-negative women were more likely to be obese (33% versus 23%).
At baseline, a CD4 cell count of below 200 cells/mm3 was recorded in 27% of the HIV-positive patients and 34% had a viral load below 4,000 copies/ml. Use of protease inhibitor regimens increased throughout the four years of the study from only 0.3% of the sample in 1994 to 45% by 1998, reflecting the advances made in anti-HIV therapy during the period of the study, and the increased availability of protease inhibitors.
In total 69 new cases of diabetes were reported amongst the study participants. The investigators calculated incidence per patient year. The 1785 women in the study gave a total of 4578 patient years of follow-up. The overall incidence of diabetes was 1.5 cases per 100 patient years of follow-up.
Women treated with protease inhibitors had a three-fold increased risk of developing diabetes, with 2.8 cases per 100 patient years, compared to 1.4 per 100 patient years in the HIV-negative group, 1.2 per 100 patient years in the NRTI arm and 1.2 per 100 patient years in HIV-positive women who received no HIV therapy.
Obese and morbidly obese women were also found to have an increased risk of developing diabetes, but when these data were adjusted for anti-HIV drug use, women who used protease inhibitors were still found to be at increased risk compared to those treated with non-protease regimens.
45% of women reported first symptoms of diabetes at the same follow-up visit as first protease inhibitor use.
The risk of developing diabetes did not seem to be linked to either virologic response to therapy or weight gain whilst on anti-HIV drugs. A virologic response to therapy occurred in 25% of diabetic patients and 28% of non diabetic patients not treated with protease inhibitors and in 53% of diabetic and 52% of non-diabetic patients treated with protease inhibitors.
No single anti-HIV drug (other than protease inhibitors as a class), was found to be predictive of the development of diabetes.
”This study found that PI use is an independent risk factor for self reported” diabetes note the authors, concluding that monitoring for diabetes is warranted amongst women treated with protease inhibitors, particularly if they have other risk factors for the condition, such as older age and obesity.
The authors note that self-reporting of diabetes may have led to an underestimate of incidence.
Further information on this website
Justman JE et al. Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women. Journal of Acquired Immune Deficiency Syndromes, 32: 298 – 302, 2003.