MONTREAL — A simplified treatment for maintenance of suppression of HIV infection stayed non-inferior to standard combination antiretroviral therapy (cART), a researcher reported.
After 144 weeks of treatment, 88% of 93 patients signed up for the SIMPL’HIV study who have been taking dolutegravir (Tivicay) plus emtricitabine (Emtriva) maintained HIV suppression to undetectable levels utilizing the 50 copies/ml assay versus 84% of 93 on cART, reported Annalisa Marinosci, MD, of the University of Geneva.
“Dolutegravir plus emtricitabine remains safe and non-inferior to standard care in the maintenance of viral suppression in adults with HIV-1 at 144 weeks,” she said in a presentation at the International AIDS Conference (IAC). “No new safety signals were observed and change [in] weight was similar between groups.”
In another IAC study, researchers shared results from the NAMSAL trial in Cameroon that compared dolutegravir (DTG) versus low-dose efavirenz (EFV400) as first-line ART in Cameroon.
In 2019, the planet Health Organization (WHO) recommended DTG as a preferred HIV treatment in every populations. That same year, the FDA approved the first two-drug complete regimen (DTG-lamivudine [Dovato]) for HIV-infected patients who’ve never received ART. In 2020, the agency approved DTG for the treating HIV-1 in select pediatric patients.
IAC session moderator Chloe Orkin, MD, MBChB, of Queen Mary University of London, told MedPage Today that “these studies give us reassurance that the planet Health Organization decision in suggesting usage of dolutegravir over efavirenz is prosperous over the longterm. “
“Dual-therapy regimens have grown to be an appropriate option to standard combination antiretroviral therapy to lessen toxicity, and costs and improve tolerability, adherence, and standard of living,” Marinosci said.
Marinosci and colleagues reported positive 48-week results from SIMPL-HIV in 2020 in PLOS Medicine. The analysis is really a multicenter, open-label, non-inferiority randomized trial among treatment-experienced people who have HIV in Switzerland. At baseline, patients with HIV-RNA <50 copies/ml for at the very least 24 weeks were randomized to switching to DTG-emtricitabine (FTC) or continuing cART. In addition they were randomized to a lower life expectancy biological and medical surveillance versus continuation of standard 3-monthly monitoring. Trial patients were about age 48 at baseline, while about 16% were women; 74% were white while 12% were Black. The median time that patients have been on cART was >7 years.
Marinosci reported that there have been no significant baseline differences in CD4-positive cells counts or in the lipid profile of the participant in the trial, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Similarly there is no difference between your groups in sugar levels after three years of treatment.
The trial’s main endpoint was the proportion of patients who maintained HIV-1 RNA <100 copies/mL throughout 144 weeks. During the period of the trial, five patients in the DTG-FTC arm were lost to follow-up as were eight patients in the cART arm, she said.
Mean CD4 gain between baseline and week 144 was 8.4 and 34.7 cell/mm3 with DTG-FTC and cART, respectively, for a -19.4 adjusted difference (95% CI -74.2 to 35.4), the authors reported.
In addition they discovered that, through 144 weeks, three participants in the DTG-FTC arm and six in the cART arm had HIV-RNA levels >100 copies/ml having an adjusted difference of -3.1% (95% CI -9.2-3 3.1%) in the intention-to-treat (ITT) population.
At week 144, HIV-RNA was >50 copies/ml in a single patient in the DTG-FTC group and four patients in the cART group, for a -3.2% adjusted difference (95% CI -7.7 to at least one 1.5%).
Weight gain was similar for women and men in both trial arms (about 5 lbs), Marinosci said, while a quality-of-life assessment was struggling to discern an improvement between your two trial arms.
Serious adverse events (AE) were observed in six patients on DTG-FTC and four patients on cART through the extended trial period, but Marinosci reported that no patients in either arms discontinued treatment because of any AE.
In 2019, the NAMSAL ANRS 12313 Study Group shared results from the trial having an 400-mg EFV-based regimen pitched against a DTG-based, reporting that the latter was non-inferior to the former reference regimen when it comes to viral suppression at week 48. “Among participants who had a viral load of at the very least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression,” they wrote in the New England Journal of Medicine (NEJM).
In the IAC presentation, Mireille Mpoudi Ngole-Etame, MD, MPH, of ANRS-Cameroon in Yaounde, detailed long-term outcomes from the trial in 610 patients. Her group discovered that at week 192, the proportion of participants with a viral load <50 copies/mL in ITT was 69% in the DTG group and 62% in the EFV400 group, for a 7.3% difference (95%CI -0.20;14.83, P=0.057). Also, the the per-protocol results were 75% in the DTG group and 66% in the EFV400 group for a 9.1% difference (95% CI 1.13;17.07, P=0.027).
Through the 4-year follow-up, there have been two new virological failures, as defined by WHO, without related resistance mutations in the DTG group and three in the the EFV400. There also were 13 and 11 new severe AEs seen, respectively.
With regards to weight gain over 4 years, there is significant more excess weight gain with the DTG-based regimen versus the EFV400-based regimen:
- Median weight gain +8.0 kg (about 18 lbs) in the DTG group vs +5.0 kg in the EFV400 group among women; +6.0 kg vs +4.0 kg among men
- Obesity incidence: 17% vs 11%; 26% vs 4%
- Proportion of patients who had a weight-gain of at the very least 15% in comparison to their initial weight: 43% vs 31%; 23% vs 25%
“Overall, both dolutegravir-based and low dose efavirenz-based regimens have durable safety for used in treatment-nave patients with HIV-1,” she stated. In the NEJM article, the authors noted that “a substantial increase in bodyweight…[has]…been connected with dolutegravir use…Follow-up of the participants will undoubtedly be critical, given the potentially important public health consequences that could jeopardize the large-scale usage of dolutegravir.”
Ed Susman is really a freelance medical writer located in Fort Pierce, Florida, USA.
Marinosci and Ngole-Etame disclosed no relationships with industry.
Orkin disclosed multiple relationships with industry including Merck, Bristol Myers Squibb, and Gilead.