A major barrier to successful viral suppression in HIV type 1 (HIV-1)-infected individuals is the emergence of virus resistant to antiretroviral drugs. We explored the evolution of genotypic drug resistance prevalence in treatment-failing patients from 1999 to 2005 in a clinical cohort.
Patients and Methods
Prevalence of major International AIDS Society-USA HIV-1 drug resistance mutations was measured over calendar years in a population with treatment failure and undergoing resistance testing. Predictors of the presence of resistance mutations were analysed by logistic regression.
Results
Significant reductions of the prevalence of resistance to all three drug classes examined were observed. This was accompanied by a reduction in the proportion of treatment-failing patients. Independent predictors of drug resistance were the earlier calendar year, prior use of suboptimal nucleoside analogue therapy, male sex and higher CD4 levels at testing.
Conclusions
In a single clinical cohort, we observed a decrease in the prevalence of resistance to all three examined antiretroviral drug classes over time. If this finding is confirmed in multicentre cohorts it may translate into reduced transmission of drug-resistant virus from treated patients.
References
1.
DeGruttolaV., DixL., D'AquilaR.The relation between baseline HIV drug resistance and response to anti-retroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan.Antivir Ther2000; 5: 41–48.
2.
HirschM.S., Brun-VezinetF., ClotetB.Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA Panel.Clin Infect Dis2003; 37: 113–128.
3.
GottliebG.S., HawesS.E., AgneH.D.Lower levels of HIV RNA in semen in HIV-2 compared with HIV-1 infection: implications for differences in transmission.AIDS2006; 20: 895–900.
4.
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 Dis2006; 192: 958–966.
5.
JohnsonV.A., Brun-VézinetF., ClosetB.Update of the Drug Resistance Mutations in HIV-1: Fall 2005.Top HIV Med2005; 13: 125–131.
6.
TamaletC., FantiniJ., TouresC., YahiN.Resistance of HIV-1 to multiple antiretroviral drugs in France: a 6-year survey (1997–2002) based on an analysis of over 7000 genotypes.AIDS2003; 17: 2383–2388.
7.
ScottP., ArnoldE., EvansB.Surveillance of HIV antiretroviral drug resistance in treated individuals in England: 1998–2000.J Antimicrob Chemother2004; 53: 469–473.
8.
RichmanD.D., MortonS.C., WrinT.F.The prevalence of antiretroviral drug resistance in the United States.AIDS2004; 18: 1393–1401.
9.
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.
10.
Health Protection Agency.CDR Weekly2006; 16: 14–18.
11.
KempfD.J., KingM.S., BernsteinB.Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine.J Infect Dis2004; 189: 51–60.
12.
MacManusS., YatesP.J., ElstonR.C., WhiteS., RichardsN., SnowdenW.GW433908/ritonavir once daily in antiretroviral therapy-naive HIV-infected patients: absence of protease resistance at 48 weeks.AIDS2004; 18: 651–655.
13.
LohseN., ObelN., KronborgG.Declining prevalence of HIV-infected individuals at risk of transmitting drug-resistant HIV in Denmark during 1997–2004.Antivir Ther2006; 11: 591–600.
14.
TemesgenZ., CainelliF., PoeschlaE.M.Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults.Lancet Infect Dis2006; 6: 496–507.
15.
LedergerberB., WalkerA.S., SabinC.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.
16.
MurriR., LepriA.C., CicconiP.Is moderate HIV viremia associated with a higher risk of clinical progression in HIV-infected people treated with highly active antiretroviral therapy: evidence from the Italian cohort of antiretroviral-naive patients study.J Acquir Immune Defic Syndr2006; 41: 23–30.
