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Pilot Study Finds Good 24-Week Response to First-Line Dolutegravir/3TC
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15th European AIDS Conference, October 21-24, 2015, Barcelona
Mark Mascolini
All 20 antiretroviral-naive people who started a stripped-down regimen of dolutegravir plus lamivudine (3TC) had a viral load below 50 copies by week 12, and that response lasted through week 24 [1]. The viral decay rate was similar to that seen in the SINGLE trial of dolutegravir plus abacavir/3TC.
Researchers at Fundacion HUESPED in Buenos Aires conducted the PADDLE trial to assess the efficacy, safety, and tolerability of the integrase inhibitor dolutegravir plus 3TC in previously untreated people [2]. All participants were 18 or older, had a viral load between 5000 and 100,000 copies, and had a CD4 count at or above 200. No one tested positive for hepatitis B surface antigen. The investigators enrolled 10 people who began 50/300 mg of once-daily dolutegravir/3TC then another 10 when they confirmed success in the first group.
The primary endpoint is the proportion of participants with a viral load below 50 copies at week 48 by the FDA snapshot analysis. This report offered a prespecified week-24 analysis. The researchers planned to stop the trial if more than 2 of 10 participants failed to have at least a 10-fold viral load drop at week 8. Participants stop treatment if they do not attain that goal or if they have (1) a viral load at or above 1000 copies at week 12, (2) a viral load at or above 400 copies at week 24, or (3) a confirmed rebound above 200 copies after reaching a sub-50-copy load.
Nineteen of 20 participants were men and median age stood at 34 years. Median viral load measured 24,128 copies and median CD4 count 507. After 2 weeks viral load dropped by an average 2.54 log (about 350-fold), a rate similar to that observed in the 3-drug SINGLE trial [3]. After 8 weeks of dolutegravir/3TC, all 20 study participants had a viral load below 50 copies. All 20 maintained a load below 50 copies through week 24. CD4 counts rose by an average 194 cells by week 12 and by 204 cells by week 24.
All adverse events reported through 24 weeks were grade 1, except for one grade 2 headache. All adverse events arose in the first week of therapy. No serious adverse events developed through 24 weeks, and no grade 3 or 4 lab abnormalities occurred.
PADDLE investigators itemized several limitations of their study, including its small size, single arm, and low pretreatment median viral load. Follow-up will continue through 96 weeks. The researchers noted that a randomized, fully powered trial must confirm these preliminary results.
References
1. Figueroa MI, Sued O, Patterson P, Gun A, Rolon MJ, Cahn P. Dolutegravir-lamivudine as initial therapy in HIV-infected, ARV naive patients: first results of the PADDLE trial. 15th European AIDS Conference, October 21-24, 2015, Barcelona. Abstract LBPS4/1.
2. ClinicalTrials.gov. Dolutegravir-lamivudine as dual therapy in naive HIV-infected patients: a pilot study (PADDLE). ClinicalTrials.gov identifier NCT02211482. https://clinicaltrials.gov/ct2/show/NCT02211482
3. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369:1807-1818.
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