Clinical trial NCT01061957: Raltegravir Treatment in Patients Failing Highly Active Antiretroviral Therapy (HAART) in Denmark
Official title: Clinical, Virological and Immunological Course in Danish Patients With Triple Class Failure Receiving Raltegravir as Part of a Salvage Regimen.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Treatment outcome
HIV treatment
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2010-02-03
Enrollment: 96
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: One cohort of HIV patients with virological failure initiating Raltegravir One control cohort of HIV patients initiating HAART for the first time.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: virological suppression and CD4 cell gain
timeFrame: 3,5 years
Secondary outcomes:
measure: Time to first change of initial regimen.
timeFrame: 3,5 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: The Danish HIV Cohort Study, Rigshospitalet
Study officials:
References: