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Viral Decay Similar With 2- and 3-Drug Dolutegravir Regimens
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HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow
Mark Mascolini
Viral decay--the rate at which HIV RNA disappears from plasma after antiretroviral therapy starts--proved equivalent with 2- and 3-drug regimens including the integrase inhibitor dolutegravir (DTG) [1]. The comparison included people with pretreatment viral loads up to 500,000 copies.
GEMINI-1 and -2 trials demonstrated that DTG plus lamivudine (3TC) is virologically noninferior to DTG plus TDF/FTC in previously untreated people with initial viral loads between 1000 and 500,000 copies [2]. Given good results with this simple 2-drug combination in GEMINI-1 and 2 and other trials [3], clinicians are keen to learn whether rapidity of viral suppression with DTG/3TC is similar to viral decay with standard 3-drug regimens. Faster decay means lower risk of HIV transmission or emergence of resistant HIV. Previous work showed similar viral decay with DTG/3TC in the PADDLE trial and with 3-drug DTG regimens in SPRING-1 and SINGLE [4]. But that analysis is limited by the small PADDLE population (16 people) and exclusion of people with a pretreatment load above 100,000 copies.
The new study involved participants in ACTG A5353, a single-arm study of DTG/3TC (50/300 mg once daily) in 120 antiretroviral-naive people, 31% of them with a pretreatment viral load above 100,000 copies. That trial found that 90% of participants had a week-24 viral load below 50 copies, with no difference between pretreatment viral load brackets [5].
Researchers compared viral load changes in ACTG A5353 with changes in trials of people taking DTG with 2 nucleosides, SPRING-1 (51 participants) and SINGLE (417 participants). They compared change from baseline viral load to levels at weeks 2, 4, 8, 12, 16, and 24.
The Wilcoxon Rank Sum test for noninferiority determined that viral decay with DTG/3TC was noninferior to decay with 3-drug DTG regimens at weeks 2, 4, 8, 12, 16, and 24 (P < 0.001 for all weeks). At weeks 2, 12, and 24, viral load dropped 2.52, 2.91, and 2.89 log10 copies with DTG/3TC and 2.46, 3.00, and 3.02 log10 copies with DTG plus two nucleosides.
The viral decay model determined that initial decay was faster with 2 than with 3 drugs, but that faster decay was partially offset when pretreatment viral load lay above 100,000 copies. Simple slope decay rates for participants in the 3 trials were:
-- A5353, initial viral load at or below 100,000 (n = 83): 1.272
-- A5353, initial viral load above 100,000 (n = 37): 0.725
-- SPRING and SINGLE, initial viral load at or below 100,000 (n = 321): 0.969
-- SPRING and SINGLE, initial viral load above 100,000 (n = 146): 0.596
The researchers noted that ACTG A5353 had a cap of 500,000 copies for pretreatment viral load, whereas the 2 comparison trials had no such cap. With that caveat in mind, they concluded that viral decay through 24 weeks is comparable with 2- and 3-drug dolutegravir regimens, even in people with pretreatment loads up to 500,000 copies.
References
1. Gillman J, Janulis P, Gulick R, et al. Comparable viral decay with dolutegravir plus lamivudine versus dolutegravir-based triple therapy. HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow. Abstract O213.
2. Cahn P, Madero JS, Arribas J, et al. Non-inferior efficacy of dolutegravir (DTG) plus lamivudine (3TC) versus DTG plus tenofovir/emtricitabine (TDF/FTC) fixed-dose combination in antiretroviral treatment-naive adults with HIV-1 infection: 48-week results from the GEMINI studies. AIDS 2018: 22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018. Abstract TUAB0106LB. http://www.natap.org/2018/IAC/IAC_12.htm
3. Taiwo BO, Marconi VC, Berzins B, et al. Dolutegravir plus lamivudine maintain HIV-1 suppression through week 48 in a pilot randomized trial. Clin Infect Dis. 2018;66:1794-1797. https://academic.oup.com/cid/article-abstract/66/11/1794/4775007
4. Sued OG, Figueroa MI, Rolon MJ, et al. Comparable viral decay in dual and triple dolutegravir-based antiretroviral therapy. Conference on Retroviruses and Opportunistic Infections (CROI). February 22-25, 2016, Boston, Abstract 947. http://www.croiconference.org/sessions/comparable-viral-decay-dual-and-triple-dolutegravir-based-antiretroviral-therapy
5. Taiwo BO, Zheng L, Stefanescu A, et al. ACTG A5353: a pilot study of dolutegravir plus lamivudine for initial treatment of human immunodeficiency virus-1 (HIV-1)-infected participants with HIV-1 RNA <500000 copies/mL. Clin Infect Dis. 2018;66:1689-1697.
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