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HIGHLIGHTS OF 40th ICAAC: |
Anti-HIV Drug Side Effects
Researcher Proposes ìSaponin (Escin)î Treatment to Prevent Indinavir Kidney Stones
Researchers from Palma, Spain have proposed that treatment with ìescin (Saponin)î might help to prevent kidney stones from occurring among HIV patients who take indinavir (Crixivan). Escin is a medication used ìworldwideî to treat ìchronic venous insufficiencyî(ìleakyî veins leading to swelling, usually in feet, ankles), according to the researchers. Escin is the main ingredient in ìhorse chestnut seed extract.î The lead author was Professor Feliz Grases of the University de las Islas Baleares. Dr. E. Redondo of Merck (Spain) was a co-author. Professor Grases said that escin and saponins ìcan be used as stabilizers of colloidal suspensions, andÖproposed to avoid formation of aggregates [solids] in uric acid urolithiasisî [kidney stones due to ìgoutî or high uric acid levels].
A total of 47 HIV patients (15% women) were enrolled in the 16-week ìcrossoverî study (patients crossed over into study arms with or without escin). All had an undetectable HIV RNA viral load for at least six months taking a triple combination of indinavir (Crixivan) plus 2 NRTI drugs. Prior to enrollment, 27% of the 47 patients had had a previous kidney stone. The dose of escin that was added was 50 mg twice daily.
Professor Grases measured the amount of time required for indinavir crystals to form in the laboratory using urine from a fresh specimen (ìcrystalluriaî) from study participants at baseline and at 4-week intervals. The results showed the following. At baseline, the mean time for indinavir crystals to form in urine was 10 minutes. The mean crystalluria time while taking escin was not reported, but clearly increased as indicated by an accompanying graph. The mean time to crystalluria while taking escin appeared to be approximately 16 minutes (six minute increase). This effect was not related to urine ìpHî (acid level) or indinavir levels in blood or urine, all of which had no significant changes. There were no reported kidney stones during the study. Discontinuations due to adverse effects (stomach-intestinal) occurred among 6%. Two patients (4%) had HIV RNA rebound during the study. Professor Grases concluded that the results, ìsupport the possibility of preventing indinavir associated nephrolithiasis [kidney stones] by means other than overhydration [additional fluids and] further investigations are necessary.î Unfortunately, the study does not prove that escin prevented indinavir kidney stones in study participants. Whether an increased time to crystal formation in urine in the laboratory would lead to a decreased risk of stones in patients taking indinavir remains to be proven. Regardless, the pilot trial was interesting and escin deserves additional study in this setting.
Reference
Grases F and others. A pilot clinical trial to evaluate the safety and efficacy of a saponin (escin) as inhibitor of the indinavir crystallization in urine HIV-infected patients. Abstract and poster 1641.
Hepatitis C Virus Co-Infection with HIV
Abnormal Liver Changes Occur in HIV/HCV Co-Infected Patients, Even with Normal Liver Enzyme ALT
An increasing number of patients with HIV are also infected with HCV (hepatitis C virus) due to similar routes of transmission. As more patients have ìstableî HIV disease due to HAART (highly active antiretroviral therapy), liver disease due to HCV has become an increasing problem. An abnormal liver enzyme test (ALT, alanine aminotransferase) would suggest liver disease among those infected with HCV. Some physicians may feel that if the ALT were normal, a liver biopsy sample (piece viewed under the microscope) would not be necessary. Much less information is available about patients co-infected with HIV and HCV. Now, in a small study from Allentown, Pennsylvania, researchers have found that 80% of HIV/HCV co-infected patients had an abnormal liver biopsy, even though their liver enzyme test (ALT) was normal. Even though the study was small, the results suggest that among patients co-infected with HIV and HCV, liver damage might be present even when the liver enzyme test is normal. An abnormal liver biopsy would be one requirement for considering treatment for chronic hepatitis C.
The study included 24 patients with HIV/HCV co-infection. Race-ethnic background was 58% Hispanic and 25% African-American. One-third was women. Therapy for HIV was being taken by 83%: almost all of them were taking 3-drug HAART. An abnormal ALT was present in 58%, while the remaining 42% had a normal level. Women and Hispanics were evenly distributed among those with or those without a normal ALT. At the time of liver biopsy, the mean (average) CD4 count was 442 cells per microliter, 58% had an undetectable HIV RNA viral load (limit 50 copies per milliliter) and 71% had an HCV RNA viral load greater than 1 million copies per milliliter. All 24 patients indicated they were not actively drinking alcohol or using intravenous (IV) drugs. The HCV ìgenotypeî was not reported.
The results showed that all 14 patients with an abnormal ALT had an abnormal liver biopsy showing inflammation and fibrosis (scarring). And, 80% of the ten patients with a normal ALT had an abnormal liver biopsy. Both inflammation and fibrosis were present among 60% of those with a normal ALT, and only inflammation was present among 20%. Moderate or severe inflammation and fibrosis was present in 20% of those with a normal ALT.
HIV/HCV co-infected patients with an abnormal liver biopsy due to HCV are at risk for progression of liver disease. A sustained virologic response to dual drug therapy (interferon alfa plus ribavirin) for chronic hepatitis C occurs among approximately 39%. Response rates will likely be higher when ribavirin is taken with a long-acting (ìpegylatedî) interferon alfa that is not yet FDA-approved (Pegasys, Peg-Intron). There are very limited studies evaluating the benefits of dual therapy for HCV among HIV/HCV co-infected patients with stable HIV disease resulting from HAART. In the mean time, even though this study was small, the results suggest that a normal ALT test among HIV/HCV co-infected patients does not necessarily mean that the liver biopsy will be normal.