Skip to content
2000
Volume 23, Issue 2
  • ISSN: 1570-162X
  • E-ISSN: 1873-4251

Abstract

Introduction

In the changing HIV treatment landscape, the focus shifts to persons living with HIV (PLH) experiencing virological non-suppression on second-line antiretroviral therapy (ART). This includes understanding viral genetic profiles, antiretroviral susceptibility, and the effectiveness of protease inhibitors (PIs) amid evolving dolutegravir-based regimen recommendations.

Methods

In this retrospective study, PLH with first-line ART failure transitioned to second-line ART (dual NRTI + ritonavir-boosted PI) between September 2015 and October 2018. Eligible patients were ≥ 13 years old, with ≥ 9 months on first-line ART, and confirmed adherence at first- line regimen failure. Conducted at a Northern Indian tertiary hospital, this 5 year follow-up examined virological outcomes and drug resistance. Follow-up included initial viral-load (VL) and CD4 testing at 6-months, subsequent VL testing every 6-12 months, clinical evaluations, and infection screenings. Data on demographics, treatment history, virological-failure (VF), and drug-resistance testing (DRT) (Viroseq HIV-1 genotyping-system) were analysed using Kaplan-Meier and Competing-risk analysis, with appropriate censoring and imputation for events like death, transfer-out, treatment discontinuation/ interruption, loss to follow-up (LTFU), or ART-regimen change.

Results

219 PLH shifted to ritonavir-boosted PI based second-line ART after 68 (median) months (IQR: 68) of first-line ART exposure and were followed up for 57 (median) months (IQR: 48), totalling 11,548 person-months (PM) of follow-up. Virological outcomes were assessed in 201 PLH. VF cumulative-incidence (Kaplan-Meier-analysis) ranged from 6.9% at 36 months to 15.9% at 60 months. Imputation scenarios showed a potential range, with worst-case incidences of 16.2% at 36 months and 29.4% at 60 months. Cumulative-incidence function (CIF) of VF (Competing-risk-analysis) ranged from 6.5% at 36 months to 12.7% at 60 months. Among 171 PLH with complete VL data, VF incidence was 2.7 per 1000 PM (n=29), with 94.7% achieving nadir VL <1000 cp/mL. VF with PI-mutation (VF-M) analysis, including LTFU patients (n=183), showed CIF for VFM of 2.3% at 36 months and 4.9% at 60 months. DRT (n=23-sequences) revealed 17.4% lopinavir resistance, 34.8% atazanvir resistance, and darunavir (DRV) cross-resistance in three sequences. Overall, 26.1% had no significant drug-resistance mutations, 39.1% had NNRTI resistance, but no PI DRMs, and only 34.8% (of 23-PLH who underwent DRT) potentially required third-line ART.

Conclusion

This 5-year longitudinal study highlights the resilience of PIs in second-line ART. The incidence of VF with PI-resistance was notably low, indicating the ongoing effectiveness of PIs in managing PLH on second-line ART and the possibility of recycling PIs in subsequent ART regimens for these patients. Cross-resistance to DRV patients highlights the need for enhanced treatment monitoring.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/chr/10.2174/011570162X344689250331081024
2025-04-14
2025-10-26

