Drug resistance mutations in patients infected with HIV-2 living in Spain

• Published in: Journal of antimicrobial chemotherapy Vol. 66; no. 7; pp. 1484 - 1488
• Main Authors: Treviño, Ana, de Mendoza, Carmen, Caballero, Estrella, Rodríguez, Carmen, Parra, Patricia, Benito, Rafael, Cabezas, Teresa, Roc, Lourdes, Aguilera, Antonio, Soriano, Vincent
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-07-2011; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Biological and medical sciences; Child; Child, Preschool; Drug resistance; Drug Resistance, Viral; Female; HIV; HIV Infections - virology; HIV Protease - genetics; HIV Reverse Transcriptase - genetics; HIV-2 - drug effects; HIV-2 - genetics; HIV-2 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Integrases - genetics; Male; Medical sciences; Middle Aged; Mutation; Mutation, Missense; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Genetic; Sequence Analysis, DNA; Spain; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Proteins - genetics; Young Adult; Europe; Spain; protease; reverse transcriptase; integrase; Human; Immunopathology; Treatment resistance; RNA-directed DNA polymerase; Enzyme; Transferases; Reverse transcription; Patient; AIDS; Immune deficiency; Infection; Peptidases; Nucleotidyltransferases; Viral disease; Hydrolases; Genetics; Mutation
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr164

Background
In contrast with HIV-1, information about drug resistance in HIV-2 is scarce and mainly derived from small series of patients failing antiretroviral therapy.
Methods
The spectrum of changes in the reverse transcriptase (RT), protease (PR) and integrase (INT) genes was examined in HIV-2 individuals enrolled in the HIV-2 Spanish register.
Results
From a total of 236 HIV-2-infected individuals registered in Spain from 1989 to June 2010, 53 PR, 44 RT and 8 INT sequences were obtained. Low plasma viraemia precluded collection of this information from most of the remaining cases. No major mutations associated with drug resistance in HIV-1 were recognized in 29 PR, 20 RT and 5 INT sequences from antiretroviral-naive HIV-2 individuals, although natural polymorphisms with potential effects on susceptibility to PR inhibitors were recognized at 10 positions (L10V/I, V32I, M36I, M46I, I47V, Q58E, A71V/I, G73A, V82I and L89I/V) and for nucleoside reverse transcriptase inhibitors at three positions (T69N, V75I and K219E). In 24 antiretroviral-experienced patients with virological failure the most frequent major RT resistance mutations were M184V (58%), Q151M (33%) and K65R (21%), which are rarely seen thymidine analogue mutations. In PR the most frequent major changes were V47A (17%), I54M (17%), I82F (13%), L90M (29%) and L99F (29%). Two of the three patients who failed on raltegravir had N155H in the INT region.
Conclusions
Drug resistance mutations in HIV-2 are selected at the same positions as in HIV-1, although with different frequency. Polymorphisms in the RT and PR associated with drug resistance in HIV-1 as compensatory changes are common in untreated HIV-2 subjects. These findings highlight the need for specific guidelines for interpreting genotypic resistance patterns in HIV-2 infection.