|
|
 |
|
| Year |
Development
|
|
|
|
|
| <
1995 |
|
No
reports of abnormalities1,2
|
| 1997-1998 |
First
reports of hyperglycemia3,4
|
| 1998 |
Insulin
resistance and diabetes reported5,6
|
| 1999 |
PI
has minor effect on glucose metabolism and insulin sensitivity
|
|
|
Long-term
NRTIs are not associated with abnormalities8
|
|
Significant
hyperinsulinemia occurs in women independent of PI use9
|
• Abnormalities in glucose metabolism are another potential complication
of antiretroviral therapy. Various conditions, such as insulin resistance,
hyperglycemia, and frank diabetes, have been linked with the use of
protease inhibitors.
• Early safety and efficacy trials of ritonavir, for example,
did not report any glucose abnormalities as adverse events.1, 2 A
few years later, in 1997 and 1998, however, the first reports of PI-associated
hyperglycemia started surfacing.3
• By 1998, reports of hyperglycemia and diabetes prompted a warning
to clinicians by the FDA. The condition remained relatively uncommon,
with an incidence of 0.52 per 100 person-months in individuals.4
• In 1998, a cross-sectional study showed insulin resistance
as part of a syndrome of peripheral lipodystrophy and hyperlipidemia
in patients receiving protease inhibitors.5 Another case study report
of 8 patients showed hyperinsulinemia in 3 cases.6
• Most recently, we have gained insight into understanding these
abnormalities more fully. Another cross-sectional study demonstrated
that PI therapy has only a minor impact on glucose metabolism and
insulin sensitivity.7 No abnormalities were associated with long-term
NRTI treatment in another study.8 Finally, a study looking specifically
at women found significant hyperinsulinemia at baseline in HIV-infected
women independent of PI use.9
References:
1. Danner SA, Carr A, Leonard JM et al. A short-term study of the
safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor
of HIV-1 protease. European-Australian Collaborative Ritonavir Study
Group. N Engl J Med. 1995;333:1528-33.
2. Markowitz M, Saag M, Powderly WG et al. A preliminary study of
ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.
N Engl J Med. 1995;333:1534-9.
3. Dube MP, Johnson DL, Currier JS, Leedom JM. Protease inhibitor-associated
hyperglycaemia. Lancet. 1997;350:713-4.
4. Keruly JC, Chaisson RE, Moore RD. Diabetes and hyperglycemia in
patients receiving protease inhibitors. 5th Conference on Retroviruses
and Opportunistic Infections, Chicago, IL; Feb 1 - 5, 1998. Abstract
415.
5. Carr A, Samaras K, Burton S et al. A syndrome of peripheral lipodystrophy,
hyperlipidaemia and insulin resistance in patients receiving HIV protease
inhibitors. AIDS. 1998;12:F51-8.
6. Viraben R, Aquilina C. Indinavir-associated lipodystrophy. AIDS.
1998;12:F37-9.
7. Duong M, Petit JM, Piroth L et al. Lipid evaluation and glucose
metabolism in HIV-infected patients before and after initiation of
protease inhibitor therapy. 39th Interscience Conference on Antimicrobial
Agents and Chemotherapy (ICAAC), San Francisco, CA; Sept 26 - 29,
1999. Abstract 1291.
8. Saint-Marc T, Partisani M, Poizot-Martin I et al. A syndrome of
peripheral fat wasting (lipodystrophy) in patients receiving long-term
nucleoside analogue therapy. AIDS 1999;13:1659-67.
9. Hadigan C, Miller K, Corcoran C et al. Fasting hyperinsulinemia
and changes in regional body composition in human immunodeficiency
virus-infected women. J Clin Endocrinol Metab. 1999;84:1932-7.
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