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Second-Line Therapies for HIV: Two Studies Whose Impact Will Last Well Beyond CROI 2013

By Josep M. Llibre, M.D., and Benjamin Young, M.D., Ph.D.

March 14, 2013

Several studies provided important advances in how to approach the treatment of individuals experiencing failure of first-line NNRTI-based treatment.

The SECOND LINE study (for which the poster presentation is available online) suggested that NRTIs might not be needed for second-line treatment. The study randomized 541 individuals failing NNRTI first-line treatment from 15 countries to receive either lopinavir/ritonavir (Kaletra) + two to three N(t)RTIs or the NRTI-sparing regimen of lopinavir/ritonavir + raltegravir (RAL, Isentress). The baseline CD4+ cell count of the participants was 190 cells/mm3 and 20% had a viral load greater than 100,000 copies/mL.

After 48 weeks, approximately 77% of the participants had virologic suppression below 50 copies/mL: 77.8% in the RAL arm vs. 76.8% in the 2/3 N(t)RTI arm (treatment difference 1.03% [95%CI: -6.04, +8.29]), therefore demonstrating the noninferiority of the nuke-sparing regimen. RAL recipients had significantly greater increases in CD4+ cell count (167 vs. 132 cells/mm3, P < .01).


Meanwhile, a phase 2 study showed superiority of the investigational integrase inhibitor dolutegravir (DTG) to RAL in second line treatment. The SAILING study (for which the poster is also available online) gave ART-experienced, integrase inhibitor-naive participants an optimized background regimen; participants were randomized to receive either RAL or DTG. Fifty percent of participants had three or more class drug resistance.

At a planned 24-week interim analysis performed after all participants reached week 48 of treatment, DTG was statistically superior to RAL, with 79% vs. 70% of participants achieving an undetectable viral load (treatment difference +9.7% [95%CI: 3.1, 15.9]). This difference (RAL vs. DTG) was driven by differences in adverse events (3% vs. 1%) and lack of efficacy (7% vs. 4%). There were fewer virologic failures and less detected drug resistance mutation in the DTG arm of the study. Actually, no participants developed phenotypic DTG resistance, while nine out of 10 participants failing RAL with genotypic data showed complete RAL resistance.

Which other studies presented at CROI 2013 will have lasting impact long after memories of the conference itself have faded? Read more of Dr. Llibre and Dr. Young's top picks.

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