Skip to main content
Top
Published in: AIDS Research and Therapy 1/2012

Open Access 01-12-2012 | Research

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

Authors: Thanyawee Puthanakit, Gonzague Jourdain, Piyarat Suntarattiwong, Kulkanya Chokephaibulkit, Umaporn Siangphoe, Tulathip Suwanlerk, Wasana Prasitsuebsai, Virat Sirisanthana, Pope Kosalaraksa, Witaya Petdachai, Rawiwan Hansudewechakul, Naris Waranawat, Jintanat Ananworanich, the HIV-NAT 086 study team

Published in: AIDS Research and Therapy | Issue 1/2012

Login to get access

Abstract

Background

Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens.

Methods

A retrospective chart review was conducted at 8 Thai sites of children who switched to PI –based regimens due to failure of NNRTI –based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks.

Results

Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002).

Conclusion

Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ciaranello AL, Chang Y, Margulis AV, Bernstein A, Bassett IV, Losina E: Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Clin Infect Dis. 2009 Dec 15, 49 (12): 1915-27. 10.1086/648079.PubMedCentralCrossRefPubMed Ciaranello AL, Chang Y, Margulis AV, Bernstein A, Bassett IV, Losina E: Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Clin Infect Dis. 2009 Dec 15, 49 (12): 1915-27. 10.1086/648079.PubMedCentralCrossRefPubMed
2.
go back to reference Kariminia A, Chokephaibulkit K, Pang J, Lumbiganon P, Hansudewechakul R, Amin J: Cohort profile: the TREAT Asia pediatric HIV observational database. Int J Epidemiol. 2011 Feb, 40 (1): 15-24. 10.1093/ije/dyp358.PubMedCentralCrossRefPubMed Kariminia A, Chokephaibulkit K, Pang J, Lumbiganon P, Hansudewechakul R, Amin J: Cohort profile: the TREAT Asia pediatric HIV observational database. Int J Epidemiol. 2011 Feb, 40 (1): 15-24. 10.1093/ije/dyp358.PubMedCentralCrossRefPubMed
3.
go back to reference Puthanakit T, Oberdorfer A, Akarathum N, Kanjanavanit S, Wannarit P, Sirisanthana T: Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand's National Access to Antiretroviral Program. Clin Infect Dis. 2005 Jul 1, 41 (1): 100-7. 10.1086/430714.CrossRefPubMed Puthanakit T, Oberdorfer A, Akarathum N, Kanjanavanit S, Wannarit P, Sirisanthana T: Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand's National Access to Antiretroviral Program. Clin Infect Dis. 2005 Jul 1, 41 (1): 100-7. 10.1086/430714.CrossRefPubMed
4.
go back to reference Kamya MR, Mayanja-Kizza H, Kambugu A, Bakeera-Kitaka S, Semitala F, Mwebaze-Songa P: Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. Journal of acquired immune deficiency syndromes. 2007, 46 (2): 187-93. 10.1097/QAI.0b013e31814278c0CrossRefPubMed Kamya MR, Mayanja-Kizza H, Kambugu A, Bakeera-Kitaka S, Semitala F, Mwebaze-Songa P: Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. Journal of acquired immune deficiency syndromes. 2007, 46 (2): 187-93. 10.1097/QAI.0b013e31814278c0CrossRefPubMed
5.
go back to reference Janssens B, Raleigh B, Soeung S, Akao K, Te V, Gupta J: Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia. Pediatrics. 2007 Nov, 120 (5): e1134-40. 10.1542/peds.2006-3503.CrossRefPubMed Janssens B, Raleigh B, Soeung S, Akao K, Te V, Gupta J: Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia. Pediatrics. 2007 Nov, 120 (5): e1134-40. 10.1542/peds.2006-3503.CrossRefPubMed
6.
