Transmitted drug resistance (TDR), the primary acquisition of an HIV variant already resistant to antiretrovirals, affects approximately 15% of all new infections in the United States.
Historically, from the time initial agents in the reverse transcriptase, protease and entry inhibitor classes were introduced, it took 3–5 years before the first case reports of TDR appeared. With the description of the first two cases of transmitted integrase stand-transfer inhibitor resistance, it is only a matter of time before the prevalence of TDR affecting this newest antiretroviral class reaches a level warranting baseline resistance testing for all patients entering care.
References
1.
HallH.I., SongR., RhodesP.Estimation of HIV incidence in the United States. JAMA2008; 300: 520–529.
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.
LittleS.J., FrostS.D., WongJ.K.Persistence of transmitted drug resistance among subjects with primary human immunodeficiency virus infection. J Virol2008; 82: 5510–5518.
4.
HuéS., GiffordR.J., DunnD., FernhillE., PillayD.Demonstration of sustained drug-resistant human immunodeficiency virus type 1 lineages circulating among treatment-naive individuals. J Virol2009; 83: 2645–2654.
5.
SmithD.M., WongJ.K., ShaoH.Long-term persistence of transmitted HIV drug resistance in male genital tract secretions: implications for secondary transmission. J Infect Dis2007; 196: 356–360.
6.
CASCADE Virology Collaboration.The impact of transmitted drug resistance on the natural history of HIV infection and response to first-line therapy. AIDS2006; 20: 21–28.
7.
LennoxJ.L., DejesusE., BergerD.S.Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr2010; 55: 39–48.
8.
Panel on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. 1 December 2009. Department of Health and Human Services. (Accessed 3 January 2011.) Available from http://www.aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL001419.pdf.
9.
RheeS.Y., LiuT.F., KiuchiM.Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Retrovirology2008; 5: 74.
10.
Ceccherini-SilbersteinF., MaletI., FabeniL.Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors. J Antimicrob Chemother2010; 65: 2305–2318.
11.
YoungB., FransenS., GreenbergK.S.Transmission of integrase strand-transfer inhibitor multidrug resistant HIV-1: case report and natural history of response to raltegravir-containing antiretroviral therapy. Antivir Ther2011; doi:10.3851/IMP1748.
12.
BoydS., MaldarelliF., SeretiI.Transmitted raltegravir resistance in an HIV-1 CRF_AG-infected patient. Antivir Ther2011; doi:10.3851/IMP1749.
13.
EriceA., MayersD.L., StrikeD.G.Brief report: primary infection with zidovudine-resistant human immunodeficiency virus type 1. N Engl J Med1993; 328: 1163–1165.
14.
MayersD.L., YerlyS., PerrinL.Prevalence and clinical course of persons seroconverting with AZT-resistant (AZTR) HIV-1 in Switzerland, Australia, and the United States between 1988 and 1994. AIDS Res Hum Retroviruses1995; 11Suppl 1: S162.
RubioA., LealM., PinedaJ.A.Increase in the frequency of mutation at codon 215 associated with zidovudine resistance in HIV-1-infected antiviral-naive patients from 1989 to 1996. AIDS1997; 11: 1184–1186.
17.
CheesemanS.H., HattoxS.E., McLaughlinM.M.Pharmacokinetics of nevirapine: initial single-rising-dose study in humans. Antimicrob Agents Chemother1993; 37: 178–182.
18.
ImrieA., BeveridgeA., GennW., VizzardJ., CooperD.A.Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group. J Infect Dis1997; 175: 1502–1506.
19.
GrantR.M., HechtF.M., WarmerdamM.Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA2002; 288: 181–188.
20.
HechtF.M., GrantR.M., PetropoulosC.J.Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors. N Engl J Med1998; 339: 307–311.
21.
KitchenV.S., SkinnerC., AriyoshiK.Safety and activity of saquinavir in HIV infection. Lancet1995; 345: 952–955.
22.
LittleS.J., HolteS., RoutyJ.P.Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med2002; 347: 385–394.
23.
QuinnT.C., WawerM.J., SewankamboN.Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med2000; 342: 921–929.
24.
DasM., ChuP.L., SantosG.M.Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS ONE2010; 5: e11068.
25.
WoodE., KerrT., MarshallB.D.Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ2009; 38: b1649.
26.
BartmeyerB., KuechererC., HouareauC.Prevalence of transmitted drug resistance and impact of transmitted resistance on treatment success in the German HIV-1 Seroconverter Cohort. PLoS ONE2010; 5: e12718.
27.
VercauterenJ., WensingA.M., van de VijverD.A.Transmission of drug-resistant HIV-1 is stabilizing in Europe. J Infect Dis2009; 200: 1503–1508.
28.
KalichmanS.C., RompaD.HIV treatment adherence and unprotected sex practices in people receiving antiretroviral therapy. Sex Transm Infect2003; 79: 59–61.
29.
FlaksR.C., BurmanW.J., GourleyP.J., RietmeijerC.A., CohnD.L.HIV transmission risk behaviour and its relation to antiretroviral treatment adherence. Sex Transm Dis2003; 30: 399–404.
30.
KozalM.J., AmicoK.R., ChiarellaJ.Antiretroviral resistance and high-risk transmission behaviour among HIV-positive patients in clinical care. AIDS2004; 18: 2185–2189.
31.
NapravnikS., ZakharovaO.M., McKaigR.G.High risk for transmission of HIV and antiretroviral drug-resistant HIV variants among HIV-infected patients in care.3rd International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. 24–27 July 2005, Rio de Janeiro, Brazil. Abstract MoPp0203.
32.
Chin-HongP.V., DeeksS.G., LieglerT.High-risk sexual behaviour in adults with genotypically proven antiretroviral-resistant HIV infection. J Acquir Immune Defic Syndr2005; 40: 463–471.
33.
YarchoanR., KleckerR.W., WeinholdK.J.Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet1986; 327: 575–580.
KilbyJ.M., HopkinsS., VenettaT.M.Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med1998; 4: 1302–1307.
36.
MarkowitzM., Morales-RamirezJ.O., NguyenB.Y.Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr2006; 43: 509–515.
37.
PeuchantO., CapdepontS., RagnaudJ.M.Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort. Antivir Ther2007; 12: 559–562.
