Table 1.
Case 1-2-3. On the left: major resistance mutations according to Stanford HIVDb version 9.0 (last updated on 2021-02-22) detected on plasma HIV-RNA and peripheral blood mononuclear cell (PBMC) HIV-DNA, cumulative (all the available tests, baseline included) versus baseline (test collected just before ibalizumab plus Optimized Background Therapy starting). NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; InSTI, Integrase strand transfer inhibitor; FPR, false positive rate; PDVF, protocol-defined virological failure; na, not available.
| Class | Sample, time | Major resistance mutations | Drug | Cumulative | Baseline | Plasma HIV-RNA | PBMC HIV-DNA | ||
|---|---|---|---|---|---|---|---|---|---|
| Case 1 | NRTI | Plasma HIV-RNA, historical | D67N, K70E, L74IL, Y115F, Q151M, M184MV, K219EK | ABC | High-Level | High-Level | High-Level | na | RESISTANCE PREDICTION |
| PBMC HIV-DNA, historical | na | FTC | High-Level | High-Level | High-Level | na | |||
| Plasma HIV-RNA, baseline | D67N, K70E, Y115F, Q151M, M184V | 3TC | High-Level | High-Level | High-Level | na | |||
| PBMC HIV-DNA, baseline | na | TDF/TAF | High-Level | High-Level | High-Level | na | |||
| NNRTI | Plasma HIV-RNA, historical | L100IL, G190Q, F227L | DOR | High-Level | High-Level | High-Level | na | ||
| PBMC HIV-DNA, historical | na | EFV | High-Level | High-Level | High-Level | na | |||
| Plasma HIV-RNA, baseline | L100IL, V106AV, G190Q, F227FL | ETR | High-Level | High-Level | High-Level | na | |||
| PBMC HIV-DNA, baseline | na | NVP | High-Level | High-Level | High-Level | na | |||
| RPV | High-Level | High-Level | High-Level | na | |||||
| PI | Plasma HIV-RNA, historical | M46L, I50V, V82AS, L90M | ATV/r | High-Level | High-Level | High-Level | na | ||
| PBMC HIV-DNA, historical | na | DRV/r | Intermediate | Intermediate | Intermediate | na | |||
| Plasma HIV-RNA, baseline | V32I, M46L, I50V, V82A, L90M | LPV/r | High-Level | High-Level | High-Level | na | |||
| PBMC HIV-DNA, baseline | na | TPV/r | Potential Low-Level | Potential Low-Level | Potential Low-Level | na | |||
| InSTI | Plasma HIV-RNA, historical | E138K, G140S, Y143CRHY, Q148H | BIC | High-Level | High-Level | High-Level | High-Level | ||
| PBMC HIV-DNA, historical | E138EK, G140GS, Y143YCHR, Q148QH | DTG | High-Level | High-Level | High-Level | High-Level | |||
| Plasma HIV-RNA, baseline | E138K, G140S, Y143R, Q148H | EVG | High-Level | High-Level | High-Level | High-Level | |||
| PBMC HIV-DNA, baseline | E138EK, G140GS, Y143YCHR, Q148QH | RAL | High-Level | High-Level | High-Level | High-Level | |||
| Entry Inhibitors | Plasma HIV-RNA, historical | CXCR4 (range FPR 0·2-6·7%); gp41: no mutations | MVC | Not effective | Not effective | Not effective | Not effective | ||
| PBMC HIV-DNA, historical | CXCR4 (FPR 1·7%); gp41: no mutations | ||||||||
| Plasma HIV-RNA, baseline | CXCR4 (FPR 1·7%); gp41: na | ENF | Susceptible | na | Susceptible | Susceptible | |||
| PBMC HIV-DNA, baseline | CXCR4 (FPR 1·7%); gp 41: na | ||||||||
| Plasma HIV-RNA, BRIGHTE baseline | no mutations | FTR | Reduced susceptibility to TMRa | na | Reduced susceptibility to TMRa | na | |||