  • From This Site

    /content/journals/chr/10.2174/011570162X344689250331081024
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. World Health Organization. World Health Statistics 2023: Monitoring Health for the SDGs, Sustainable Development Goals. Geneva: World Health Organization; 2023. Available from: https://www.who.int/publications/i/item/9789240074323
  2. Global HIV Programme.2020Available from: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics
  3. Understanding Fast-Track 2015. Available from: https://www.unaids.org/en/resources/documents/2015/201506_JC2743_Understanding_FastTrack
  4. GregsonJ TangM NdembiN HamersRL MarconiVC BrooksK Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: A multicentre retrospective cohort study.Lancet Infect Dis.2016165565575
     [Google Scholar]
  5. GuptaR.K. GregsonJ. ParkinN. Haile-SelassieH. TanuriA. Andrade ForeroL. KaleebuP. WateraC. AghokengA. MutendaN. DzangareJ. HoneS. HangZ.Z. GarciaJ. GarciaZ. MarchorroP. BetetaE. GironA. HamersR. InzauleS. FrenkelL.M. ChungM.H. de OliveiraT. PillayD. NaidooK. KharsanyA. KugathasanR. CutinoT. HuntG. Avila RiosS. DohertyM. JordanM.R. BertagnolioS. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: A systematic review and meta-regression analysis.Lancet Infect. Dis.201818334635510.1016/S1473‑3099(17)30702‑829198909
     [Google Scholar]
  6. KantersS. VitoriaM. ZorattiM. DohertyM. PenazzatoM. RangarajA. FordN. ThorlundK. AnisP.A.H. KarimM.E. MofensonL. ZashR. CalmyA. KredoT. BansbackN. Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400 mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis.EClinicalMedicine20202810057310.1016/j.eclinm.2020.10057333294805
     [Google Scholar]
  7. Sankalak: Status of National AIDS Response2021Available from: https://www.aidsdatahub.org/resource/sankalak-status-national-aids-response
  8. World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach, 2nd ed. Geneva: World Health Organization; 2016. Available from: https://www.who.int/publications/i/item/9789241549684
  9. LevisonJ.H. OrrellC. GallienS. KuritzkesD.R. FuN. LosinaE. FreedbergK.A. WoodR. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.PLoS One201273e3214410.1371/journal.pone.003214422427821
     [Google Scholar]
  10. HosseinipourM.C. GuptaR.K. Van ZylG. EronJ.J. NachegaJ.B. Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings.J Infect Dis2013207Suppl 2S49S56
     [Google Scholar]
  11. GrinsztejnB. HughesM.D. RitzJ. SalataR. MugyenyiP. HoggE. WieclawL. GrossR. GodfreyC. CardosoS.W. BukuruA. MakangaM. FaesenS. MaveV. Wangari NdegeB. Nerette FontainS. SamanekaW. SecoursR. van SchalkwykM. MngqibisaR. MohapiL. ValenciaJ. SugandhavesaP. MontalbanE. AvihingsanonA. SantosB.R. KumarasamyN. KanyamaC. SchooleyR.T. MellorsJ.W. WallisC.L. CollierA.C. GrinsztejnB. MugyenyiP.N. CollierA. SalataR. GodfreyC. HoggE. HughesM. RitzJ. WieclawL. SiseT. MellorsJ.W. WallisC. FletcherC.V. GandhiM. GrossR. SchooleyR.T. WalenskyR. van SchalkwykM. FaesenS. MngqibisaR. ValenciaJ. MontalbanE. KumarasamyN. KanyamaC. CardosoS.W. SantosB.R. MansfieldB. MugerwaH. NdegeB.W. SecoursR. SamanekaW. KadamD. MaveV. MakangaM. FontainS.N. SugandhavesaP. AvihingsanonA. NakibuukaL. NassoloH. AnthonyP. KulkarniV. NsubugaM. van WykJ. RooneyJ. van DelftY. LeavittR. LukR. BennsA. HovindL. ShahkolahiA. A5288 Team Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): A prospective strategy study.Lancet HIV201969e588e60010.1016/S2352‑3018(19)30146‑831371262
     [Google Scholar]
  12. MusanaH. SsensambaJ.T. NakafeeroM. MugerwaH. KiweewaF.M. SerwaddaD. SsaliF. Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda.AIDS Res. Ther.20211811710.1186/s12981‑021‑00338‑y33882938
     [Google Scholar]
  13. HaftuA.Z. DestaA.A. BezabihN.M. KahsayA.B. KidaneK.M. ZewdieY. Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study.Plos One2020159e0239191
     [Google Scholar]
  14. Pujades-RodríguezM. BalkanS. ArnouldL. BrinkhofM.A.W. CalmyA. Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.JAMA2010304330331210.1001/jama.2010.98020639564
