Raltegravir may have role in PEP if exposure involves drug-resistant HIV

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Raltegravir (Isentress) can be safely used as part of a post-exposure prophylaxis regimen and may be of particular value if the possible exposure involves highly drug-resistant HIV, according to a letter published in the November 30th edition of AIDS.

Raltegravir is the first integrase inhibitor to be approved and its use is currently restricted to patients with extensive experience of antiretroviral therapy. Clinical trials investigating its safety and effectiveness in individuals starting HIV treatment for the first time are currently underway and the interim results are promising.

Doctors from Washington State in the USA have explored another possible use for raltegravir – as part of a post-exposure prophylaxis regimen following possible occupational exposure to HIV.

Glossary

post-exposure prophylaxis (PEP)

A month-long course of antiretroviral medicines taken after exposure or possible exposure to HIV, to reduce the risk of acquiring HIV.

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.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

occupational exposure

Exposure to HIV as a result of work (job) activities. Exposure may include accidental exposure to HIV-infected blood following a needlestick injury or cut from a surgical instrument

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.

Two cases when raltegravir was used effectively and safely as part of a post-exposure prophylaxis are reported by the doctors. They occurred between July 2007 and January 2008 and both cases involved possible exposure from the same highly treatment-experienced patient with drug-resistant virus.

The first healthcare worker experienced a deep wound when removing a venous catheter from the patient, whose viral load was 215,000 copies/ml at the time. Raltegravir was not licensed at this time, so special permission had to be obtained for its use as part of a post-exposure prophylaxis regimen. This regimen also included atazanavir (Reyataz) boosted by ritonavir, plus Truvada (tenofovir and FTC). However, because of nausea and hyperbilirubinaemia treatment with atazanavir/ritonavir was stopped and therapy with Truvada and raltegravir was provided for 28 days.

The second case involved a laboratory worker who was cut by a test tube containing the patient’s blood. This individual received treatment with a well-tolerated post-exposure prophylaxis regimen including darunavir (Prezista), boosted by ritonavir with Truvada and raltegravir.

Neither individual became infected with HIV. The authors write, “raltegravir was well tolerated in these two occupational exposures and appears to be an optimal choice for these individuals exposed to blood from an HIV patient with extensive drug resistance, given its novel mechanism of action, potent and rapid killing of HIV, and favourable side-effect profile.”

References

Siegel MO et al. Raltegravir for postexposure prophylaxis following occupational exposure to HIV. AIDS 22: 2552-54, 2008.