The antiretroviral (ARV) regimens Tivicay (dolutegravir) plus Truvada (tenofovir disoproxil fumarate/emtricitabine) and Tivicay plus Descovy (tenofovir alafenamide/emtricitabine) suppressed HIV as effectively as Atripla (efavirenz/tenofovir disoproxil fumarate/emtricitabine) after the first year of an ongoing 96-week study.
The regimens that included Tivicay, however, especially when combined with Descovy, were associated with greater weight gain, especially among women.
At the 10th International AIDS Society Conference on HIV Science in Mexico City (IAS 2019), François Venter, MD, of the University of Witwatersrand in Johannesburg presented findings from an open-label randomized trial comparing the three regimens. The study was also published in The New England Journal of Medicine.
To participate in the study, people with HIV needed to be at least 12 years old, not have taken ARVs during the previous 30 days, have a creatinine clearance greater than 60 milliliters per minute or greater than 80 ml per minute if younger than 19 years old (indicating good kidney function) and have a viral load greater than 500. They could not be pregnant or have tuberculosis. The study did not screen participants for drug resistance, which is consistent with South African treatment guidelines.
A total of 1,053 people were enrolled in the study between February 2017 and May 2018. Fifty-nine percent were female. They had a median age of 32 years old. The average CD4 count was 336.
The participants were randomized into three even groups of 351 people to receive one of the three regimens, Tivicay plus Truvada, Tivicay plus Descovy, or Atripla. After 48 weeks, a respective 85% (298 people), 84% (294 people) and 79% (276) of the members of each group had a viral load below 50. These findings indicated that the two regimens based on Tivicay were as effective as, or noninferior to, Atripla.
More than 70% of those who had a viral load above 50 ultimately re-suppressed HIV after receiving adherence counseling and retesting.
None of the participants developed resistance to Tivicay.
One person in the Tivicay plus Descovy group and 10 people in the Atripla group discontinued treatment because of adverse health events. More people in the Atripla group discontinued treatment for other reasons.
Adverse events and laboratory abnormalities were similar across the three study arms. Between 5% and 7% experienced serious adverse health events. Between 12% and 24% had severe (Grade 3 and 4) adverse events, and between 63% and 72% had drug-related adverse events of any grade. One person died in the Tivicay plus Descovy group, as did one person in the Tivicay plus Truvada group and two people in the Atripla group.
Treatment had less of an impact on bone density and kidney function among those receiving Descovy compared with those receiving the other two regimens. There were no differences in sleep problems, anxiety or depression, which have been associated with the efavirenz component of Atripla.
The greatest weight gain was among those receiving Tivicay plus Descovy, underlining an increasing finding that Tivicay is associated with weight gain. While the tenofovir alafenamide (TAF) component of Descovy may be associated with better bone and kidney parameters compared with the tenofovir disoproxil fumarate (TDF) component of Truvada and Atripla, TAF also appears to be associated with greater weight gain. Among the men, the average weight gain after 96 weeks was 5 kilograms (11.0 pounds) in the Tivicay plus Descovy group, 4 kg (8.8 pounds) in the Tivicay plus Truvada group and 1 kg (2.2 pounds) in the Atripla group. Among the women, the average weight gain by that point was 10 kg (22.1 pounds), 5 kg (11.0 pounds) and 3 kg (6.6 pounds), respectively.
Venter noted that while there is a push to use Tivicay in lower- and middle-income countries, alternatives for people who gain weight will be needed.
To read the study abstract, click here.