go back to reference Jaspan HB, Berrisford AE, Boulle AM: Two-year outcomes of children on non-nucleoside reverse transcriptase inhibitor and protease inhibitor regimens in a South African pediatric antiretroviral program. Pediatr Infect Dis J. 2008, 27 (11): 993-8. 10.1097/INF.0b013e31817acf7bCrossRefPubMed Jaspan HB, Berrisford AE, Boulle AM: Two-year outcomes of children on non-nucleoside reverse transcriptase inhibitor and protease inhibitor regimens in a South African pediatric antiretroviral program. Pediatr Infect Dis J. 2008, 27 (11): 993-8. 10.1097/INF.0b013e31817acf7bCrossRefPubMed
7.
go back to reference Prasitsuebsai W, Bowen AC, Pang J, Hesp C, Kariminia A, Sohn AH: Pediatric HIV clinical care resources and management practices in Asia: a regional survey of the TREAT Asia pediatric network. AIDS Patient Care STDS. 2010, 24 (2): 127-31. 10.1089/apc.2009.0224PubMedCentralCrossRefPubMed Prasitsuebsai W, Bowen AC, Pang J, Hesp C, Kariminia A, Sohn AH: Pediatric HIV clinical care resources and management practices in Asia: a regional survey of the TREAT Asia pediatric network. AIDS Patient Care STDS. 2010, 24 (2): 127-31. 10.1089/apc.2009.0224PubMedCentralCrossRefPubMed
9.
go back to reference Working Group on Antiretroviral Therapy and Medical Managment of HIV-infected children: Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, February 23, 2009. 2009,http://AIDSinfo.nih.gov/, US Department of Health and Human Services: Access, Working Group on Antiretroviral Therapy and Medical Managment of HIV-infected children: Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, February 23, 2009. 2009,http://​AIDSinfo.​nih.​gov/​, US Department of Health and Human Services: Access,
10.
go back to reference Resino S, Bellon JM, Ramos JT, Navarro ML, Martin-Fontelos P, Cabrero E: Salvage lopinavir-ritonavir therapy in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2004, 23 (10): 923-30. 10.1097/01.inf.0000142170.52155.7fCrossRefPubMed Resino S, Bellon JM, Ramos JT, Navarro ML, Martin-Fontelos P, Cabrero E: Salvage lopinavir-ritonavir therapy in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2004, 23 (10): 923-30. 10.1097/01.inf.0000142170.52155.7fCrossRefPubMed
11.
go back to reference Sungkanuparph S, Manosuthi W, Kiertiburanakul S, Piyavong B, Chumpathat N, Chantratita W: Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. Clin Infect Dis. 2007 Feb 1, 44 (3): 447-52. 10.1086/510745.CrossRefPubMed Sungkanuparph S, Manosuthi W, Kiertiburanakul S, Piyavong B, Chumpathat N, Chantratita W: Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. Clin Infect Dis. 2007 Feb 1, 44 (3): 447-52. 10.1086/510745.CrossRefPubMed
12.
go back to reference Jittamala P, Puthanakit T, Chaiinseeard S, Sirisanthana V: Predictors of virologic failure and genotypic resistance mutation patterns in thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Pediatr Infect Dis J. 2009, 28 (9): 826-30. 10.1097/INF.0b013e3181a458f9CrossRefPubMed Jittamala P, Puthanakit T, Chaiinseeard S, Sirisanthana V: Predictors of virologic failure and genotypic resistance mutation patterns in thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Pediatr Infect Dis J. 2009, 28 (9): 826-30. 10.1097/INF.0b013e3181a458f9CrossRefPubMed
13.
go back to reference Puthanakit T, Jourdain G, Hongsiriwon S, Suntarattiwong P, Chokephaibulkit K, Sirisanthana V: HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy. HIV medicine. 2010, 11 (9): 565-72. 10.1111/j.1468-1293.2010.00828.xCrossRefPubMed Puthanakit T, Jourdain G, Hongsiriwon S, Suntarattiwong P, Chokephaibulkit K, Sirisanthana V: HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy. HIV medicine. 2010, 11 (9): 565-72. 10.1111/j.1468-1293.2010.00828.xCrossRefPubMed
