Gout and HIV: another symptom of lipodystrophy

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People taking the protease inhibitor saquinavir boosted by ritonavir are at risk of developing gout, particularly if they have body fat changes caused by HIV treatments, according to research presented to the 9th annual conference of the British HIV Association.

Gout is often thought of as a disease of the past, brought on by high living and a diet consisting of game, cheeses and fine wines. However, gout has been observed in HIV-negative people with a metabolic syndrome similar to the lipodystrophy syndrome seen in HAART treated HIV-positive patients. There have also been reports of gout occurring in HAART-treated patients, particularly in patients taking the protease inhibitor ritonavir or protease inhibitors boosted by the drug.

Although symptoms of gout are popularly considered no more serious than a painful, swollen big-toe, the disease can be debilitating, causing disability and deformed joints.

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

lipodystrophy

A disruption to the way the body produces, uses and distributes fat. Different forms of lipodystrophy include lipoatrophy (loss of subcutaneous fat from an area) and lipohypertrophy (accumulation of fat in an area), which may occur in the same person.

syndrome

A group of symptoms and diseases that together are characteristic of a specific condition. AIDS is the characteristic syndrome of HIV.

 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

Investigators at the Mortimer Market Centre, London, one of the UK’s largest HIV treatment centres, conducted a retrospective chart review of their entire cohort of 1,800 patients to establish the prevalence and risk factors for gout. Over 1,000 patients at the clinic were taking HAART. Risk factors for gout, including age, sex, CD4 cell count, HIV viral load, stage of HIV-disease, type and duration of anti-HIV therapy, treatment for HIV-related opportunistic infections, and lipodystrophy were recorded. In total 18 patients were found to have developed gout, 13 of whom were taking HAART.

Average CD4 cell count in the patients with gout was 367 cells/mm3 and viral load a little over 13,000 copies/ml, and uric acid production was double the normal range. Patients had been taking HAART for an average of 41 months.

When the investigators analysed the drugs the patients with gout were taking, they found that eight had predisposing factors including pyrazinamide treatment for TB, whilst seven were receiving ritonavir-boosted PIs. Patients with gout were significantly more likely to be taking boosted saquinavir than patients not affected by gout (50% versus 10%; P=0.00001)

The presence of body fat changes was also found to be associated with gout, as 88% of the patients with gout also had evidence of fat loss.

The investigators conclude that gout occurs with increased frequency in HIV-positive patients who have progressed to an AIDS diagnosis and are treated with a ritonavir-boosted PI and recommend that patients taking these drugs who complain of joint pain are evaluated for gout.

Further information on this website

Lipodystrophy - comprehensive overview

Ritonavir - overview

Saquinavir/ritonavir - key research

References

Creighton S et al. Gout and HIV: A new facet of fat redistribution syndrome? Poster Presentation P12, 9th Annual Conference of the British HIV Association, 2003.