Supplements containing glutamine or alanyl-glutamine can improve the diarrhoea and reduced absorption of antiretroviral drugs seen in AIDS patients, according to a Brazilian study published in the June 15th edition of Clinical Infectious Diseases.
The amino acid glutamine is known to help protect and repair the gut wall and to improve absorption. While glutamine is poorly soluble and unstable in solution, this study demonstrated that its more stable derivative alanyl-glutamine, when given in a high dose, is as effective as glutamine in alleviating the chronic diarrhoea and wasting seen in AIDS patients. This, in turn, increases the absorption of antiretroviral drugs in the gut.
“The dose-related efficacy of alanyl-glutamine and glutamine in treating diarrhoea and in increasing antiretroviral drug levels shows that these supplements may help to improve therapy for patients with AIDS who have diarrhoea and/or wasting in developing, tropical areas,” conclude the authors.
The investigators recruited 41 HIV-positive patients who were taking antiretroviral therapy from Hospital São Jose in Ceará, Brazil for their randomised controlled trial, between March 2001 and April 2002. All the patients had diarrhoea (more than three stools per day for over 14 days) and wasting (loss of more than 10% of body weight). The patients were aged between 23 and 52 (median 36), and 12 (29%) were female.
The patients were randomised to receive 30g glutamine, 4g of alanyl-glutamine or 44g of alanyl-glutamine orally per day. A control group received 46g of the amino acid glycine per day. Glycine has no effect on diarrhoea, but this dose contains the same amount of nitrogen as the higher dose of alanyl-glutamine. Glycine was also added to the glutamine and low-dose alanyl-glutamine regimens to equalise the amount of nitrogen received by all the patients.
The patients were asked about the frequency and consistency of their diarrhoea every day. Eight (89%) of nine patients in the high-dose alanyl-glutamine group showed an improvement in symptoms, compared with three (38%) of eight in the control group (p
On the third day of treatment, blood samples were taken from all the patients, two hours after antiretroviral drug dosing. Levels of antiretroviral drugs were measured in samples from 33 patients and compared with levels from matched control patients without diarrhoea or wasting.
The patients with diarrhoea and wasting had lower levels of didanosine (ddI; mean 397 vs. 737ng/ml; p
After seven days of treatment with the dietary supplements, nine (75%) of twelve levels of NRTIs had increased in patients taking high-dose alanyl-glutamine. This was compared to two (15%) of 13 in the glycine control group (p = 0.009). In the low-dose alanyl-glutamine group, eleven (55%) of 20 drug levels had increased (p = 0.056), and nine (64%) of 14 levels had increased in the glutamine group (p = 0.028). Similar patterns were observed when protease inhibitor and NNRTI levels were included in this analysis.
Overall, drug levels increased by a mean of 113% in the high-dose alanyl-glutamine group, compared with a decrease of 32% in the control glycine group (p = 0.02). The low-dose alanyl-glutamine group showed a mean increase of 8% (p = 0.06) and the glutamine group 14% (p = 0.01). These findings were mirrored by increases in intestinal absorption, measured by mannitol excretion in the urine.
Following genotyping of the HIV from 16 of the patients, 45 (69%) of the 65 resistance mutations found were associated with low levels of the corresponding drug, with most patients showing resistance mutations to more than one drug. This confirms that low levels of circulating antiretroviral drugs, which may be caused by poor intestinal absorption, increase the chances of the development of drug resistance and treatment failure.
Despite the small size of the study, the authors are optimistic about their findings. “These improvements [in diarrhoea and malabsorption] may enhance antiretroviral drug therapy and reduce the emergence of drug resistance in patients with HIV/AIDS in tropical, developing areas.”
However, it is not clear from this study report how long the supplements would need to be taken to bring about a long-term improvement in diarrhoea and drug absorption, or whether the cost of the supplements may limit their widespread use in developing countries.
Further information on this website
Glutamine - overview
Diarrhoea - overview
Wasting syndrome - overview
Reference
Bushen O Y et al. Diarrhea and reduced levels of antiretroviral drugs: improvement with glutamine or alanyl-glutamine in a randomized controlled trial in northeast Brazil. Clin Infect Dis 38: 1764-1770, 2004.