Extended Data Fig. 4: Viral rebound, amino acid variants at 10-1074 contact sites and sensitivities of latent and rebound viruses in the participants with detectable viraemia (>20 copies per ml) two weeks before or at the start of ATI.
From: Combination therapy with anti-HIV-1 antibodies maintains viral suppression

a, Plasma HIV-1 RNA levels (black; left y axis) and bNAb serum concentrations (3BNC117, red; 10-1074, blue; right y axis). Red and blue triangles indicate 3BNC117 and 10-1074 infusions, respectively. Serum antibody concentrations were determined by TZM-bl assay. Grey-shaded areas indicate time on ART. Lower limit of detection of HIV-1 RNA was 20 copies per ml. b, Kaplan–Meier plots summarizing time to viral rebound. The y axis shows the percentage of participants that maintained viral suppression. The x axis shows the time in weeks after the start of ATI. Participants receiving the combination of 3BNC117 and 10-1074 are indicated by the blue line (n = 4). The dotted red line indicates a cohort of individuals receiving 3BNC117 alone during ATI9 (n = 13) and the dotted black line indicates a cohort of participants who underwent ATI without any intervention10 (n = 52). c, Colour charts show Env contact sites of 10-1074 at the G(D/N)IR motif (positions 324–327, according to HXB2 numbering) and the glycan at the potential N-linked glycosylation site at position 332 (NxS/T motif at positions 332–334). LR, latent reservoir viruses isolated by Q2VOA (week −2); RB, rebound viruses isolated by SGA (plasma) or viral outgrowth (PBMCs). Each amino acid is represented by a colour and the frequency of each amino acid is indicated by the height of the rectangle. Shaded rectangles indicate the lack of variation between latent reservoir and rebound viruses at the indicated position. Full-colour rectangles represent amino acid residues with changes in distribution between reservoir and rebound viruses. d, Dot plots showing the IC80 (μg ml−1) of 3BNC117 (left) and 10-1074 (right) against latent and rebound viruses determined by TZM-bl neutralization assay. Q2VOA-derived latent viruses from week −2 are shown as black circles. For outgrowth culture-derived rebound viruses, the highest IC80 determined is shown as red circle. For 9250 and 9253, no viruses could be obtained from rebound outgrowth cultures and pseudoviruses were made from env sequences of the latent reservoir (Q2VOA) and rebound viruses (plasma SGA). Note that 9249 and 9253 had pre-existing resistant viruses in the reservoir (IC50 > 2 μg ml−1). 9248 and 9250 had pre-existing viruses that failed to reach an IC100 when tested up to 50 μg ml−1 for 3BNC117 (Extended Data Fig. 5). Rebound viruses of all four participants had an IC80 or IC100 of >50 μg ml−1 for both 3BN117 and 10-1074.