New treatment for oral thrush as effective as current standard of care, and better at preventing relapse

A new oral treatment for oral candidiasis is as effective as the current standard of treatment and may be even better at preventing relapse in HIV-positive individuals, according to an international, randomised, blinded study published in the April 15^th edition of Clinical Infectious Diseases.

Oral thrush is the most common opportunistic infection seen in HIV-positive individuals. Topical, oral and intravenous treatments for candida infections of the mouth and oesophagus are available. The current standards of care are fluconazole or itraconazole, but resistance to these drugs can develop.

Laboratory studies have shown that the orally administered posaconazole is effective against the species of Candida that cause oral candidiasis. Investigators therefore designed a study comparing the efficacy and safety of posaconazole with fluconazole. The study’s primary aim was to compare the proportion of HIV-positive patients with oral candida who experienced an improvement or cure of their oral candida after 14 days of treatment. The investigators also assessed the durability of the two therapies and looked at rates of relapse in the two treatment arms after 42 days. The impact of posaconazole and fluconazole on candida cultured from patients enrolled in the study was assessed at day 14 and again at day 42. Safety data for the two treatments were also gathered.

A total of 350 individuals were recruited to the study at 47 world-wide sites between late 1998 and late 1999. Only a third of patients were taking antiretroviral therapy of any kind and the median CD4 cell count on entry to the study was 134 cells/mm³, indicating that patients had a high risk of opportunistic infections, including oral candidiasis.

Patients were equally randomised into the two treatment arms. Therapy with an 200mg oral suspension of their allocated study drug was provided on day one followed by 14 days of treatment consisting of a once-daily 100mg oral dose.

After the completion of 14 days of therapy, clinical success occurred in 92% of patients treated with posaconazole and 93% of individuals who received fluconazole. The difference was not statistically significant and the results demonstrated that posaconazole was non-inferior to fluconazole.

Fewer patients who took posaconazole experienced a relapse (32%) after 42 days compared to those who took fluconazole (38%), but the difference was not statistically significant.

The investigators then looked at the results obtained from culture. These showed a 68% success rate in both treatment arms at day 14. By day 42, however, significantly more patients who received posaconazole had negative culture results (41%) than those who received fluconazole (26%, p = 0.038). Culture results showed eradication in 36% of posaconazole-treated patients versus 24% of those who received fluconazole, but this difference did not reach statistical significance (p = 0.084).

Discontinuation rates (12%, posaconazole versus 11%, fluconazole) were comparable, as was the incidence of side-effects. There were no serious side-effects attributable to the use of either drug, not did either drug cause any serious laboratory abnormalities.

“The results of this study demonstrate that posaconazole was as effective as fluconazole in producing a successful clinical outcome in HIV-1 infected subjects with oropharyngeal candidiasis”, write the investigators, who add, “posaconazole appears to be more effective than fluconazole in sustaining a successful clinical outcome and maintaining a symptom-free period after discontinuation of treatment.”

An accompanying editorial praises the study as “well-conceived and well-conducted.”