| Plasma HIV-RNA, BRIGHTE PDVF | M426M/L | ||||||||
| Case 2 | NRTI | Plasma HIV-RNA, historical | M41L, D67N, K70Q, M184I, L210W, T215Y, K219R | ABC | High-Level | High-Level | High-Level | High-Level | RESISTANCE PREDICTION |
| PBMC HIV-DNA, historical | M41L, D67N, K70Q, M184I, L210W, T215Y, K219R | FTC | High-Level | High-Level | High-Level | High-Level | |||
| Plasma HIV-RNA, baseline | M41L, D67N, K70Q, M184I, L210W, T215Y, K219R | 3TC | High-Level | High-Level | High-Level | High-Level | |||
| PBMC HIV-DNA, baseline | M41L, D67N, K70Q, M184I, L210W, T215Y, K219R | TDF/TAF | High-Level | High-Level | High-Level | High-Level | |||
| NNRTI | Plasma HIV-RNA, historical | K101KE, Y181V, G190A | DOR | Intermediate | Susceptible | Intermediate | Susceptible | ||
| PBMC HIV-DNA, historical | G190A | EFV | High-Level | Intermediate | High-Level | Intermediate | |||
| Plasma HIV-RNA, baseline | G190A | ETR | High-Level | Potential Low-Level | High-Level | Potential Low-Level | |||
| PBMC HIV-DNA, baseline | G190A | NVP | High-Level | High-Level | High-Level | High-Level | |||
| RPV | High-Level | Low-Level | High-Level | Low-Level | |||||
| PI | Plasma HIV-RNA, historical | V32I, M46L, I54A, I84V, L90M | ATV/r | High-Level | High-Level | High-Level | High-Level | ||
| PBMC HIV-DNA, historical | V32I, M46L, I54A, I84V, L90M | DRV/r | Intermediate | Intermediate | Intermediate | Intermediate | |||
| Plasma HIV-RNA, baseline | V32I, M46L, I54A, I84V, L90M | LPV/r | High-Level | High-Level | High-Level | High-Level | |||
| PBMC HIV-DNA, baseline | V32I, M46L, I54A, I84V, L90M | TPV/r | High-Level | High-Level | High-Level | High-Level | |||
| InSTI | Plasma HIV-RNA, historical | E138A, G140S, Y143H, Q148H | BIC | High-Level | High-Level | High-Level | High-Level | ||
| PBMC HIV-DNA, historical | E138A, G140S, Q148H | DTG | High-Level | High-Level | High-Level | High-Level | |||
| Plasma HIV-RNA, baseline | E138A, G140S, Q148H | EVG | High-Level | High-Level | High-Level | High-Level | |||
| PBMC HIV-DNA, baseline | E138A, G140S, Q148H | RAL | High-Level | High-Level | High-Level | High-Level | |||
| Entry Inhibitors | Plasma HIV-RNA, historical | CXCR4 (range FPR 0·4-2·68%); gp41: G36E, L34M | MVC | Not effective | Not effective | Not effective | Not effective | ||
| PBMC HIV-DNA, historical | CXCR4 (FPR 5·8%); gp41: no mutations | ||||||||
| Plasma HIV-RNA, baseline | CCR5 (FPR 69·8%); gp41: no mutations | ENF | Potential resistance | Susceptible | Potential resistance | Susceptible | |||
| PBMC HIV-DNA, baseline | CXCR4 (FPR 3·1%); gp41: no mutations | ||||||||
| Plasma HIV-RNA, BRIGHTE baseline | no mutations | FTR | Reduced susceptibility to TMRb | na | Reduced susceptibility to TMRb | na | |||
| Plasma HIV-RNA, BRIGHTE PDVF | M426L | ||||||||
| Case 3 | NRTI | Plasma HIV-RNA, historical | M41L, D67N, T69Si, M184IMV, L210W, T215Y, K219EK | ABC | High-Level | Intermediate | High-Level | Intermediate | RESISTANCE PREDICTION |
| PBMC HIV-DNA, historical | M41L, D67N, L210W, T215H, K219E | FTC | High-Level | Susceptible | High-Level | Susceptible | |||
| Plasma HIV-RNA, baseline | M41L, D67N | 3TC | High-Level | Susceptible | High-Level | Susceptible | |||
