Of course these side effects of 'protease paunch' or 'crix belly' deserve further investigation and should not have been viewed as "a cosmetic concern" when patients first complained. They may indicate an underlying abnormal lipid metabolism. However, unless this condition turns out to be an omen of serious complications, the treatment is still much better than the alternative..
Seven studies presented data at the 5th Conference on Retroviruses on the topic. There were 128 cases of 'Protease Paunch" reported in the abstracts, and 109 patients were on either Crixivan, Ritonavir, or Saquinavir. Only 2 or 3 patients were on Viracept. Some studies did not specify which drugs were involved.
The reported time to diagnosis of these fatty deposits ranged from one month to 18 months, with many cases appearing between 4-6 months. Viracept has been approved for almost one year so one would think a significant number of cases should have been reported by now. More cases will be reported as awareness of the condition grows, and maybe it will turn out that an equal number of patients on Viracept will develop this, however the abstracts presented at the meeting certainly do not indicate this, nor do all the authors feel this will be the case, as you imply.
From the abstracts:
1. Abstract 407, Hengel et al, Emory; 4 cases reported of lipomatosis, 4 on crixivan;
In a recent letter to the Lancet, 11/29/97 , discussing one patient, they conclude, "The temporal association between starting his medications and developing his 'buffalo hump,' the effect of protease inhibitors on P450 enzymes, and the recent associations between indinavir use and glucose and lipid metabolism lead us to believe indinavir may be implicated in the development of benign symmetric lipomatosis."
Median time on therapy prior to diagnosis was 6 months.
2. Abstract 408, Rosenberg et al, Cornell; 120 patients observed; 5 cases of ProTease -Paunch were reported in 72 patients on protease inhibitors; the specific drugs were not specified.
Median time on PI therapy was 18 months.
3. Abstract 409: Lo et al; UCSF; 7 cases of 'Buffalo Hump' were reported; 4 patients were on older nucleosides, 3 on protease inhibitors which were not specified. She does not feel it is pi specific, and reports cases on nucleosides as well.
4. Abstract 410: Carr et al, St. Vincent's, Australia; observed 148 patients, 72 cases of Peripheral Lipodystrophy, (LD) reported; 72 were on Crixivan, Indinavir, or Saquinavir (numbers on each not given). None were reported on Viracept.
Occurred after a mean of 10 months.
LD developed earlier and was more severe in patients on Ritonavir-Saquinavir than on Crixivan. Those with LD had higher TG, cholesterol, insulin, and c-peptide and insulin resistance scores.
5. Abstract 411: Roth et al, Ottawa; followed 800 patients, 2/3 on protease inhibitors, followed from 11/96 to 8/97. 7 patients developed a Cervical Fat Pad; at least one each of crixivan, saquinavir, ritonavir, nelfinavir. Did not think it was specific to a particular protease inhibitor.
Reported at a median of 19 weeks, (4-61 week range)
6. Abstract 412: Mann et al, FDA; 9 patients on protease inhibitors; 2 on saquinavir, 2 on ritonavir, 5 on crixivan (l on crixivan later switched to nelfinavir)
Symptoms within 1-6 months of therapy
One patient discontinued protease inhibitors and the symptoms did resolve.
7. Abstract 413: Miller et al, National Institute of Health, 24 cases reported on indinavir. They concluded that "HIV-infected patients on long-term indinavir experience an accumulation of visceral fat that may cause abdominal complaints. It is not known whether similar abnormalities are associated with other HIV protease inhibitors. "
8. Abstract 414: Evidence of Unique Metabolic Effects of Protease Inhibitors
Mulligan et al; UCSF; compared those on PI's and 3TC to no HAART.
Glucose, triglyceride, and cholesterol levels were elevated in the group on Protease inhibitors and suggests abnormal lipid metabolism.
Maybe it time to focus on some new topics, such as the research on chemokines, chemokine co-receptors, immune therapy, gene therapy, anti-sense therapy, hydroxyurea. There is optimism now that it may be possible eventually to flush the hidden reservoirs that contain HIV virus, in patients who are 'undetectable' on HAART therapy. This was a subject of great concern several months ago.....yet has received very little attention here. |
