Table 2.
Possible correlation between INSTI dissociation half-life (T1/2) and resistance.
| INSTIs | Dissociative T1/2 (h) |
Possible Integration Events Involving uDNA (2-LTR Circles or Linear Viral DNA) | Emergence of Resistant Strains with Mutations in the IN Gene | Emergence of Resistant Strains without Mutations in the IN gene |
|---|---|---|---|---|
| RAL | 8.8 [45] | ++ | + | − |
| EVG | 2.7 [45] | ++ | + | − |
| DTG | 71 [45] | +/− | +/− | + |
| BIC | 163 [46] | +/− | +/− | + |
When dissociation half-time is weak, in the case of RAL and EVG (two first lines), some integration events can occur involving uDNA when the INSTI is dissociated from the IN/DNA complex. Integrated DNA can produce infectious viral particles infecting new cells. New infections can lead to mutations in the integrase gene during the reverse-transcription step conferring resistance to INSTI. Propagation of the virus leads to the emergence of resistant strains. When the dissociation half-time is longer, as in the case of DTG or BIC (third and fourth lines), the IN/DNA complex is locked and no integration can occur. The only way to sustain the viral information is the weak replication from uDNA. As described previously, a weak amount of infectious viruses can be produced from uDNA leading to the infection of new cells. During the reverse transcription step, mutations, outside the integrase gene, can be selected conferring an advantage for the virus for its replication involving uDNA.