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  IAS 2013: 7th IAS Conference on HIV
Pathogenesis Treatment and Prevention
June 30 - July 3 2013
Kuala Lumpur, Malaysia
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Maintenance Therapy With Raltegravir/Etravirine: Virologic Failure Rate 5% at 12 Months
  7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
Among 65 people who started maintenance therapy with raltegravir/etravirine during virologic suppression and continued treatment for at least 6 months, only 3 (4.6%) had a virologic rebound within 12 months, according to results of a single-center study in Paris [1]. Two of the three people with virologic failure had nonnucleoside-related mutations when they began raltegravir/etravirine, even though a nonnucleoside regimen had failed in none of these patients.
The nonnucleoside etravirine and the integrase inhibitor raltegravir have two potential advantages as maintenance-regimen components for people with lengthy antiretroviral histories--relatively benign toxicity profiles and low risk of interactions with other antiretrovirals. A maintenance regimen including only these two antiretrovirals would avert potential complications of continuing treatment with protease inhibitors (PIs) or nucleoside reverse transcriptase inhibitors (NRTIs). But both raltegravir and etravirine have low genetic barriers to resistance, so caution is warranted when giving them to people in whom other antiretrovirals have failed.
To assess the efficacy of raltegravir/etravirine without NRTIs in antiretroviral-experienced adults with virologic suppression and no nonnucleoside failures, clinical investigators at Pitie Salpetriere Hospital in Paris conducted this observational study of 91 people who switched to raltegravir/etravirine since January 2008. The primary endpoint was the proportion of people who maintained a viral load below 50 copies through 12 months of follow-up. The researchers defined virologic failure strictly as consecutive viral loads above 50 copies.
Median age of the study group stood at 53.6 (interquartile range [IQR] 48 to 57.8) and median treatment duration at 17.1 years (IQR 13 to 20.6). Study participants had taken a median of 10 previous regimens (IQR 6 to 13), and median time with a viral load below 200 copies before the switch stood at 4 years (IQR 2 to 7). People switched to raltegravir/etravirine because of lipodystrophy and/or dyslipidemia (21%), to simplify their regimen (10%), or because of renal toxicity (9%), digestive toxicity (9%), bone toxicity (7%), liver toxicity (6%), and neurologic toxicity (6%).
Among 91 people who switched to the two-drug regimen, 21 (23%) interrupted treatment, 3 because of virologic failure and 18 for other reasons, including 5 cases of side effects (5.5% of 91) possibly related to raltegravir or etravirine. Sixty-five people took raltegravir/etravirine for at least 6 months and 48 people took the combination for at least 12 months.
A per-protocol analysis of virologic success excluded people who stopped raltegravir/etravirine for reasons other than virologic failure. At the 6-month point, 55 of 56 people had maintained a viral load below 50 copies (98%, 95% confidence interval [CI] 90.5% to 99.6%). At the 12 month point, 36 of 39 people had kept their viral load below 50 copies (92%, 95% CI 79.6% to 97.3%).
Among the 3 people with study-defined virologic failure, one had a viral load of 90 copies at month 6 and a load of 38 copies at treatment discontinuation. The second had a viral load of 69 copies at month 3 and a load of 51 copies at discontinuation. And the third had a load of 2653 copies at month 6, 7697 copies at month 12, and 7679 copies at discontinuation.
Before the switch to raltegravir/etravirine, the first of these people had cumulative evidence of the V179I nonnucleoside mutation and the third person had evidence of K103N and Y181C--even though none of these people had a record of nonnucleoside failure. In this third patient, the nonnucleoside mutations P225H and Y181C and the integrase inhibitor mutation N155H emerged during virologic failure. In the second patient the V72I nonnucleoside mutation emerged.
The Paris team concluded that maintenance therapy with raltegravir/etravirine "represents a potentially safe NRTI/PI-sparing strategy in virologically suppressed patients with sensitive [HIV] strains." They cautioned that "before switching clinicians should check for potential prior resistance to NNRTIs." The investigators are conducting a larger prospective study to assess long-term virologic response and safety of this maintenance regimen.
1. Calin R, Valantin MA, 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 IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract WEPE516.