Don't use Kaletra in patients with haemophilia if other options available, caution French

The use of the protease inhibitor lopinavir-rintonavir (Kaletra^TM) in patients with haemophilia should be reconsidered if they have other treatment options available, caution French doctors.

The warning, published in the November 7^th edition of AIDS (now available online), follows a retrospective review of the records of 16 HIV-positive people with haemophilia treated with a protease inhibitor who were enrolled in the Tourcoing Clinical Cohort in northern France. The investigators found that the use of Kaletra was associated with a three-fold greater risk of bleeding than other protease inhibitors.

Investigators carried out their review after a 22 year-old patient with severe haemophilia, who was taking a HAART regimen containing Kaletra, died of an intracranial bleed.

Soon after the introduction of protease inhibitors, there were reports of increased bleeding complications in patients with haemophilia who were treated with these drugs. Ritonavir was most associated with this problem, followed by indinavir. Newer protease inhibitors, including nelfinavir, amprenavir and Kaletra were thought to cause this complication less often and have been used to treat HIV-positive people with haemophilia.

A retrospective review of the records of 16 HIV-positive patients with haemophilia was conducted. Median age when the first protease inhibitor was prescribed was 26, and 94% of patients were men. Median CD4 cell count was 196 cells/mm³ and median viral load was 30,000 copies/mL. Individuals had been taking protease inhibitor therapy for a median of two and a half years.

The incidence rate of bleeding with Kaletra was 3.7 per 100 person months (95% CI, 0.70 – 10.84), compared to 0.96 per 100 person months (95% CI, 0.35 – 2.09) for ritonavir, saquinavir, indinavir, nelfinavir, and saquinavir-ritonavir. This three-fold difference was significant (p

A total of six patients received a HAART regimen containing Kaletra, of whom 50% developed at least one bleeding disorder. These patients had been treated with Kaletra for a median of four months when the first bleeding disorder occurred. All the bleeding complications required hospitalisation and one patient died (it is unclear from the investigators article if this was the death mentioned earlier).

At the time of bleeding all three patients has a viral below 1000 copies/mL, but were immunosuppressed, with two patients having a CD4 cell count below 100 cells/mm³. Before taking Kaletra all three patients had a nadir CD4 cell count below 100 cells/mm³.

The investigators speculate that the high bioavailability of Kaletra and the low trough levels of the drug might explain the higher risk of bleeding associated with it. They suggest that further study is needed to confirm this.

They conclude that on the basis of their findings, “it seems advisable to reconsider prescribing lopinavir-ritonavir for haemophilic patients when other therapeutic options are available.” If, however, a patient’s only option is Kaletra then the use of the drug may out-weigh the increased risk of bleeding. In these circumstances patients should be warned of the risks, be closely monitored, and consideration should be given to the prophylactic use of factor VIII concentrate.

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Lopinavir - overview