14.
go back to reference Bunupuradah T, van der Lugt J, Kosalaraksa P, Engchanil C, Boonrak P, Puthanakit T: Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks. Antivir Ther. 2009, 14 (2): 241-8.PubMed Bunupuradah T, van der Lugt J, Kosalaraksa P, Engchanil C, Boonrak P, Puthanakit T: Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks. Antivir Ther. 2009, 14 (2): 241-8.PubMed
15.
go back to reference Thai Ministry of Public Health: Thai National guideline for managment of HIV-infected children and adults. 2004, ISBN 974-297-2982 Thai Ministry of Public Health: Thai National guideline for managment of HIV-infected children and adults. 2004, ISBN 974-297-2982
16.
go back to reference Sirivichayakul S, Ruxrungtham K, Ungsedhapand C, Techasathit W, Ubolyam S, Chuenyam T: Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. AIDS (London, England). 2003, 17 (13): 1889-96. 10.1097/00002030-200309050-00007.CrossRef Sirivichayakul S, Ruxrungtham K, Ungsedhapand C, Techasathit W, Ubolyam S, Chuenyam T: Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. AIDS (London, England). 2003, 17 (13): 1889-96. 10.1097/00002030-200309050-00007.CrossRef
17.
go back to reference World Health Organization: Antiretroviral therapy for HIV infection in infants and children: towards universal access. 2010, Recommendations for a public health approach World Health Organization: Antiretroviral therapy for HIV infection in infants and children: towards universal access. 2010, Recommendations for a public health approach
18.
go back to reference Kline MW, Rugina S, Ilie M, Matusa RF, Schweitzer AM, Calles NR: Long-term follow-up of 414 HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy. Pediatrics. 2007 May, 119 (5): e1116-20. 10.1542/peds.2006-2802.CrossRefPubMed Kline MW, Rugina S, Ilie M, Matusa RF, Schweitzer AM, Calles NR: Long-term follow-up of 414 HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy. Pediatrics. 2007 May, 119 (5): e1116-20. 10.1542/peds.2006-2802.CrossRefPubMed
19.
go back to reference De Luca M, Miccinesi G, Chiappini E, Zappa M, Galli L, De Martino M: Different kinetics of immunologic recovery using nelfinavir or lopinavir/ritonavir-based regimens in children with perinatal HIV-1 infection. Int J Immunopathol Pharmacol. 2005, 18 (4): 729-35.PubMed De Luca M, Miccinesi G, Chiappini E, Zappa M, Galli L, De Martino M: Different kinetics of immunologic recovery using nelfinavir or lopinavir/ritonavir-based regimens in children with perinatal HIV-1 infection. Int J Immunopathol Pharmacol. 2005, 18 (4): 729-35.PubMed
20.
go back to reference Hosseinipour MC, Kumwenda JJ, Weigel R, Brown LB, Mzinganjira D, Mhango B: Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline. HIV medicine. 2010, 11 (8): 510-8.PubMed Hosseinipour MC, Kumwenda JJ, Weigel R, Brown LB, Mzinganjira D, Mhango B: Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline. HIV medicine. 2010, 11 (8): 510-8.PubMed
21.
go back to reference Kosalaraksa P, Bunupuradah T, Engchanil C, Boonrak P, Intasan J, Lumbiganon P: Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J. 2008, 27 (7): 623-8. 10.1097/INF.0b013e31816b4539CrossRefPubMed Kosalaraksa P, Bunupuradah T, Engchanil C, Boonrak P, Intasan J, Lumbiganon P: Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J. 2008, 27 (7): 623-8. 10.1097/INF.0b013e31816b4539CrossRefPubMed
22.
