Durability of Antiretroviral Therapy Regimens and Determinants for Change in HIV-1-Infected Patients in the TREAT Asia HIV Observational Database (TAHOD-LITE)
Free accessResearch articleFirst published online February, 2018
Durability of Antiretroviral Therapy Regimens and Determinants for Change in HIV-1-Infected Patients in the TREAT Asia HIV Observational Database (TAHOD-LITE)
The durability of first-line regimen is important to achieve long-term treatment success for the management of HIV infection. Our analysis describes the duration of sequential ART regimens and identifies the determinants leading to treatment change in HIV-positive patients initiating in Asia.
Methods
All HIV-positive adult patients initiating first-line ART in 2003–2013, from eight clinical sites among seven countries in Asia. Patient follow-up was to May 2014. Kaplan–Meier curves were used to estimate the time to second-line ART and third-line ART regimen. Factors associated with treatment durability were assessed using Cox proportional hazards model.
Results
A total of 16,962 patients initiated first-line ART. Of these, 4,336 patients initiated second-line ART over 38,798 person-years (pys), a crude rate of 11.2 (95% CI 10.8, 11.5) per 100 pys. The probability of being on first-line ART increased from 83.7% (95% CI 82.1, 85.1%) in 2003–2005 to 87.9% (95% CI 87.1, 88.6%) in 2010–2013. Third-line ART was initiated by 1,135 patients over 8,078 pys, a crude rate of 14.0 (95% CI 13.3, 14.9) per 100 pys. The probability of continuing second-line ART significantly increased from 64.9% (95% CI 58.5, 70.6%) in 2003–2005 to 86.2% (95% CI 84.7, 87.6%) in 2010–2013.
Conclusions
Rates of discontinuation of first- and second-line regimens have decreased over the last decade in Asia. Subsequent regimens were of shorter duration compared to the first-line regimen initiated in the same year period. Lower CD4+ T-cell count and the use of suboptimal regimens were important factors associated with higher risk of treatment switch.
References
1.
SterneJ.A.C., HernánM.A., LedergerberB.Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study.Lancet2005; 366: 378–384.
2.
MocroftA., LedergerberB., KatlamaC.Decline in the AIDS and death rates in the EuroSIDA study: an observational study.Lancet2003; 362: 22–29.
3.
MadecY., LaureillardD., PinogesL.Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia.AIDS2007; 21: 351–359.
4.
SpacekL.A., ShihabH.M., KamyaM.R.Response to antiretroviral therapy in HIV-infected patients attending a public, urban clinic in Kampala, Uganda.Clin Infect Dis2006; 42: 252–259.
5.
MayM.T., SterneJ.A.C., CostagliolaD.HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis.Lancet2006; 368: 451–458.
6.
BendavidE., HolmesC.B., BhattacharyaJ., MillerG.HIV development assistance and adult mortality in Africa.JAMA2012; 307: 2060–2067.
7.
ToureS., KouadioB., SeylerC.Rapid scaling-up of antiretroviral therapy in 10,000 adults in Côte d'Ivoire: 2-year outcomes and determinants.AIDS2008; 22: 873–882.
8.
PalellaF.J.Jr., ChmielJ.S., MoormanA.C., HolmbergS.D.HIV Outpatient Study Investigators. Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients.AIDS2002; 16: 1617–1626.
9.
Pursuing Later Treatment Option II (PLATO II) project team, Observational HIV Epidemiological Research Europe (COHERE) Group, CostagliolaD.Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study.Lancet Infect Dis2012; 12: 119–127.
10.
ParientiJ-J, MassariV., DescampsD.Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy.Clin Infect Dis2004; 38: 1311–1316.
11.
BangsbergD.R., AcostaE.P., GuptaR.Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness.AIDS2006; 20: 223–231.
12.
ChenR.Y., WestfallA.O., MugaveroM.J.Duration of highly active antiretroviral therapy regimens.Clin Infect Dis2003; 37: 714–722.
13.
AbgrallS., IngleS.M., MayM.T.Durability of first ART regimen and risk factors for modification, interruption or death in HIV-positive patients starting ART in Europe and North America 2002-2009.AIDS2013; 27: 803–813.
14.
ElziL., MarzoliniC., FurrerH.Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008.Arch Intern Med2010; 170: 57–65.
15.
WrightS., BoydM.A., YunihastutiE.Rates and factors associated with major modifications to first-line combination antiretroviral therapy: results from the Asia-Pacific region.PLoS One2013; 8: e64902.
