Raltegravir Treatment in Patients Failing Highly Active Antiretroviral Therapy (HAART) in Denmark
Raltegravir Treatment in Patients Failing Highly Active Antiretroviral Therapy (HAART) in Denmark
Raltegravir is the first integrase inhibitor approved for treatment of HIV infected patients
 harboring multiresistant viruses. The drug has been proved effective in both trials and
 clinical settings, but the long-term efficacy is not described and the effect compared to
 treatment in Highly active antiretroviral therapy (HAART) naive patients remains to be
 established.
Highly active antiretroviral therapy (HAART) was introduced more than a decade ago and the
 therapy has decreased mortality and morbidity of HIV patients dramatically. The first HAART
 regimens were combined of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside
 reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Especially the early
 regimes carried a substantial risk of failure and subsequent development of resistance to the
 three drug classes. Thus there has been a need for development of new drugs with activity
 against viruses resistant to the classical HAART regimens either as new drugs from the old
 classes without (or with limited) cross resistance to the older compounds or drugs from new
 classes with new antiretroviral mechanisms. The optimal choice for salvage therapy for HIV
 infected patients has been shown to require at least two, and preferably three, fully active
 drugs. Until recently, salvage regimens used to treat patients harbouring multidrug-resistant
 HIV generally included only one new agent from the classic drug classes added to an optimized
 background therapy which did not contain any fully active agents. This approach, conditioned
 by limited drug options, put patients at high risk of virological failure and resistance to
 the new agent, as well as to other agents in the same drug classes. A breakthrough has been
 the resent development of integrase inhibitors, which is a new class of antiretroviral drugs.
 One of these drugs - raltegravir - has demonstrated its activity in patients with virological
 failure on classical antiretroviral drugs. In the BENCHMARK randomized clinical trials, which
 were conducted in HIV-infected patients with limited treatment options, 62% of patients
 taking raltegravir plus optimized background treatment achieved plasma HIV RNA levels <50
 copies/mL at week 48. Although the drug - often used together with other new drugs - has been
 proved effective in clinical trials and recently in "real life" clinical settings, the
 long-term efficacy is not described and the effect compared to treatment in HAART naive
 patients remains to be established. In a nationwide cohort of HIV infected patients, we
 identified the patients, who initiated raltegravir due to virological failure and a matched
 control cohort of patients initiating HAART for the first time. We compared these two cohorts
 with respect to virological suppression, gain in CD4 count and time to first change of
 initial regimen.
Inclusion Criteria:

 -  Raltegravir cohort patients: From the Danish HIV Cohort Study (DHCS) we included all
 HIV-1 positive patients, who

 1. started raltegravir after 1 January 2006 and before 1 July 2009,

 2. had been treated with HAART previously

 3. had at least two VL tests done prior to initiation of raltegravir treatment,

 4. had virological failure prior to start of raltegravir and

 5. did not participate in randomized clinical trials on raltegravir. Virological
 failure was defined as VL > 500 copies/ml in the two latest VL tests prior to
 raltegravir initiation while on HAART treatment.

 -  Control cohort patients: From DHCS we identified a control cohort of HIV infected
 patients who started HAART for the first time after 1 January 2006 and before 1 July
 2009. From this population we extracted two control patients for each raltegravir
 patient, each matched by gender, race (Caucasian, Black and other), route of HIV
 infection (homosexual, heterosexual, injection drug user (IDU) and other) and age
 (intervals of < 20 years, 20 to 30 years, 30 to 40 years, > 50 years).