![]() Exclusion criteria included presence of pre-existing major viral resistance mutations to NRTIs, non-NRTIs, or PIs 18 and active Centers for Disease Control and Prevention stage 3 HIV disease 19 (except for cutaneous Kaposi sarcoma and CD4 + cell count 100,000 copies/mL) and screening CD4 + cell count (≤200 or >200 cells/mm 3) and treated in a double-blind randomized phase from day 1 to week 96 during which lamivudine and tenofovir disoproxil fumarate/emtricitabine tablets were provided overencapsulated to visually match each other, followed by an open-label randomized phase from week 96 to 148. Women of reproductive potential were eligible if they were not pregnant or lactating and using highly effective contraception (defined by study protocol). Here, we report longer-term results from the GEMINI-1 and GEMINI-2 planned secondary analyses at 96 weeks.Įligible participants were aged ≥18 years with HIV-1 infection, ≤10 days of previous antiretroviral therapy (ART), and screening plasma HIV- to 500,000 copies/mL. Both guidelines indicated the need for longer-term data to support the use of dolutegravir + lamivudine in a broader patient population. 16 European AIDS Clinical Society guidelines also indicate that when preferred regimens are not feasible or available, 17 dolutegravir + lamivudine can be used. 14, 15 In addition, the 2019 update to the US Department of Health and Human Services treatment guidelines for HIV-1 infection supports the use of dolutegravir + lamivudine as initial treatment in patients for whom abacavir, tenofovir disoproxil fumarate, or tenofovir alafenamide either cannot be used or are not optimal. These data led to the approval of the fixed-dose combination of dolutegravir/lamivudine as a once-daily, single-tablet 2DR by the FDA and the European Medicines Agency. 13 Importantly, resistance mutations associated with INSTIs or NRTIs did not emerge in the few participants who had virologic failure. 11, 12 In primary week 48 analyses of the 2 phase III studies GEMINI-1 and GEMINI-2 in treatment-naive adults, dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL according to the US Food and Drug Administration (FDA) Snapshot algorithm. The integrase strand transfer inhibitor (INSTI) dolutegravir has a high barrier to resistance, making it a well-suited candidate for inclusion in a 2DR, 9 particularly when paired with lamivudine, 10 as previously observed. ![]() 7, 8 Thus, a need remains for well-tolerated, potent 2DRs with a high barrier to resistance. 2– 6 Although noninferior efficacy was shown against 3-drug regimens (3DRs), PIs are associated with adverse metabolic effects, long-term toxicities, and drug–drug interactions, limiting their appeal as components of lifelong therapy. 1 As such, early studies investigating 2DRs as initial or maintenance therapy for HIV infection evaluated the pairing of the potent, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI) lamivudine with pharmacologically boosted protease inhibitors (PIs), which have a high barrier to resistance. 1 The core antiretroviral agent in a 2DR must have high potency and a high barrier to resistance. Two-drug regimens (2DRs) can potentially reduce long-term cumulative drug exposure and decrease treatment-associated costs for HIV-1–infected individuals, who require lifelong therapy. Renal and bone biomarker changes favored dolutegravir + lamivudine. Dolutegravir + lamivudine had a lower rate of drug-related adverse events than dolutegravir + tenofovir disoproxil fumarate/emtricitabine (19.6% vs 25.0% relative risk ratio, 0.78 95% CI: 0.64 to 0.95). ![]() Eleven participants taking dolutegravir + lamivudine and 7 taking dolutegravir + tenofovir disoproxil fumarate/emtricitabine met confirmed virologic withdrawal criteria through week 96 none had treatment-emergent resistance mutations. Proportions of participants in the HIV-1 RNA ≥50 copies/mL Snapshot category were largely unchanged from week 48 to 96. At week 96, dolutegravir + lamivudine (N = 716) was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (N = 717) in achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm −10% noninferiority margin) in the pooled analysis (proportion of responders, 86.0% vs 89.5%, respectively adjusted treatment difference, −3.4% ), GEMINI-1 (−4.9% ), and GEMINI-2 (−1.8% ).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |