Here, we describe an HIV-infected patient with pre-treatment resistance to raltegravir, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the ultimate ability to achieve viral suppression. Pretreatment integrase resistance testing is not routinely performed because transmitted integrase mutations conferring resistance to raltegravir are currently thought to be negligible. We suggest obtaining a pretreatment integrase genotype in patients with transmitted multiclass drug resistance in order to create an optimal first regimen and increase the chance for virological suppression.
References
1.
RossL., LimM.L., LiaoQ.Prevalence of antiretroviral drug resistance and resistance-associated mutations in antiretroviral therapy-naive HIV-infected individuals from 40 United States cities. HIV Clin Trials2007; 8: 1–8.
2.
WheelerW.H., ZiebellR.A., ZabinaH.Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, U.S. – 2006. AIDS2010; 24: 1203–1212.
3.
WeinstockH.S., ZaidiI., HeneineW.The epidemiology of antiretroviral drug resistance among drug-naive HIV-1-infected persons in 10 US cities. J Infect Dis2004; 189: 2174–2180.
4.
Panel on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. (Updated 1 December 2009. Accessed 18 October 2010.) Available from http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL001419.pdf.
5.
BaroncelliS., VillaniP., WeimerL.E.Raltegravir plasma concentrations in treatment-experienced patients receiving salvage regimens based on raltegravir with and without maraviroc coadministration. Ann Pharmacother2010; 44: 838–843.
6.
Prezista (darunavir).Package insert2010. Tibotec, Inc., Yardley, PA, USA.
7.
BennettD.E., CamachoR.J., OteleaD.Drug resistance mutations for surveillance of transmitted HIV-1 drug resistance: 2009 update. PLoS ONE2009; 4: e4724.
8.
FransenS., YoungB., FrantzellA.Control of viral replication following transmission of HIV-1 exhibiting resistance to reverse transcriptase, protease and integrase inhibitors. Antivir Ther2010; 15Suppl 2: A67.
9.
Adjé-TouréC., BileC.E., BorgetM.Y.Polymorphism in protease and reverse transcriptase and phenotypic drug resistance of HIV-1 recombinant CRF02_AG isolates from patients with no prior use of antiretroviral drugs in Abidjan, Côte d'Ivoire. J Acquir Immune Defic Syndr2003; 34: 111–113.
10.
BurdaS.T., ViswanathR., ZhaoJ.HIV-1 reverse transcriptase drug-resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon. J Med Virol2010; 82: 187–196.
11.
JohnsonV.A., Brun-VezinetF., ClotetB.Update of the drug resistance mutations in HIV-1: December 2009. Top HIV Med2009; 17: 138–145.
12.
LiuT.F., ShaferR.W.Web resources for HIV type 1 genotypic-resistance test interpretation. Clin Infect Dis2006; 42: 1608–1618.
13.
Ceccherini-SilbersteinF., BaelenK., ArmeniaD.Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naïve patients have little or no effect on susceptibility to integrase inhibitors. Antimicrob Agents Chemother2010; 54: 3938–3948.
14.
LowA., PradaN., TopperM.Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. Antimicrob Agents Chemother2009; 53: 4275–4282.
15.
RheeS.Y., LiuT.F., KiuchiM.Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Retrovirology2008; 5: 74.
16.
CharpentierC., LaureillardD., PikettyC.High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. AIDS2010; 24: 867–873.
17.
CooperD.A., SteigbigelR.T., GatellJ.M.Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med2008; 359: 355–365.
18.
CarrJ.K., OsinusiA., FlynnC.P., GilliamB.L., MaheshwariV., ZhaoR.Y.Two independent epidemics of HIV in Maryland. J Acquir Immune Defic Syndr2010; 54: 297–303.
19.
GaoX., O'BrienT.R., WelzelT.M.HLA-B alleles associate consistently with HIV heterosexual transmission, viral load, and progression to AIDS, but not susceptibility to infection. AIDS2010; 24: 1835–1840.
20.
HatanoH., LampirisH., FransenS.Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy. J Acquir Immune Defic Syndr2010; 54: 389–393.
21.
GoethalsO., VosA., Van GinderenM.Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Virology2010; 402: 338–346.
22.
KobayashiM., NakaharaK., SekiT.Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res2008; 80: 213–222.
