[pronut-hiv] Darunavir (TMC114) approved for use in treatment-experienced patients in US

["ProNut-HIV" <pronut-hiv@healthnet.org>]

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Darunavir (TMC114) approved for use in treatment-experienced patients
in US 

The United States Food and Drug Administration (FDA) granted
accelerated approval of the new protease inhibitor darunavir on Friday.
Darunavir, which was known as TMC114 during development and will be
marketed as Prezista, will now be available for HIV-positive patients in
the United States whose infection is not responding to treatment with
other anti-HIV drugs. 

This approval will come as good news for HIV-positive patients in the
United States who have few treatment options available after failure of
previous drug combinations. 

The recommended dose for darunavir is 600mg twice a day. Each dose must
be taken at the same time as 100mg ritonavir (Norvir) and with food. The
small dose of ritonavir decreases the breakdown of darunavir in the
liver, resulting in higher levels of the drug in the blood. Darunavir is
produced in orange tablets containing 300mg of the active drug. 

Darunavir is not yet approved for use in children, or in patients who
have not taken any anti-HIV drugs before. 

The approval of darunavir was granted after the drug's manufacturer,
Tibotec Inc., presented data from two randomised studies to the FDA.
These studies, called TMC114-C213 (POWER 1) and TMC114-C202 (POWER 2),
looked at the risks and benefits of the drug in patients with
substantial treatment experience, finding that patients taking
ritonavir-boosted darunavir had larger reductions in their viral loads
than patients taking other ritonavir-boosted protease inhibitors. 

Taken together, the two studies found that 70% of the patients taking
darunavir had a viral load reduction of at least 1 log10 after 24 weeks.
This was in contrast to only 21% of the patients taking another protease
inhibitor. The patients taking darunavir also had larger increases in
CD4 cell count (92 vs. 17 cells/mm3). 

Both groups of patients took their protease inhibitors with other
anti-HIV drugs, including nucleoside reverse transcriptase inhibitors
(NRTIs), chosen on the basis of genetic testing. Almost half of the
patients also took the fusion inhibitor T-20 (enfuvirtide, Fuzeon). 

The main side-effects seen in the studies were diarrhoea, nausea and
headache. Around 7% of the patients also had skin rashes. These were
serious in a few cases. 

Darunavir should not be taken with other drugs that are broken down
through the cytochrome 3A system. These include many prescription and
non-prescription drugs, as well as certain herbal products such as St
John's wort. Other drugs may need to be taken at non-standard doses
with darunavir. 

Accelerated approval is granted for drugs that are likely to have a
significant benefit for patients, before all of the formal studies into
its efficacy and safety have been completed. 

As a condition of the accelerated approval, Tibotec has agreed to carry
out more studies into darunavir's activity, particularly in children
and in patients with liver damage. Tibotec will also carry out more
studies into interactions between darunavir and other drugs. 

Approval of darunavir in the European Union is expected later this
year.