go back to reference Chetchotisakd P, Anunnatsiri S, Mootsikapun P, Kiertiburanakul S, Anekthananon T, Bowonwatanuwong C: Efficacy and tolerability of a double boosted protease inhibitor (lopinavir + saquinavir/ritonavir) regimen in HIV-infected patients who failed treatment with nonnucleoside reverse transcriptase inhibitors. HIV medicine. 2007, 8 (8): 529-35. 10.1111/j.1468-1293.2007.00506.xCrossRefPubMed Chetchotisakd P, Anunnatsiri S, Mootsikapun P, Kiertiburanakul S, Anekthananon T, Bowonwatanuwong C: Efficacy and tolerability of a double boosted protease inhibitor (lopinavir + saquinavir/ritonavir) regimen in HIV-infected patients who failed treatment with nonnucleoside reverse transcriptase inhibitors. HIV medicine. 2007, 8 (8): 529-35. 10.1111/j.1468-1293.2007.00506.xCrossRefPubMed
23.
go back to reference Bunupuradah T, Chetchotisakd P, Ananworanich J, Munsakul W, Jirajariyavej S, Kantipong P: A randomized comparison of second-line lopinavir/ritonavir monotherapy vs. tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI-regimens: the HIV STAR study. Antivir Ther. 2012, Jul 2 [Epub ahead of print] Bunupuradah T, Chetchotisakd P, Ananworanich J, Munsakul W, Jirajariyavej S, Kantipong P: A randomized comparison of second-line lopinavir/ritonavir monotherapy vs. tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI-regimens: the HIV STAR study. Antivir Ther. 2012, Jul 2 [Epub ahead of print]
24.
go back to reference Manosuthi W, Kiertiburanakul S, Amornnimit W, Prasithsirikul W, Thongyen S, Nilkamhang S: Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. AIDS Res Ther. 2009, 6: 30- 10.1186/1742-6405-6-30PubMedCentralCrossRefPubMed Manosuthi W, Kiertiburanakul S, Amornnimit W, Prasithsirikul W, Thongyen S, Nilkamhang S: Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. AIDS Res Ther. 2009, 6: 30- 10.1186/1742-6405-6-30PubMedCentralCrossRefPubMed
25.
go back to reference Perez-Valero I, Arribas JR: Protease inhibitor monotherapy. Curr Opin Infect Dis. 24 (1): 7-11. 10.1371/journal.pone.0022003CrossRefPubMed Perez-Valero I, Arribas JR: Protease inhibitor monotherapy. Curr Opin Infect Dis. 24 (1): 7-11. 10.1371/journal.pone.0022003CrossRefPubMed
26.
go back to reference Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M: Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis. PLoS One. 2011, 6 (7): e22003- 10.1371/journal.pone.0022003PubMedCentralCrossRefPubMed Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M: Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis. PLoS One. 2011, 6 (7): e22003- 10.1371/journal.pone.0022003PubMedCentralCrossRefPubMed
28.
go back to reference Babiker A, Castro nee Green H, Compagnucci A, Fiscus S, Giaquinto C, Gibb DM: First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. Lancet Infect Dis. 2011, 273-83. 4 Babiker A, Castro nee Green H, Compagnucci A, Fiscus S, Giaquinto C, Gibb DM: First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. Lancet Infect Dis. 2011, 273-83. 4
Metadata
Title
High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting
Authors
Thanyawee Puthanakit
Gonzague Jourdain
Piyarat Suntarattiwong
Kulkanya Chokephaibulkit
Umaporn Siangphoe
Tulathip Suwanlerk
Wasana Prasitsuebsai
Virat Sirisanthana
Pope Kosalaraksa
Witaya Petdachai
Rawiwan Hansudewechakul
Naris Waranawat
Jintanat Ananworanich
the HIV-NAT 086 study team
Publication date
01-12-2012
Publisher
BioMed Central
Published in
AIDS Research and Therapy / Issue 1/2012
Electronic ISSN: 1742-6405
DOI
https://doi.org/10.1186/1742-6405-9-20

Other articles of this Issue 1/2012

AIDS Research and Therapy 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.