     [Google Scholar]
  15. TsegayeA.T. WubshetM. AwokeT. Addis AleneK. Predictors of treatment failure on second-line antiretroviral therapy among adults in northwest Ethiopia: A multicentre retrospective follow-up study.BMJ Open2016612e01253710.1136/bmjopen‑2016‑01253727932339
     [Google Scholar]
  16. EdessaD. SisayM. AsefaF. Second-line HIV treatment failure in sub-Saharan Africa: A systematic review and meta-analysis.PLoS One2019147e022015910.1371/journal.pone.022015931356613
     [Google Scholar]
  17. SalviS RaichurP KadamD SangleS GupteN NevrekarN Virological failure among people living with HIV receiving second-line antiretroviral therapy in Pune, India.BMC Infect Dis.2022221951
     [Google Scholar]
  18. SaravananS. VidyaM. BalakrishnanP. KantorR. SolomonS.S. KatzensteinD. KumarasamyN. YeptomiT. SivamalarS. RifkinS. MayerK.H. SolomonS. Viremia and HIV-1 drug resistance mutations among patients receiving second-line highly active antiretroviral therapy in Chennai, Southern India.Clin. Infect. Dis.2012547995100010.1093/cid/cir96722323567
     [Google Scholar]
  19. KhanS DasM AndriesA DeshpandeA MansoorH SaranchukP Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India.Glob Health Action2014724861
     [Google Scholar]
  20. ChakravartyJ. SundarS. ChourasiaA. SinghP.N. KurleS. TripathyS.P. ChaturbhujD.N. RaiM. AgarwalA.K. MishraR.N. ParanjapeR.S. Outcome of patients on second line antiretroviral therapy under programmatic condition in India.BMC Infect. Dis.201515151710.1186/s12879‑015‑1270‑826572102
     [Google Scholar]
  21. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV.2023Available from: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/virologic-failure
  22. LeeY.L. LinK.Y. ChengS.H. LuP.L. WangN.C. HoM.W. YangC.J. LiouB.H. TangH.J. HuangS.S. HuangS.H. ChenT.C. LinC.Y. LinS.P. LeeY.T. HungC.C. Dual therapy with dolutegravir plus boosted protease inhibitor as maintenance or salvage therapy in highly experienced people living with HIV.Int. J. Antimicrob. Agents202158310640310.1016/j.ijantimicag.2021.10640334289404
     [Google Scholar]
  23. OrganizationN.A.C. National technical guidelines on anti retroviral treatment.2018Available from: https://naco.gov.in/sites/default/files/NACO-NationalTechnicalGuidelinesonART_October2018%281%29.pdf
  24. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: Recommendations for a public health approach.2021Available from: https://apps.who.int/iris/rest/bitstreams/1357089/retrieve
  25. HIV Drug Resistance Database Version 9.12022Available from: https://hivdb.stanford.edu/
  26. PatelA.K. PatelK.K. PujariS. PatelJ.K. KumarA. Virological outcome and frequency of low-level viremia in patients receiving generic dolutegravir-containing regimen at a large tertiary care clinic in Western India.Indian J. Sex. Transm. Dis. AIDS2021421313710.4103/ijstd.IJSTD_34_2034765935
     [Google Scholar]
  27. Rapid advice : Antiretroviral therapy for HIV infection in adults and adolescents2009Available from: https://iris.who.int/handle/10665/107280
  28. LumuI. MusaaziJ. CastelnuovoB. Durability of second-line anti-retroviral therapy in a resource-limited setting: An 11-year analytical cohort.SSRN Electron J202210.2139/ssrn.4057138
     [Google Scholar]
  29. BoettigerDC NguyenVK DurierN BuiH V. Heng SimBL AzwaI 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 Syndr2015682186195
     [Google Scholar]
  30. PatonN.I. KityoC. HoppeA. ReidA. KambuguA. LugemwaA. van OosterhoutJ.J. KiconcoM. SiikaA. MwebazeR. AbwolaM. AbongomeraG. MweembaA. AlimaH. AtwongyeireD. NyirendaR. BolesJ. ThompsonJ. TumukundeD. ChidzivaE. MambuleI. ArribasJ.R. EasterbrookP.J. HakimJ. WalkerA.S. MugyenyiP. EARNEST Trial Team Assessment of second-line antiretroviral regimens for HIV therapy in Africa.N. Engl. J. Med.2014371323424710.1056/NEJMoa131127425014688
     [Google Scholar]
  31. AjoseO. MookerjeeS. MillsE.J. BoulleA. FordN. Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings.AIDS201226892993810.1097/QAD.0b013e328351f5b222313953
     [Google Scholar]
