Virological suppression and clinical management in response to viremia in South African HIV treatment program: A multicenter cohort study
Autoři:
Lucas E. Hermans aff001; Sergio Carmona aff004; Monique Nijhuis aff001; Hugo A. Tempelman aff003; Douglas D. Richman aff007; Michelle Moorhouse aff002; Diederick E. Grobbee aff003; Willem D. F. Venter aff002; Annemarie M. J. Wensing aff001
Působiště autorů:
Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands
aff001; Wits Reproductive Health and HIV Institute (Wits RHI), University of the Witwatersrand, Johannesburg, South Africa
aff002; Ndlovu Research Consortium, Elandsdoorn, South Africa
aff003; Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa
aff004; National Health Laboratory Service (NHLS), Johannesburg, South Africa
aff005; University of the Witwatersrand, Johannesburg, South Africa
aff006; Center for AIDS Research, University of California San Diego, United States of America
aff007; VA San Diego Healthcare System, California, United States of America
aff008; Clinical Epidemiology, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands
aff009; Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands
aff010
Vyšlo v časopise:
Virological suppression and clinical management in response to viremia in South African HIV treatment program: A multicenter cohort study. PLoS Med 17(2): e1003037. doi:10.1371/journal.pmed.1003037
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pmed.1003037
Souhrn
Background
Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions.
Methods and findings
Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9–43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61–265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16–54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35–127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding.
Conclusions
In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.
Klíčová slova:
African people – Antiretroviral therapy – Antiretrovirals – Data management – HIV epidemiology – T cells – Viral load – Viremia
Zdroje
1. UNAIDS. 90-90-90 An ambitious treatment target to help end the AIDS epidemic. 2014 [cited 2020 Feb 6]. Available from: https://www.unaids.org/en/resources/documents/2017/90-90-90
2. Joint United Nations Programme on HIV/AIDS (UNAIDS). Ending AIDS: Progress towards the 90-90-90 targets. 2017 [cited 2020 Feb 6]. Available from: http://www.unaids.org/en/resources/documents/2017/20170720_Global_AIDS_update_2017
3. Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390:2073–82. doi: 10.1016/S0140-6736(17)32340-1 28867499
4. Kohler P, Schmidt AJ, Cavassini M, Furrer H, Calmy A, Battegay M, et al. The HIV care cascade in Switzerland: Reaching the UNAIDS/WHO targets for patients diagnosed with HIV. AIDS. 2015;29(18):2509–15. doi: 10.1097/QAD.0000000000000878 26372488
5. Gisslén M, Svedhem V, Lindborg L, Flamholc L, Norrgren H, Wendahl S, et al. Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets. HIV Med. 2017;18(4):305–7. doi: 10.1111/hiv.12431 27535540
6. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2016 [cited 2020 Feb 6]. Available from: https://www.who.int/hiv/pub/arv/arv-2016/en/ 27466667
7. Ryscavage P, Kelly S, Li JZ, Richard Harrigan P, Taiwo B. Significance and clinical management of persistent low-level viremia and very-low-level viremia in HIV-1-infected patients. Antimicrob Agents Chemother. 2014;58(7):3585–98. doi: 10.1128/AAC.00076-14 24733471
8. Hermans LE, Moorhouse M, Carmona S, Grobbee DE, Hofstra LM, Richman DD, et al. Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes: A multicentre cohort study. Lancet Infect Dis. 2017;18(2):188–97. doi: 10.1016/S1473-3099(17)30681-3 29158101
9. European AIDS Clinical Society. EACS Guidelines Version 9.0. 2018 [cited 2020 Feb 6]. Available from: www.eacsociety.org/files/2018_guidelines-9.1-english.pdf
10. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. 2018 [cited 2020 Feb 6]. Available from: https://aidsinfo.nih.gov/guidelines
11. Barth RE, Aitken SC, Tempelman H, Geelen SP, van Bussel EM, Hoepelman AIM, et al. Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. Antivir Ther. 2012;17(2):377–86. doi: 10.3851/IMP2010 22297391
12. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe J, Taylor H, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997;387(6629):183–8. doi: 10.1038/387183a0 9144289
13. Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Peteresen I, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Med. 2015;12(10):1–22.
14. Johnson LF, May MT, Dorrington RE, Cornell M, Boulle A, Egger M, et al. Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study. PLoS Med. 2017;14(12):1–17.
15. Granich R, Gupta S, Hersh B, Williams B, Montaner J, Young B, et al. Trends in AIDS deaths, new infections and ART coverage in the top 30 countries with the highest AIDS mortality burden; 1990–2013. PLoS ONE. 2015;10(7):1–16.