| PBMC HIV-DNA, baseline | M41L, D67N, L210W, T215H, K219E | TDF/TAF | High-Level | Intermediate | High-Level | Intermediate | |||
| NNRTI | Plasma HIV-RNA, historical | L100IL, K103N | DOR | Intermediate | Intermediate | Intermediate | Intermediate | ||
| PBMC HIV-DNA, historical | L100IL, K103N | EFV | High-Level | High-Level | High-Level | High-Level | |||
| Plasma HIV-RNA, baseline | L100I, K103N | ETR | Intermediate | Intermediate | Intermediate | Intermediate | |||
| PBMC HIV-DNA, baseline | L100I, K103N | NVP | High-Level | High-Level | High-Level | High-Level | |||
| RPV | High-Level | High-Level | High-Level | High-Level | |||||
| PI | Plasma HIV-RNA, historical | M46L, I50V, V82A, L90M | ATV/r | High-Level | High-Level | High-Level | High-Level | ||
| PBMC HIV-DNA, historical | M46L, I50L, V82VA, L90M | DRV/r | Low-Level Resistance | Susceptible | Low-Level | Susceptible | |||
| Plasma HIV-RNA, baseline | M46L, I50L, L90M | LPV/r | High-Level | High-Level | High-Level | High-Level | |||
| PBMC HIV-DNA, baseline | M46L, I50L, V82VA, L90M | TPV/r | Susceptible | Susceptible | Susceptible | Susceptible | |||
| InSTI | Plasma HIV-RNA, historical | Y143CHRY, S147G, N155H | BIC | Intermediate | Intermediate | Intermediate | Intermediate | ||
| PBMC HIV-DNA, historical | S147G, N155H | DTG | Intermediate | Intermediate | Intermediate | Intermediate | |||
| Plasma HIV-RNA, baseline | none | EVG | High-Level | High-Level | High-Level | High-Level | |||
| PBMC HIV-DNA, baseline | S147G, N155H | RAL | High-Level | High-Level | High-Level | High-Level | |||
| Entry Inhibitors | Plasma HIV-RNA, historical | CCR5 (range FPR 50·5-87·8%); gp41: L34M | MVC | Not effective | Not effective | Susceptible | Not effective | ||
| PBMC HIV-DNA, historical | CXCR4 (FPR 1·8%); gp41: L34M | ||||||||
| Plasma HIV-RNA, baseline | CCR5 (FPR 86·2%); gp41: L34M | ENF | Susceptible | Susceptible | Susceptible | Susceptible | |||
| PBMC HIV-DNA, baseline | CXCR4 (FPR 1·8%); gp41: L34M | ||||||||
| Plasma HIV-RNA, BRIGHTE baseline | M426L | FTR | Reduced susceptibility to TMRc | na | Reduced susceptibility to TMRc | na | |||
| Plasma HIV-RNA, BRIGHTE PDVF | M426L |
On the right: resistance prediction according to Stanford HIVDb version 9.0 (last updated on 2021-02-22) for the drugs of common use for each class, distinguished based on time (cumulative plasma + PBMC GRTs versus baseline plasma + PBMC GRTs) and sample (cumulative plasma GRTs versus cumulative PBMC GRTs). ABC, abacavir; FTC, emtricitabine; 3TC, lamivudine; TDF/TAF, tenofovir disoproxil fumarate/tenofovir alafenamide; DOR, doravirine; EFV, efavirenz; ETR, etravirine; NVP, nevirapine; RPV, rilpivirine; ATV/r, atazanavir/ritonavir; DRV/r, darunavir/r; LPV/r, lopinavir/r; TPV/r, tipranavir/r; BIC, bictegravir; DTG, dolutegravir; EVG, elvitegravir; RAL, raltegravir; MRV, maraviroc; ENF, enfuvirtide. (a,b,c) Viral susceptibility to temsavir (TMR) at baseline and after PDVF was reported as fold change (FC) in half-maximal inhibitory concentration (IC50) and were (a) 0·37 and 17; (b) 7·56 and >4669·6; (c) 181 and 288, respectively.