  32. StockdaleA.J. SaundersM.J. BoydM.A. BonnettL.J. JohnstonV. WandelerG. SchoffelenA.F. CiaffiL. StaffordK. CollierA.C. PatonN.I. GerettiA.M. Effectiveness of protease inhibitor/nucleos(t)ide reverse transcriptase inhibitor–based second-line antiretroviral therapy for the treatment of human immunodeficiency virus type 1 infection in Sub-Saharan Africa: A systematic review and meta-analysis.Clin. Infect. Dis.201866121846185710.1093/cid/cix110829272346
     [Google Scholar]
  33. SarfoF.S. CastelnuovoB. FantiI. FeldtT. IncardonaF. KaiserR. LwangaI. MarroneG. SonnerborgA. TufaT.B. ZazziM. De LucaA. Longer-term effectiveness of protease-inhibitor-based second line antiretroviral therapy in four large sub-Saharan African clinics.J. Infect.201978540240810.1016/j.jinf.2019.03.00330849438
     [Google Scholar]
  34. PatelD DesaiM ShahA DikshitR Early outcome of second line antiretroviral therapy in treatment-experienced human immunodeficiency virus positive patients.Perspect Clin Res201344215220
     [Google Scholar]
  35. National guidelines for HIV care and treatment 2021.2021Available from:http://naco.gov.in/sites/default/files/National_Guidelines_for_HIV_Care_and_Treatment_2021.pdf
    [Google Scholar]
  36. ChimukangaraB. LessellsR.J. SartoriusB. GounderL. ManyanaS. PillayM. SinghL. GiandhariJ. GovenderK. SamuelR. MsomiN. NaidooK. de OliveiraT. MoodleyP. ParboosingR. HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral therapy in KwaZulu-Natal Province, South Africa.J. Glob. Antimicrob. Resist.20222946847510.1016/j.jgar.2021.10.02334785393
     [Google Scholar]
  37. CohenK StewartA KengneAP LeisegangR CoetseeM MaharajS A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy.J Acquir Immune Defic Syndr2019803325329
     [Google Scholar]
  38. Nzengui-NzenguiG.F. MourembouG. M’boyis-KamdemH. Kombila-KoumavorA.C. Ndjoyi-MbiguinoA. HIV protease resistance mutations in patients receiving second-line antiretroviral therapy in Libreville, Gabon.BMC Infect. Dis.202424131610.1186/s12879‑024‑09156‑938486188
     [Google Scholar]
  39. BircherR.E. NtamatungiroA.J. GlassT.R. MnzavaD. NyuriA. MapesiH. ParisD.H. BattegayM. KlimkaitT. WeisserM. KIULARCO study group High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania – A prospective cohort study.PLoS One2020151e022760010.1371/journal.pone.022760031929566
     [Google Scholar]
  40. HarriganR. DongW. AlexanderC. Abstracts of the 2nd IAS (International AIDS Society) on HIV pathogenesis and treatment. Paris, France, 13-16 July 2003.Antivir Ther20038Suppl 1S187S557
     [Google Scholar]
  41. BangsbergD.R. MossA.R. DeeksS.G. Paradoxes of adherence and drug resistance to HIV antiretroviral therapy.J. Antimicrob. Chemother.200453569669910.1093/jac/dkh16215044425
     [Google Scholar]
  42. BoenderT.S. HamersR. OndoaP. Protease inhibitor resistance at 2nd-line HIV treatment failure in sub-Saharan Africa.Top. Antivir. Med.201624E-1195196
     [Google Scholar]
  43. KantorR DeLongA SchreierL HIV-1 second-line failure and drug resistance at high-level and low-level viremia in Western Kenya.AIDS2018321724852496
     [Google Scholar]
  44. Jannat-KhahDP UnterbrinkM McNairyM Treating loss- to-follow-up as a missing data problem: A case study using a longitudinal cohort of HIV-infected patients in Haiti.BMC Public Health20181811269
     [Google Scholar]
/content/journals/chr/10.2174/011570162X344689250331081024
Loading
Virological Failure And HIV-1 Drug Resistance in Indian Adults and Adolescents on Protease Inhibitor Based Second-line Antiretroviral Therapy: A Five-year Follow-up Study
Cur. HIV Res. 23, 133 (2025); https://doi.org/10.2174/011570162X344689250331081024
/content/journals/chr/10.2174/011570162X344689250331081024
/content/journals/chr/10.2174/011570162X344689250331081024
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Antiretroviral therapy; atazanavir; dolutegravir; drug resistance; highly active; HIV infections; HIV protease inhibitors; lopinavir; reverse transcriptase inhibitors

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test