N155H

N155H is a mutation in the HIV-1 integrase enzyme, involving a substitution of asparagine (N) with histidine (H) at residue 155. It is recognized as a primary resistance mutation associated with the use of integrase strand transfer inhibitors, particularly raltegravir.

The mutation occurs in the catalytic core domain of integrase and reduces the virus’s susceptibility to raltegravir by altering the enzyme’s interaction with the drug. Viruses carrying N155H often exhibit lower replication fitness in drug-free conditions, and the clinical impact can depend on the presence of additional mutations.

In treatment settings, N155H is frequently observed in patients failing raltegravir-containing regimens. On its own, it may confer modest resistance; when accompanied by secondary mutations such as those at residues 140, 148, or 155 itself in combination with other changes, resistance can become higher and cross-resistance to other integrase inhibitors can emerge.

Epidemiologically, N155H is more commonly reported in treatment-experienced individuals than in those who are integrase inhibitor–naive. It is monitored in resistance interpretation efforts and databases, where it is cited as a major mutation affecting raltegravir susceptibility and as a potential contributor to complex resistance patterns involving other integrase inhibitors.