Raltegravir is the first approved HIV integrase inhibitor, and is indicated in the treatment of HIV infection in combination with other antiretroviral agents in treatment-naive patients and treatment-experienced patients with evidence of HIV replication despite ongoing antiretroviral therapy. Raltegravir is active against HIV-2 and a wide range of wild-type and drug-resistant HIV-1isolates, including both CCR5 coreceptor–using strains and CXCR4 coreceptor–using strains. Additive to synergistic activity against HIV-1 was observed when raltegravir was combined with other antiretroviral agents.  

 

Raltegravir is metabolized through glucuronidation, and drugs inducing glucuronidation enzyme, UGT1A1, such as rifampin, significantly reduce raltegravir concentration and should not be used. Phenytoin and Phenobarbital also have similar effects, but this has not been well investigated. Despite interactions between raltegravir and selected antiretroviral drugs, such as tenoovir, efaviranz, etravirine, atazanavir, ritonavir, tipranavir, none of these interactions are thought be clinical significant. 

 

It has been confirmed that significant resistance to raltegravir is the consequence of multiple integrase gene substitutions. Three main drug-resistance pathways associated with treatment failure has been demonstrated. Although clinical data on cross-resistance to other integrase inhibitor, such as elvitegravir, are lacking, certain resistance pathways produce high-level phenotypic resistance to both drugs.

 

The most common adverse events were transient mild-to-moderate headache and fatigue. A higher percentage of grade 3 and 4 creatine phosphokinase elevations while less significant changes in lipid levels has been reported in the raltegravir arm than in the efavirenz arm over 96 weeks. To date, no strong evidence supports raltegravir is associated with the development of malignancies despite mildly higher incidence of cancer in the early report. 

 

Raltegravir: the first HIV type 1 integrase inhibitor Hicks C, Gulick RM. Clin Infect Dis. 2009 Apr 1;48(7):931-9.

This article concisely summarized current publications of raltegravir regarding its clinical pharmacology, drug interactions, clinical trials, safety, toxicities, drug resistances, and clinical uses.

 

Review of Cancer Incidence in Raltegravir Clinical Trials. Cooper D, Steigbigel R, Lennnox J et al. Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montréal, Canada. Abstract 859.

Development of malignancies has been a concern of raltegravir use, and this extensive review demonstrated no difference in risk for cancer in HIV-positive patients treated with raltetravir or other antiretroviral therapy by summarizing the cancer rates from available data of multiple clinical studies.