Table 1.
Plasma Genotype by Single-Genome Sequencing
| Mutation Frequency (%)a | Genotype (Full-Length Integrase)b | Interpretation |
|---|---|---|
| Plasma genotype by SGS: sample collected on day 30 (2 d after first reactive HIV test and before ART start) | ||
| 19/24 (67) | L45Q, G59E, I72V, L101I, V201I, D270N | No INSTI resistance |
| 2/24 (8) | L45Q, G59E, I72V, L101I, Q148R, V201I, D270N | Q148R is a major INSTI resistance-associated mutationc |
| 1/24 (4) | L45Q, G59E, I72V, L101I, A128T, V201I, D270N | A128T is a nonpolymorphic INSTI accessory mutation |
| 1/24 (4) | L45Q, G59E, I72V, G94R, L101I, V201I, D270N | No INSTI resistance |
| 1/24 (4) | L45Q, G59E, W61*, I72V, L101I, V201I, D270N | Contains stop codon (*); likely nonviable virus |
| Plasma genotype by SGS: sample collected on day 42 (14 d after first reactive HIV test and 8 d after ART start) | ||
| 3/3 (100) | L45Q, G59E, I72V, L101I, V201I, D270N | No INSTI resistance |
Abbreviations: ART, antiretroviral therapy; CAB, cabotegravir; INSTI, integrase strand transfer inhibitor; RAM, resistance-associated mutation; SGS, single-genome sequencing.
aMutation frequency calculated as number of genomes with reported genotype as a proportion of number of genomes sequenced. From the day 30 sample, 24 genomes were sequenced, yielding a 90% certainty that a mutation present at 10% frequency would be detected. From the day 42 sample, 3 genomes were sequenced, yielding a 90% certainty that a mutation present at 50% frequency would be detected.
bMutations were defined using Stanford HIVDB, version 9.5.1, using an HXB2 subtype B reference. Major drug resistance-associated mutations are indicated in bold text, accessory mutations are indicated in underlined text, and integrase gene polymorphisms are indicated in black text.
cQ148R confers high-level resistance to cabotegravir and low-level resistance to dolutegravir and bictegravir. Although Q148R alone may not affect response to INSTIs used for first-line HIV treatment, intermediate or high-level INSTI resistance can occur when Q148R is present in combination with other INSTI RAMs (eg, if additional INSTI RAMs accumulate in the setting of cabotegravir exposure before HIV detection).