Raltegravir with optimized background therapy for resistant HIV-1 infection.

@article{Steigbigel2008RaltegravirWO,
  title={Raltegravir with optimized background therapy for resistant HIV-1 infection.},
  author={Roy T. Steigbigel and David A. Cooper and Princy N. Kumar and Joseph E Eron and Mauro Schechter and Martin H. Markowitz and Mona Loutfy and Jeffrey L. Lennox and Josep Mar{\'i}a Gatell and J{\"u}rgen K. Rockstroh and Christine Katlama and Patrick G Yeni and Adriano Lazzarin and Bonaventura Clotet and Jing Zhao and Joshua Chen and D. M. Ryan and Rand R. Rhodes and John A Killar and Lucinda R Gilde and Kim M. Strohmaier and Anne R. Meibohm and Michael D. Miller and Daria J Hazuda and Michael L. Nessly and Mark J. Dinubile and Robin D. Isaacs and Bach Yen Nguyen and Hedy Teppler},
  journal={The New England journal of medicine},
  year={2008},
  volume={359 4},
  pages={
          339-54
        }
}
BACKGROUND Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs. METHODS We conducted two identical trials in different geographic regions to evaluate the safety and efficacy of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that has triple-class drug resistance in whom antiretroviral therapy had failed… 

Tables from this paper

Raltegravir: the first HIV type 1 integrase inhibitor.

  • C. HicksR. Gulick
  • Biology, Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2009
TLDR
Raltegravir is the first approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor; it targets the strand transfer step of HIV-1 integration and is metabolized by glucuronidation, not hepatically; thus, the potential for drug-drug interactions is decreased.

Raltegravir: The evidence of its therapeutic value in HIV-1 infection

TLDR
Raltegravir shows significant and sustained virologic and immunologic response in combination with other antiretrovirals in treatment-experienced HIV-1 infected patients who show evidence of viral replication or multidrug-resistant HIV- 1 strains, without any significant tolerability issues.

Cost–effectiveness of raltegravir in HIV/AIDS

TLDR
It is suggested that raltegravir, combined with optimized background therapy, falls within the range that would generally be considered cost effective compared with optimized therapy alone in Spanish, Swiss and UK health systems.

Raltegravir as functional monotherapy leads to virological failure and drug resistance in highly treatment-experienced HIV-infected patients

TLDR
If persistent low viraemia is observed over more than 48 weeks without the emergence of resistance, RAL should never be given as functional monotherapy, as it is associated with a maximal risk of VF and the emergenceof RAL resistance.

Similar Efficacy of Raltegravir When Used With or Without a Protease Inhibitor in Treatment-Experienced Patients

TLDR
In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI had similar virologic activity when compared to more standard regimens using ralgegravIR with a PI, and the main determinant of efficacy was the number of active drugs as measured by GSS.

Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study

TLDR
These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL, and dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen.

Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1-infected patients: a randomized open-label trial.

  • N. De CastroJ. Braun J. Molina
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2009
TLDR
A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy.

Raltegravir dosage adjustment in HIV-infected patients receiving etravirine.

  • V. DoR. HigginsonP. Fulco
  • Medicine
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2011
TLDR
In patients who have an extensive history of HIV disease treatment, prescribing raltegravir 1200 mg/day, rather than the standard 800 mg/ day, may be prudent to prevent the development of treatment-resistant virus and to achieve an optimal virological response.

Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy

TLDR
Raltegravir improved the clinical management of HIV-1 infection both in antiretroviral-naïve and in antiresistant patients, and had a favorable safety and tolerability profile.

Virologic Outcomes of Changing Enfuvirtide to Raltegravir in HIV-1 Patients Well Controlled on an Enfuvirtide Based Regimen: 24-Week Results of the CHEER Study

TLDR
In treatment-experienced patients on a stable virologically suppressive enfUVirtide-containing regimen, raltegravir can safely be substituted for enfuvirtide in HIV-1-infected patients.
...

References

SHOWING 1-10 OF 78 REFERENCES

Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection.

TLDR
When combined with an optimized background regimen in both studies, a consistently favorable treatment effect of raltegravir over placebo was shown in clinically relevant subgroups of patients, including those with baseline characteristics that typically predict a poor response to antiretroviral therapy: a high HIV-1 RNA level, low CD4 cell count, and low genotypic or phenotypic sensitivity score.

Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia.

TLDR
The addition of enfuvirtide to an optimized background regimen provided significant viral suppression and immunologic benefit over a 24-week period in HIV-1-infected patients who had previously received multiple antiretroviral drugs.

Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America.

TLDR
The addition of enfuvirtide to an optimized antiretroviral and immunologic benefit through 24 weeks in patients who had previously received multiple antireTroviral drugs and had multidrug-resistant HIV-1 infection.

Raltegravir With Optimized Background Therapy for Resistant HIV-1 Infection

TLDR
There are compelling reasons for expanding the anti-HIV armamentarium and the safety and effectiveness of raltegravir, an inhibitor of HIV integrase, an enzyme essential in the cycle of HIV replication, is evaluated.

Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211.

TLDR
In HIV-1-infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks and the relationship of vicrivIROc to malignancy is uncertain.

Rapid and Durable Antiretroviral Effect of the HIV-1 Integrase Inhibitor Raltegravir as Part of Combination Therapy in Treatment-Naive Patients With HIV-1 Infection: Results of a 48-Week Controlled Study

TLDR
Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate.

Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-week analysis from the RESIST-1 trial.

  • J. GatheD. Cooper D. Mayers
  • Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2006
TLDR
TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.

Ritonavir-boosted tipranavir demonstrates superior efficacy to ritonavir-boosted protease inhibitors in treatment-experienced HIV-infected patients: 24-week results of the RESIST-2 trial.

  • P. CahnJ. Villacian D. Mayers
  • Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2006
TLDR
TPV/r had superior antiviral activity and increased immunologic benefits, compared with CPI/r, at week 24 among treatment-experienced patients infected with multidrug-resistant HIV-1.

Antiretroviral Activity, Pharmacokinetics, and Tolerability of MK-0518, a Novel Inhibitor of HIV-1 Integrase, Dosed As Monotherapy for 10 Days in Treatment-Naive HIV-1-Infected Individuals

TLDR
MK-0518 showed potent antiretroviral activity as short-term monotherapy and was generally well tolerated at all doses, and part 2 of the study, a dose-ranging 48-week trial of MK-05 18 versus efavirenz in a combination regimen, has been initiated.
...