16. Swenson LC, Min JE, Woods CK, Cai E, Li JZ, Montaner JSG, et al. HIV drug resistance detected during low-level viraemia is associated with subsequent virologic failure. AIDS. 2014;28(8):1125–34. doi: 10.1097/QAD.0000000000000203 24451160
17. Labhardt ND, Bader J, Lejone TI, Ringera I, Hobbins MA, Fritz C, et al. Should viral load thresholds be lowered? Medicine (Baltimore). 2016;95(28):e3985.
18. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment—Guidance for Industry. 2015 [cited 2020 Feb 6]. Available from: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm355128.pdf
19. Fox MP, Rosen S. Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta- analysis 2008–2013. J Acquir Immune Defic Syndr. 2016;69(1):98–108.
20. Chammartin F, Zürcher K, Keiser O, Weigel R, Chu K, Kiragga AN, et al. Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis. Clin Infect Dis. 2018;67(11):1643–52. doi: 10.1093/cid/ciy347 29889240
21. Bulage L, Ssewanyana I, Nankabirwa V, Nsubuga F, Kihembo C, Pande G, et al. Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014-July 2015. BMC Infect Dis. 2017;17(326):1–11.
22. Fielding KL, Charalambous S, Stenson AL, Pemba LF, Martin DJ, Wood R, et al. Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: a cohort study. BMC Infect Dis. 2008;8(93):1–8.
23. The Antiretroviral Therapy in Low Income Countries (ART-LINC) Collaboration of the International Epidemiologic Databases to Evaluate AIDS. Mortality Associated With Discordant Responses to Antiretroviral Therapy in Resource-Constrained Settings. J Acquir Immune Defic Syndr. 2010;53(1):70–7. doi: 10.1097/QAI.0b013e3181c22d19 20035163
24. Keiser O, Tweya H, Braitstein P, Dabis F, Phail P, Nash D, et al. Mortality after failure of antiretroviral therapy in sub-Saharan Africa. Trop Med Int Heal. 2010;15(2):251–8.
25. Hoffmann CJ, Charalambous S, Sim J, Ledwaba J, Schwikkard G, Chaisson RE, et al. Viremia, resuppression, and the time to resistance in HIV subtype C during first line antiretroviral therapy in South Africa. Clin Infect Dis. 2009;49(12):1928–35. doi: 10.1086/648444 19911963
26. McCluskey SM, Boum Y, Musinguzi N, Haberer JE, Martin JN, Hunt PW, et al. Brief Report: Appraising Viral Load Thresholds and Adherence Support Recommendations in the World Health Organization Guidelines for Detection and Management of Virologic Failure. J Acquir Immune Defic Syndr. 2017;76(2):183–7. doi: 10.1097/QAI.0000000000001479 28628529
27. Levison JH, Orrell C, Losina E, Lu Z, Freedberg KA, Wood R. Early outcomes and the virologic impact of delayed treatment switching on second-line therapy in an antiretroviral roll-out program in South Africa. Antivir Ther. 2011;16(6):853–61. doi: 10.3851/IMP1819 21900717
28. Glass TR, Motaboli L, Nsakala B, Lerotholi M, Vanobberghen F, Id AA, et al. The viral load monitoring cascade in a resource-limited setting: A prospective multicentre cohort study after introduction of routine viral load monitoring in rural Lesotho. PLoS ONE. 2019;14(8):e0220337. doi: 10.1371/journal.pone.0220337 31461455
29. Boulle A, Van Cutsem G, Hilderbrand K, Cragg C, Abrahams M, Mathee S, et al. Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS. 2010;24(4):563–72. doi: 10.1097/QAD.0b013e328333bfb7 20057311
30. Bekker L-G, Alleyne G, Baral S, Cepeda J, Daskalakis D, Dowdy D, et al. Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission. Lancet. 2018;392(10144):312–58. doi: 10.1016/S0140-6736(18)31070-5 30032975
31. Aghokeng AF, Monleau M, Eymard-Duvernay S, Dagnra A, Kania D, Ngo-Giang-Huong N, et al. Extraordinary heterogeneity of virological outcomes in patients receiving highly antiretroviral therapy and monitored with the World Health Organization public health approach in sub-saharan Africa and southeast Asia. Clin Infect Dis. 2014;58(1):99–109. doi: 10.1093/cid/cit627 24076968
32. Fulcher JA, Du Y, Zhang T-H, Sun R, Landovitz RJ. Emergence of Integrase Resistance Mutations During Initial Therapy Containing Dolutegravir. Clin Infect Dis. 2018;67(5):791–794. doi: 10.1093/cid/ciy228 29933437
33. Wijting IEA, Lungu C, Rijnders BJA, van der Ende ME, Pham HT, Mesplede T, et al. HIV-1 resistance dynamics in patients failing dolutegravir maintenance monotherapy. J Infect Dis. 2018;218(5): 688–697. doi: 10.1093/infdis/jiy176 29617822
34. Boender TS, Sigaloff KCE, McMahon JH, Kiertiburanakul S, Jordan MR, Barcarolo J, et al. Long-term Virological Outcomes of First-Line Antiretroviral Therapy for HIV-1 in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis. Clin Infect Dis. 2015;61(9):1453–61. doi: 10.1093/cid/civ556 26157050
35. Brooks K, Diero L, DeLong A, Balamane M, Reitsma M, Kemboi E, et al. Treatment failure and drug resistance in hiv-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. J Int AIDS Soc. 2016;19(1):1–10.
