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

Abstract

Introduction: The antiretroviral treatment paradigm for human immunodeficiency virus-1 (HIV-1) infection has undergone a significant change with the addition of a new class of therapeutic agents targeting HIV-1 integrase (IN). IN inhibitors prevent the integration of viral DNA into the human genome and terminate the viral life cycle. As the first member of this new class of anti-HIV drugs, raltegravir has shown promising results in the clinic.

Aims: To review the emerging evidence for the use of the IN inhibitor raltegravir in the treatment of HIV-1 infection.

Evidence review: Strong evidence shows that raltegravir is effective in reducing the viral load to less than 50 copies/mL and increasing CD4 cell count in treatment-experienced patients with triple-drug class-resistant HIV-1 infection. Substantial evidence also indicates that while raltegravir is able to achieve treatment response in patients with drug-resistant HIV-1, it is susceptible to development of resistance. Raltegravir should be used with at least one other active drug. In addition to its use in salvage therapy upon failure of first-line antiretroviral treatment, a raltegravir-based treatment regimen may also be effective as initial therapy. Substantial evidence also shows that raltegravir-based treatment regimen is well tolerated with minimal clinically severe adverse events and toxicities. Modeling studies suggest a cost-effectiveness of US$21,339 per quality-adjusted life year gained with raltegravir use, though further direct evidence on quality of life and cost-effectiveness is needed.

Place in therapy: 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.

Keywords: HIV-1; MK-0518; clinical evidence; integrase inhibitor; isentress; raltegravir.

Figure 1

Efficacy of raltegravir as part of combination therapy in treatment-naive patients at week 48 of treatment.

Figure 2

Efficacy of raltegravir in treatment-experienced patients with triple-class drug resistance. Notes: p < 0.001 between the treatment groups for all the studies. Abbreviation: OBT, optimized background therapy.

Figure 3

Relative fold change in susceptibility to raltegravir.