Transmission of drug-resistant HIV is a potential threat to the substantial clinical benefit of highly active antiretroviral therapy (HAART). To explore the background for the low rates of drug resistance transmission (2–5%) in our population, we estimated acquisition of HIV drug resistance and examined temporal trends in the prevalence of patients at risk of transmitting drug-resistant HIV.
Methods
The study population included all 4,025 patients from The Danish HIV Cohort Study seen during the period 1995–2004. Virological failure to a given drug class was defined as a viral load (VL) >1,000 copies/ml for 120 days while on a HAART regimen including that drug class. In addition, receiving nucleoside reverse transcriptase inhibitors (NRTIs) for 180 days before HAART counted as NRTI failure irrespective of VL. Having experienced failure was considered a proxy for harbouring drug-resistant virus in subsequent observation time. Patients with a current VL >1,000 copies/ml were considered at risk of transmitting HIV.
Results
We found a decrease from 1997 to 2004 in the prevalence of potential transmitters of drug-resistant HIV. The number of these patients with previous NRTI failure decreased from 429 (24% of all patients) in 1998 to 213 (8.0% of all patients) in 2004. Previous protease inhibitor (PI) failure peaked at 279 (14%) in 1999, declining to 142 (5.3%) in 2004. Previous NNRTI failure peaked at 121 patients (4.7%) in 2002, and occurred in 113 patients (4.2%) in 2004. Of all 686 potential transmitters in 2004, 31% had previously experienced NRTI failure, 21% PI failure, and 16% non-NRTI failure.
Conclusion
In the population of HIV-infected individuals in Denmark with complete follow-up, the number at risk of transmitting drug-resistant virus declined over time.
References
1.
RichmanD.D., MortonS.C., WrinT.The prevalence of antiretroviral drug resistance in the United States.AIDS2004; 18: 1393–1401.
2.
PhillipsA.N., DunnD., SabinC.Long term probability of detection of HIV-1 drug resistance after starting anti-retroviral therapy in routine clinical practice.AIDS2005; 19: 487–494.
3.
BlowerS.M., AschenbachA.N., GershengornH.B., KahnJ.O.Predicting the unpredictable: transmission of drug-resistant HIV.Nat Med2001; 7: 1016–1020.
4.
PillayD., GreenH., MatthiasR.; UK Collaborative Group on HIV Drug Resistance. Estimating HIV-1 drug resistance in antiretroviral-treated individuals in the United Kingdom.J Infect Dis2005; 192: 967–973.
DunnD.T., GreenH., MatthiasR.Prevalence of reduced drug susceptibility in treatment-naive patients in the UK.13th International HIV Drug Resistance Workshop. 8–12 June 2004, Tenerife, Spain. Abstract 96.
7.
LittleS.J., HolteS., RoutyJ.P.Antiretroviral-drug resistance among patients recently infected with HIV.N Engl J Med2002; 347: 385–394.
8.
PillayD.Current patterns in the epidemiology of primary HIV drug resistance in North America and Europe.Antivir Ther2004; 9: 695–702.
9.
RoutyJ.P., MachoufN., EdwardesM.D.Factors associated with a decrease in the prevalence of drug resistance in newly HIV-1 infected individuals in Montreal.AIDS2004; 18: 2305–2312.
10.
AmmaranondP., CunninghamP., OelrichsR.Rates of transmission of antiretroviral drug resistant strains of HIV-1.J Clin Virol2003; 26: 153–161.
11.
BezemerD., JurriaansS., PrinsM.Declining trend in transmission of drug-resistant HIV-1 in Amsterdam.AIDS2004; 18: 1571–1577.
12.
WensingA.M., van de VijverD.A., AngaranoG.Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management.J Infect Dis2005; 192: 958–966.
13.
JorgensenL.B., ChristensenM.B., GerstoftJ.Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark.Scand J Infect Dis2003; 35: 800–807.
14.
Jensen-FangelS., PedersenC., LarsenC.S., TaurisP., MøllerA., ObelN.Changing demographics in an HIV-infected population: results from an observational cohort study in Western Denmark.Scand J Infect Dis2001; 33: 765–770.
15.
LohseN., HansenA.B., Jensen-FangelS.Demographics of HIV-1 infection in Denmark: Results from The Danish HIV Cohort Study.Scand J Infect Dis2005; 37: 338–343.
16.
LohseN., ObelN., KronborgG.Declining risk of triple-class antiretroviral drug failure in Danish HIV-infected individuals.AIDS2005; 19: 815–822.
17.
LedergerberB., LundgrenJ.D., WalkerA.S.Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes.Lancet2004; 364: 51–62.
18.
NapravnikS., EdwardsD., StewartP., StalzerB., MattesonE., EronJ.J.Jr., HIV-1 drug resistance evolution among patients on potent combination antiretroviral therapy with detectable viremia.J Acquir Immune Defic Syndr2005; 40: 34–40.
19.
MocroftA., LedergerberB., ViardJ.P.Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group.J Infect Dis2004; 190: 1947–1956.
20.
LohseN., KronborgG., GerstoftJ.Virological control during the first 6–18 months after initiating HAART as a predictor for mortality, CD4+ cell increase, and viral suppression.Clin Infect Dis2006; 42: 136–144.
21.
RogeB., BarfodT., KirkO.Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study.HIV Med2004; 5: 344–351.
22.
WalmsleyS., BernsteinB., KingM.Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection.N Engl J Med2002; 346: 2039–2046.
23.
DybulM., FauciA.S., BartlettJ.G., KaplanJ.E., PauA.K.Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.Ann Intern Med2002; 137: 381–433.
Leigh BrownA.J., FrostS.D., MathewsW.C.Transmission fitness of drug-resistant human immunodeficiency virus and the prevalence of resistance in the antiretroviral-treated population.J Infect Dis2003; 187: 683–686.
26.
AuvertB., TaljaardD., LagardeE., Sobngwi-TambekouJ., SittaR., PurenA.Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial.PLoS Med2005; 2: e298.
27.
SextonJ., GarnettG., RottingenJ.A.Metaanalysis and metaregression in interpreting study variability in the impact of sexually transmitted diseases on susceptibility to HIV infection.Sex Transm Dis2005; 32: 351–357.
28.
ShafferN., RoongpisuthipongA., SiriwasinW.Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.J Infect Dis1999; 179: 590–599.
29.
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.
30.
GrayR.H., WawerM.J., BrookmeyerR.Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.Lancet2001; 357: 1149–1153.
31.
CastillaJ., Del RomeroJ., HernandoV., MarincovichB., GarciaS., RodriguezC.Effectiveness of highly active anti-retroviral therapy in reducing heterosexual transmission of HIV.J Acquir Immune Defic Syndr2005; 40: 96–101.
