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IAS 2013: Switch to Etravirine Maintains Viral Suppression and Improves Lipid Levels

People with HIV who switch from their current antiretroviral regimen to the NNRTI etravirine (Intelence) maintain undetectable viral load and may see improvement in metabolic parameters, according to a report presented at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) this week in Kuala Lumpur.

Modern antiretroviral therapy (ART) is highly safe and effective, but there is always room for refinement, including drugs that are easier to take or cause fewer side effects and long-term toxicities.

Lauren Bull and colleagues from Chelsea and Westminster Hospital in London evaluated long-term treatment outcomes among people who took ART regimens containing the second-generation non-nucleoside reverse transcriptase inhibitor(NNRTI) etravirine, most of whom switched drugs for reasons other than virological failure.

This retrospective case review included 389 people with HIVwho started a regimen of etravirine plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) between August 2008 and December 2012. Bull said the analysis included a mix of people taking etravirine once-daily and twice-daily.

Most patients (88%) were on a suppressive ART regimen with viral load below 50 copies/mL at the time of the switch. Among this group, the median CD4 count was high, at 505 cells/mm³. 

The remaining 44 patients had detectable viral load when they started etravirine. 20 were restarting ART after a treatment break, 13 switched due to efavirenz side effects before they became undetectable, 2 switched from protease inhibitor monotherapy, and 9 were treatment-naive. This group had a median viral load of approximately 44,000 copies/mL and a median CD4 count of 300 cells/mm³. Bull did not report the patients' gender, age, or racial/ethnic distribution.

Among people who changed therapy with suppressed viral load, nearly two-thirds (61%) switched from the Atripla (efavirenz/tenofovir/emtricitabine) coformulation, 11 switched from other efavirenz-based combinations, and 19% switched from protease inhibitor regimens.

The most common reason for switching -- reported by 246 patients -- was central nervous system (CNS) side effects of efavirenz. A variety of reasons motivated switches from protease inhibitors, including gastrointestinal symptoms and concern about cardiovascular risk and drug interactions.

Results

• At 6 months after switching to efavirenz, 99% of participants who started with suppressed virus maintained undetectable viral load.
• The number of patients remaining in the analysis dropped off over time -- falling to 136 people still being followed at 36 months and 39 people at 48 months -- but rates of viral suppression remained high, between 96% and 100%.
• CD4 counts rose over time, exceeding 650 cells/mm³ at years 3 and 4.
• Among those who started with detectable viral load, most -- including all the treatment-naive individuals -- achieved viral suppression by 6 months, and most maintained it through 36 months.
• 3 people who started etravirine with suppressed viral load experienced viral rebound and had detectable viral load when they stopped etravirine; 1 had a 181C etravirine resistance mutation and 1 developed NRTI resistance.
• 6 people in the group who started etravirine with detectable HIV had continued virological failure, all of whom were non-adherent to therapy; 4 patients developed etravirine resistance and 2 developed NRTI resistance
• 86 people who switched with suppressed virus stopped taking etravirine during the study period.
• The most common reason, reported by half, was CNS side effects.
• 31 people who had previously been on efavirenz stopped etravirine as well due to continuation of the same types of symptoms.
• 6 people stopped due to known or suspected drug interactions.
• Etravirine had a "favorable lipid profile," as seen in previous studies of treatment-naive individuals.
• Lipid levels declined after switching to etravirine, with significant decreases in total cholesterol, LDL ("bad cholesterol") and triglycerides. Although HDL ("good cholesterol") also fell slightly, the LDL:HDL ratio improved.

Based on these findings, the researchers concluded, "Etravirine is an alternative switch option in individuals with an undetectable viral load and intolerant of their current third agent."

Etravirine/raltegravir Maintenance Therapy

A related study reported in a poster at the conference found that a 2-drug regimen of etravirine plus the integrase inhibitor raltegravir (Isentress) kept viral load suppressed and was well-tolerated when used as maintenance therapy.

This observational analysis looked at 91 patients at Hôpital Pitié-Salpêtrièrein Paris who had viral load below 50 copies/mL when they switched to 200 mg twice-daily etravirine plus 400 mg twice-daily raltegravir from a standard ART regimen. Participants were highly treatment-experienced and had used a median of 10 prior regimens. The most common reasons for switching were to manage metabolic or kidney toxicity, to prevent toxicity, or to simplify treatment.

In a per-protocol analysis, 92% of patients still taking the dual regimen maintained HIV suppression at 12 months. However, 3 people experienced virological failure (HIV RNA >50 copies/mL), all of who had prior NNRTI exposure; 2 were found to have pre-existing mutations conferring resistance to etravirine.

"Dual therapy with raltegravir plus etravirine represents a potential virologically safe NRTI/PI-sparing option in suppressed patients with sensitive [HIV] strains," the researchers concluded.

7/6/13

References

L Bull, M Bower, an M Nelson. Long term therapeutic success of etravirine in switch and naive patients. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WEAB0105.

R Calin, MA Valantin, A Simon A, et al. Raltegravir/etravirine dual therapy as a virologically safe treatment option in suppressed HIV-1-infected patients without previous NNRTI failure. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WEPE516.