Two to TANGO: Dolutegravir-lamivudine combo safe, effective substitute for TAF regimen
Individuals with HIV-1 who demonstrate virologic suppression on a tenofovir alafenamide fumarate (TAF)-based three- or four-drug regimen (TBR) could safely switch to a two-drug regimen comprising dolutegravir and lamivudine, according to results from the phase III TANGO* study presented at the recent International AIDS Society conference (IAS 2019).
“Switching to the fixed-dose combination of dolutegravir plus lamivudine was non-inferior to remaining on a TAF-based three- or four-drug regimen through 48 weeks in [antiretroviral therapy (ART)]-experienced, virologically suppressed adults,” said Dr Jean van Wyk, Global Medical Lead for dolutegravir, Viiv Healthcare, Brentford, UK, who presented the results.
Participants in this multicentre, open-label industry-sponsored trial were 741 HIV-1-positive individuals demonstrating virologic suppression (RNA <50 c/mL for >6 months) on stable TBR. They were randomized to receive dolutegravir (50 mg) plus lamivudine (300 mg) once/day (n=369, median age 40 years, 7 percent female) or continue with TBR (n=372, median age 39 years, 9 percent female) for 148 weeks.
Patients with previous virologic failure, NRTI or INSTI resistance, hepatitis B, or requiring treatment for hepatitis C were excluded.
At 48 weeks, a similar proportion of patients on dolutegravir-lamivudine and TBR maintained virologic suppression (93.2 percent vs 93.0 percent), with one patient on dolutegravir-lamivudine demonstrating a viral load of RNA ≥50 c/mL compared with two patients on TBR (adjusted difference, -0.3 percent, 95 percent confidence interval, -1.2 to 0.7). [IAS 2019, abstract WEAB0403LB]
None of the patients treated with dolutegravir-lamivudine experienced virologic withdrawal at 48 weeks, compared with one patient treated with TBR, and no patients on dolutegravir-lamivudine developed resistance.
Adverse event (AE) incidence was comparable between dolutegravir-lamivudine and TBR recipients (80 percent vs 79 percent). Frequently occurring AEs included nasopharyngitis (12 percent vs 11 percent), upper respiratory tract infection (8 percent vs 9 percent), diarrhoea (8 percent vs 7 percent), and back pain (6 percent vs 8 percent). Drug-related grade 2–5 AEs occurred at a low rate in dolutegravir-lamivudine and TBR recipients (5 percent vs 1 percent) as did AE-related study withdrawals (4 percent vs 1 percent).
There were significant between-group differences pertaining to certain renal and bone biomarkers. Patients on dolutegravir-lamivudine experienced a significantly greater increase in serum creatinine levels compared with TBR recipients (adjusted mean change, 6.67 vs 2.19 μmol/L) as well as a greater decrease in eGFR (from creatinine) levels (adjusted mean change, -7.8 vs -3.0 mL/min/1.73 m2; p<0.001 for both). Compared with TBR recipients, dolutegravir-lamivudine recipients demonstrated greater increases in serum procollagen 1 N-terminal propeptide (adjusted mean change, 9.3 vs 6.4 μg/L) and serum type 1 collagen C-telopeptide levels (adjusted mean change, 0.0602 vs 0.0310 μg/L; p<0.05 for both) and a decrease in serum osteocalcin levels (adjusted mean change, -1.15 vs 0.69 μg/L; p<0.001). However, it remains to be seen if these findings have any clinical significance, said van Wyk.
“New drugs and novel treatment regimens have the potential to improve long-term tolerability, reduce costs, and reduce the number of pills that people living with HIV … have to manage every day,” said IAS 2019 International Scientific Chair Dr Anton Pozniak from the Chelsea and Westminster Hospital NHS Trust, United Kingdom.
“Today when people start getting diagnosed with HIV, we expect them to go on therapy as soon as possible and then to remain on it for a lifetime and this can be decades, 40 years or longer. That’s why we believe it’s imperative to look at reducing cumulative long-term ART exposure,” said van Wyk.
“These data support the use of [dolutegravir-lamivudine] as a new robust switch option without an increased risk of virologic failure or resistance and with reduced ART exposure,” he said, highlighting that TANGO is an ongoing 3-year trial, and as such, long-term results will be revealed in due course.