Effective 2-drug regimens may potentially decrease long-term exposure and toxicity associated with HIV-1 antiretroviral therapy (ART), according to study results presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI) held from March 8 to 11, 2020. Results further provided evidence to support the durability of 2-drug regimens against ART resistance.
In the primary analysis of the GEMINI-1 (ClinicalTrials.gov Identifier: NCT02831673) and GEMINI-2 (ClinicalTrials.gov Identifier: NCT02831764) studies (identically designed, multicenter, double-blind, randomized, noninferiority, phase 3 trials) at week 48, the 2-drug regimen of dolutegravir (DTG) + lamivudine (3TC) was shown to be noninferior to the 3-drug regimen of DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in people with HIV-1 who were ART naive. This led to the approval of the 2-drug regimen treatment strategy.
The researchers presented data from 11 participants who received a 2-drug regimen and 7 who received a 3-drug regimen with confirmed virologic withdrawal through week 96. Inclusion criteria included HIV-1 RNA viral loads falling in the range of 1000 to 500,000 copies/mL, HIV-1 genotype showed no major reverse transcriptase or protease resistance mutations, and demonstrating a negative hepatitis B virus infection test. Measures that were evaluated through the study course included baseline viral loads and CD4+ cell count characteristics, viral load progression, potential adherence issues, resistance, and study drug interruption.
The findings demonstrated that all patients with confirmed virologic withdrawal experienced virologic rebound and none had viral load blips (characterized as a single viral load between ≥50 and <200 copies/mL) that occurred before virologic withdrawal. Resistance analysis did not reveal any treatment-emergent genotypic or phenotypic resistance to integrase inhibitors or nucleoside reverse transcriptase inhibitors in any patients with confirmed virologic withdrawal in either treatment group. Overall, viral load progressions for patients with confirmed virologic withdrawal demonstrated a sharp increase followed by a reduction at the withdrawal visit, which is consistent with nonadherence/treatment interruption and ensuing re-adherence.
The study authors concluded that the 96-week data provide further evidence of the durability and high barrier to resistance of the 2-drug regimen of DTG + 3TC treatment strategy.
Underwood M, Wang R, Benson P, et al. DTG + 3TC vs DTG + TDF/FTC (GEMINI 1 & 2): confirmed virologic withdrawals through week 96. Poster presented at: CROI 2020; March 8-11, 2020. http://www.croiconference.org/sites/default/files/uploads/croi2020-boston-abstract-ebook.pdf. Accessed March 20, 2020.