Raltegravir in treatment-naive patients
5 October 2009. Related: Conference reports, Antiretrovirals, IAS 5th Cape Town 2009.
Simon Collins, HIV i-Base
In July 2009, raltegravir was approved in the US as first-line therapy, and also received a positive opinion from the CHMP for a similar indication in Europe, based on 48-week results from the STARTMRK trial. [5, 6]
In summary, raltegravir showed similar virological efficacy compared to efavirenz (86% vs 82% <50 copies/mL at week 48), when used with tenofovir+FTC. [7]
At the IAS conference, longer-term safety data was available from 144-week follow-up from the initial dose-finding study (Protocol 004), where, after the first year, all patients (n=160) were switched to, or continued receiving, raltegravir at the 400mg twice-daily dose. [8]
Viral efficacy remained similar between the two arms (78% vs 76% <50 copies/mL). Drug-related side effects were similar or less frequent in the raltegravir arm, as were grade 3/4 laboratory abnormalities (except pancreatic amylase (>2xULN: 2.5% vs 0) and creatinine kinase (10 xULN: 8.8% vs 2.6%). Lipid changes in combined raltegravir groups were not sgnificant for total cholesterol, LDL-cholesterol or triglycerides and HDL-cholesterol increased by a mean of +6.6 mg/dL (compared to +11.7 in the efavirenz arm). This meant that there was no significant difference in the total:HDL ratio between the two groups (-0.5 vs -0.4, p=0.451).
Comment
Although in a limited number of patients, this extended safety and efficacy data are encouraging.
To date, this more favourable lipid profile has not led to differences in body composition. A study presented at ICAAC as HTB went to press that we will report in full in the next issue showed similar DEXA results when compared to efavirenz at 48 weeks. [9]
Given that fat accumulation is one of the principal concerns for patients, and the mechanism is still unexplained, preliminary data should be made available for bone and body fat changes with all new drugs at the same time as other efficacy and safety data.
Ten years after lipodystrophy was identified as a major side effect, it is not acceptable to have wait for years after approval for these results.
However, another study at ICAAC reported encouraging data in respect to raltegravir activity in the CSF. [10]
Currently, access to raltegravir is imited for patients in the UK who could benefit from itÂ’s tolerability profile, due to the high cost.
References:
- Isentress (raltegravir) indication extended for the treatment of HIV-1 infection in treatment-naive patients. FDA announcement (08 July 2009).
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm171317.htm - CHMP poat-authorisation summary of postive opinion fro Isentress. (23 July 2009).
http://www.emea.europa.eu/pdfs/human/opinion/Isentress_47115109en.pdf - Lennox JL et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet 2009. Early online publication, 3 August 2009. doi:10.1016/S0140-6736(09)60918-1.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60918-1/abstract - Gotuzzo E et al. Sustained antiretroviral efficacy of raltegravir as part of combination ART in treatment-naive HIV-1 infected patients: 144-week data. 5th IAS 2009, Cape Town. Abstract MOPEB030.
http://www.ias2009.org/pag/Abstracts.aspx?AID=1895 - DeJesus E et al. Metabolic profiles and body composition changes in treatment-naive HIV-infected patients treated with raltegravir 400 mg bid-based vs. efavirenz 600 mg qhs-based combination therapy: 48-week data. 49th ICAAC, 12-15 September 2009, San Francisco. Abstract H-1571.
http://www.natap.org/2009/ICCAC/ICCAC_17.htm - Letendre S et al. Raltegravir concentrations in CSF exceed the median inhibitory concentration. 49th ICAAC, 12-15 September 2009, San Francisco. Abstract A1-1311.