36. Castelnuovo B, Kiragga A, Mubiru F, Kambugu A, Kamya M, Reynolds SJ. First-line antiretroviral therapy durability in a 10-year cohort of naïve adults started on treatment in Uganda. J Int AIDS Soc. 2016;19(1):1–6.
37. Ntamatungiro AJ, Muri L, Glass TR, Erb S, Battegay M, Furrer H, et al. Strengthening HIV therapy and care in rural Tanzania affects rates of viral suppression. J Antimicrob Chemother. 2017;72(7):2069–74. doi: 10.1093/jac/dkx095 28387865
38. Shamu T, Chimbetete C, Shawarira–Bote S, Mudzviti T, Luthy R. Outcomes of an HIV cohort after a decade of comprehensive care at Newlands Clinic in Harare, Zimbabwe: TENART cohort. PLoS ONE. 2017;12(10):1–11.
39. Sovershaeva E, Shamu T, Wilsgaard T, Bandason T, Flægstad T, Katzenstein D, et al. Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe. Int J Infect Dis. 2019;78:65–71. doi: 10.1016/j.ijid.2018.10.019 30391420
40. Ndagijimana Ntwali JDD, Decroo T, Ribakare M, Kiromera A, Mugwaneza P, Nsanzimana S, et al. Viral load detection and management on first line ART in rural Rwanda. BMC Infect Dis. 2019;19(1):1–9. doi: 10.1186/s12879-018-3567-x
41. Labhardt ND, Ringera I, Lejone TI, Cheleboi M, Wagner S, Muhairwe J, et al. When patients fail UNAIDS’ last 90—The “failure cascade” beyond 90-90-90 in rural Lesotho, Southern Africa: A prospective cohort study: A. J Int AIDS Soc. 2017;20(1):1–10.
42. Tchouwa GF, Eymard-Duvernay S, Cournil A, Lamare N, Serrano L, Butel C, et al. Nationwide Estimates of Viral Load Suppression and Acquired HIV Drug Resistance in Cameroon. EClinicalMedicine. 2018;1:21–27. doi: 10.1016/j.eclinm.2018.06.005 31193678
43. Etoori D, Ciglenecki I, Ndlangamandla M, Edwards CG, Jobanputra K, Pasipamire M, et al. Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second-line switches in Swaziland. J Int AIDS Soc. 2018;21(10):1–8.
44. Fatti G, Grimwood A, Nachega JB, Nelson JA, LaSorda K, van Zyl G, et al. Better Virological Outcomes Among People Living With Human Immunodeficiency Virus (HIV) Initiating Early Antiretroviral Treatment (CD4 Counts ≥500 Cells/μL) in the HIV Prevention Trials Network 071 (PopART) Trial in South Africa. Clin Infect Dis. 2019. pii: ciz214. doi: 10.1093/cid/ciz214 Epub 2019 Mar 16. 30877753
45. Gaolathe Tendani, Wirth Kathleen E., Molly Pretorius Holme Joseph Makhema, Moyo Sikhulile, Chakalisa Unoda, et al. Botswana’s Progress Toward Achieving the 2020 UNAIDS 90–90–90 Antiretroviral Treatment and Virologic Suppression Goals: Results of a Population-Based Survey. Lancet HIV. 2016;3(5):1–21.
46. Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Kershberger B, et al. Factors Associated with Virological Failure and Suppression after Enhanced Adherence Counselling, in Children, Adolescents and Adults on Antiretroviral Therapy for HIV in Swaziland. PLoS ONE. 2015;10(2):e0116144. doi: 10.1371/journal.pone.0116144 25695494
47. Maskew M, Bor J, Hendrickson C, MacLeod W, Bärnighausen T, Pillay D, et al. Imputing HIV treatment start dates from routine laboratory data in South Africa: A validation study. BMC Health Serv Res. 2017;17(1):1–9. doi: 10.1186/s12913-016-1943-z
48. Fox MP, Bor J, Brennan AT, MacLeod WB, Maskew M, Stevens WS, et al. Estimating retention in HIV care accounting for patient transfers: A national laboratory cohort study in South Africa. PLoS Med. 2018;15(6):e1002589. doi: 10.1371/journal.pmed.1002589 29889844
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