Most patients in darunavir monotherapy trial stay fully suppressed

The latest data from a European trial using boosted darunavir (DRV/r) as the sole HIV drug have found no evidence of increased treatment failure or of viral loads increasing over time, even when viral loads below the usual limit of detectability were investigated with an ultrasensitive assay.

The latest results from the MONET trial, presented at the recent  Tenth International Congress on Drug Therapy in HIV Infection (HIV10) in Glasgow, contrast with an African trial using boosted lopinavir monotherapy (LPV/r) also presented which, in the absence of viral load testing, found increased rates of viral failure over time.   

The MONET trial randomised 256 patients who had had a viral load under 50 copies/ml for at least six months either to take DRV/r monotherapy or to take monotherapy plus the two most suitable NRTI drugs. The 48-week results, presented this time last year at the European AIDS Conference, found that 87% of people on monotherapy and 89% on combination therapy maintained a viral load under 50 copies/ml – a non-significant difference and the most successful result from a PI monotherapy trial.

Other monotherapy trials have found that while the numbers of patients with detectable viral loads may be similar, a larger number of patients on monotherapy had ‘subliminal’ viral loads – ones below 50 but detectable by ultrasensitive tests – which another study reported this week found that monotherapy was associated with some risk of eventual failure.   

The 96-week results from this study were presented at the Vienna International AIDS Conference this year. They showed that after nearly two years, the study found that 75% of people on monotherapy and 81% on combination therapy had maintained a viral load under 50 copies/ml without changing therapy; when NRTIs were added back in or patients switched to new ones, then 91% on combination therapy and 92% who had taken monotherapy had a viral load under 50 copies.

The Glasgow conference heard that, using an ultrasensitive test that could detect viral loads down to five copies/ml, the investigators found that the proportion of people with low-but-detectable viral loads varied little over the study. At baseline the proportion of patients with a viral load between five and 50 copies/ml was 13% in the monotherapy arm and 17% in the combination therapy arm. At week 96 these proportions were 17% and 15% respectively.

The proportion with viral loads under five copies/ml hardly changed at all. Eighty per cent of patients started monotherapy with viral loads under five copies; the proportion by 96 weeks was 79%. In the combination therapy arm the proportion of patients with viral loads under five copies/ml rose from 79 to 81%.

None of these differences in viral load were statistically significant, and there is thus no sign of a rise in ‘subliminal’ viral loads in patients taking monotherapy. There was very little drug resistance observed during the trial. Three patients acquired protease inhibitor resistance during the trial, one of them on combination therapy, and one acquired a new NRTI mutation.

At the Glasgow conference lead investigator Jose Arribas also presented a new cost-effectiveness analysis showing that if all patients in Spain who would have been eligible for the MONET trial – which means more than six months with undetectable viral load with no history of treatment failure, amounting to 15% of all patients in care – then a year’s drug costs for each patient would be €12,250 rather than €20,650. This would save a total of €46 million a year in drug costs, though the analysis did not take viral load testing, overheads such as healthcare worker costs, or the cost of possible future illness into account.

Another study at Glasgow looked at the efficacy of LPV/r (Kaletra) monotherapy in the clinic, as opposed to on a randomised clinical trial.

The study looked at 77 patients at three Spanish hospitals who were switched to LPV/r monotherapy. They had been virally undetectable for an average of three years, had taken an average of seven previous ARV drugs, had a high average CD4 count (519). After a mean follow-up of 22 months (eleven as a minimum), 88% had maintained a viral load under 50 copies/ml. Of the nine patients who failed, seven admitted to poor adherence, and eight successfully re-suppressed their HIV after re-introducing NRTIs.

References

Clumeck N et al. Low-level viraemia during treatment with darunavir/r monotherapy versus DRV/r + 2NRTIs in the MONET trial. Tenth International Congress on Drug Therapy in HIV Infection in Glasgow, abstract O213, 2010.

Arribas JR et al. Cost-efficacy analysis of the MONET trial using Spanish antiretroviral drug prices. Tenth International Congress on Drug Therapy in HIV Infection in Glasgow, abstract P235, 2010.

Caso A, Arranz A et al. Lopinavir/ritonavir monotherapy in clinical practice. Tenth International Congress on Drug Therapy in HIV Infection in Glasgow, abstract P050, 2010.