SrikantiahP., GhidinelliM., BachaniD.Scale-up of national antiretroviral therapy programs: progress and challenges in the Asia Pacific region.AIDS2010; 24Suppl 2: S62–S71.
18.
World Health Organization.Scaling up antiretroviral therapy in resource-limited settings: treatment guidelines for a public health approach (2003 revision).Geneva: WHO, 2004. 2003. (Accessed 12 June 2017.) Available from http://www.who.int/hiv/pub/prev_care/en/arvrevision2003en.pdf.
19.
PhuphuakratA., KiertiburanakulS., SungkanuparphS.Current status of HIV treatment in Asia and the Pacific region.Sex Health2014; 11: 119–125.
20.
ZhouJ., LiP., KumarasamyN.Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD).HIV Med2010; 11: 31–39.
21.
De La MataN.L., KumarasamyN., KholV.Improved survival in HIV treatment programmes in Asia.Antivir Ther2016; 21: 517–527.
MakinsonA., MoingV.L., KouanfackC., LaurentC., DelaporteE.Safety of stavudine in the treatment of HIV infection with a special focus on resource-limited settings.Expert Opin Drug Saf2008; 7: 283–293.
BoettigerD.C., KerrS., DitangcoR.Trends in first-line antiretroviral therapy in Asia: results from the TREAT Asia HIV observational database.PLoS One2014; 9: e106525.
27.
SlamaL., LiX., BrownT.Increases in duration of first highly active antiretroviral therapy over time (1996-2009) and associated factors in the Multicenter AIDS Cohort Study.J Acquir Immune Defic Syndr2014; 65: 57–64.
28.
Gonzalez-SernaA., ChanK., YipB.Temporal trends in the discontinuation of first-line antiretroviral therapy.J Antimicrob Chemother2014; 69: 2202–2209.
29.
GallantJ.E., StaszewskiS., PozniakA.L.Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.JAMA2004; 292: 191–201.
30.
SaagM.S., CahnP., RaffiF.Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial.JAMA2004; 292: 180–189.
31.
MadrugaJ.R.V., CassettiI., SuleimanJ.M.A.H.The safety and efficacy of switching stavudine to tenofovir df in combination with lamivudine and efavirenz in hiv-1-infected patients: three-year follow-up after switching therapy.HIV Clin Trials2007; 8: 381–390.
32.
GünthardH.F., AbergJ.A., EronJ.J.Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.JAMA2014; 312: 410–425.
DelfraissyJ-F, FlandreP., DelaugerreC.Lopinavir/ ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients.AIDS2008; 22: 385–393.
35.
VoT.T.N., LedergerberB., KeiserO.Durability and outcome of initial antiretroviral treatments received during 2000–2005 by patients in the Swiss HIV Cohort Study.J Infect Dis2008; 197: 1685–1694.
36.
CicconiP., Cozzi-LepriA., CastagnaA.Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naive patients.HIV Med2010; 11: 104–113.
37.
PalladinoC., BrizV., BellónJ.M.Determinants of highly active antiretroviral therapy duration in HIV-1-infected children and adolescents in Madrid, Spain, from 1996 to 2012.PLoS One2014; 9: e96307.
38.
PalombiL., MarazziM.C., GuidottiG.Incidence and predictors of death, retention, and switch to second-line regimens in antiretroviral- treated patients in sub-Saharan African Sites with comprehensive monitoring availability.Clin Infect Dis2009; 48: 115–122.
39.
ART-LINC of IeDEA Study Group, KeiserO., TweyaH.Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.AIDS2009; 23: 1867–1874.
40.
INSIGHT START Study Group, Lundgren JD, Babiker AG, et al.Initiation of antiretroviral therapy in early asymptomatic HIV infection.N Engl J Med2015; 373: 795–807.
41.
TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, et al.A trial of early antiretrovirals and isoniazid preventive therapy in Africa.N Engl J Med2015; 373: 808–822.
GatellJ., Salmon-CeronD., LazzarinA.Efficacy and safety of atazanavir-based highly active antiretroviral therapy in patients with virologic suppression switched from a stable, boosted or unboosted protease inhibitor treatment regimen: the SWAN Study (AI424-097) 48-week results.Clin Infect Dis2007; 44: 1484–1492.
44.
BoettigerD.C., NguyenV.K., DurierN.Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: results from the TREAT Asia HIV observational database.J Acquir Immune Defic Syndr2015; 68: 186–195.
