Cells producing residual viremia during antiretroviral treatment appear to contribute to rebound viremia following interruption of treatment
Fig 2
Clinical, antiretroviral treatment and phylogenetic tree for Participant 2.
Plasma HIV RNA values (red), CD4+ (blue), and CD8+ (green) T-cell counts, antiretroviral treatment (x-axis) and phylogenetic analyses are shown in separate panels (A,B). Plasma HIV RNA symbols are filled when HIV RNA was detected and are open circles when below the lower-limit-of-quantification (either 40 or 50c/mL, depending on clinical assay employed). Timepoints selected for C2V5env sequencing from plasma have viral load symbols encircled in black, with the QVOA timepoint indicated by a black arrow. Antiretroviral treatments and time intervals prescribed are shown by horizontal bars at the bottom. The durations of self-initiated ART-interruptions are indicated by black arrows at top of each panel. Maximum likelihood phylogenetic trees were rooted with the consensus sequence of each participant’s predicted founder virus (consensus sequence of 1st pre-ART timepoint). The key indicates the color code for the timepoints that specimens were collected relative to the estimated date of HIV infection, the antiretroviral treatment status, and the number of sequences derived from plasma or QVOA. Viral sequences from each unique QVOA well are represented by different symbols. Identical sequences are shown laterally and boxed for clarity. Significantly G-A hypermutated sequences are noted by #. CXCR4 and dual-tropic (R5X4 and X4) sequences are noted by *. Remaining sequences are predicted to be CCR5 (R5)-tropic. Residual viremia (RV) sequences identical to sequences from pre-ART plasma, viruses induced from QVOA cultures, or ART-interruption are shown with a horizontal black arrow. Clades with bootstrap values >70 are shown. Abbreviations: ARV: antiretroviral; AZT: zidovudine; DDI: didanosine; EFV: efavirenz; FTC: emtricitabine; 3TC: lamivudine; IDV: indinavir; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; RLP: rilpivirine; D4T: stavudine; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil.