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.
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.
Authors: Robert A Smith; Dana N Raugi; Vincent H Wu; Sally S Leong; Kate M Parker; Mariah K Oakes; Papa Salif Sow; Selly Ba; Moussa Seydi; Geoffrey S Gottlieb Journal: Antimicrob Agents Chemother Date: 2015-09-21 Impact factor: 5.191
Authors: Nuno R Faria; Ioannis Hodges-Mameletzis; Joana C Silva; Berta Rodés; Smit Erasmus; Stefania Paolucci; Jean Ruelle; Danuta Pieniazek; Nuno Taveira; Ana Treviño; Maria F Gonçalves; Sabelle Jallow; Li Xu; Ricardo J Camacho; Vincent Soriano; Patrick Goubau; João D de Sousa; Anne-Mieke Vandamme; Marc A Suchard; Philippe Lemey Journal: J Gen Virol Date: 2011-12-21 Impact factor: 3.891
Authors: Vincent H Wu; Robert A Smith; Sara Masoum; Dana N Raugi; Selly Ba; Moussa Seydi; Jay A Grobler; Geoffrey S Gottlieb Journal: Antimicrob Agents Chemother Date: 2017-07-25 Impact factor: 5.191
Authors: Philip L Tzou; Diane Descamps; Soo-Yon Rhee; Dana N Raugi; Charlotte Charpentier; Nuno Taveira; Robert A Smith; Vicente Soriano; Carmen de Mendoza; Susan P Holmes; Geoffrey S Gottlieb; Robert W Shafer Journal: J Infect Dis Date: 2020-06-11 Impact factor: 5.226
Authors: Robert A Smith; Dana N Raugi; Charlotte Pan; Matthew Coyne; Alexandra Hernandez; Brad Church; Kara Parker; James I Mullins; Papa Salif Sow; Geoffrey S Gottlieb Journal: PLoS One Date: 2012-09-18 Impact factor: 3.240
Authors: Robert A Smith; Dana N Raugi; Charlotte Pan; Papa Salif Sow; Moussa Seydi; James I Mullins; Geoffrey S Gottlieb Journal: Retrovirology Date: 2015-02-05 Impact factor: 4.602
Authors: Joana Cavaco-Silva; Ana Abecasis; Ana Cláudia Miranda; José Poças; Jorge Narciso; Maria João Águas; Fernando Maltez; Isabel Almeida; Isabel Germano; António Diniz; Maria de Fátima Gonçalves; Perpétua Gomes; Celso Cunha; Ricardo Jorge Camacho Journal: PLoS One Date: 2014-03-28 Impact factor: 3.240