Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria

Holly E. Rawizza, Beth Chaplin, Seema T. Meloni, Kristin M. Darin, Oluremi Olaitan, Kimberly K. Scarsi, Chika K. Onwuamah, Rosemary A. Audu, Philippe R. Chebu, Godwin E. Imade, Prosper Okonkwo, Phyllis J. Kanki

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background:To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and Findings:From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0-5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0-6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.Conclusions:This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.

Original languageEnglish (US)
Article numbere73582
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 16 2013

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Salvaging
Salvage Therapy
Nigeria
Peptide Hydrolases
proteinases
mutation
therapeutics
Lopinavir
Therapeutics
Protease Inhibitors
Switches
Mutation Accumulation
Mutation
Testing
viral load
proteinase inhibitors
Viral Load
Costs
Genotype
Guidelines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria. / Rawizza, Holly E.; Chaplin, Beth; Meloni, Seema T.; Darin, Kristin M.; Olaitan, Oluremi; Scarsi, Kimberly K.; Onwuamah, Chika K.; Audu, Rosemary A.; Chebu, Philippe R.; Imade, Godwin E.; Okonkwo, Prosper; Kanki, Phyllis J.

In: PloS one, Vol. 8, No. 9, e73582, 16.09.2013.

Research output: Contribution to journalArticle

Rawizza, HE, Chaplin, B, Meloni, ST, Darin, KM, Olaitan, O, Scarsi, KK, Onwuamah, CK, Audu, RA, Chebu, PR, Imade, GE, Okonkwo, P & Kanki, PJ 2013, 'Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria', PloS one, vol. 8, no. 9, e73582. https://doi.org/10.1371/journal.pone.0073582
Rawizza, Holly E. ; Chaplin, Beth ; Meloni, Seema T. ; Darin, Kristin M. ; Olaitan, Oluremi ; Scarsi, Kimberly K. ; Onwuamah, Chika K. ; Audu, Rosemary A. ; Chebu, Philippe R. ; Imade, Godwin E. ; Okonkwo, Prosper ; Kanki, Phyllis J. / Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria. In: PloS one. 2013 ; Vol. 8, No. 9.
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abstract = "Background:To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and Findings:From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0{\%}) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0-5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0-6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38{\%} of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63{\%}, with 5{\%} to darunavir.Conclusions:This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.",
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AU - Meloni, Seema T.

AU - Darin, Kristin M.

AU - Olaitan, Oluremi

AU - Scarsi, Kimberly K.

AU - Onwuamah, Chika K.

AU - Audu, Rosemary A.

AU - Chebu, Philippe R.

AU - Imade, Godwin E.

AU - Okonkwo, Prosper

AU - Kanki, Phyllis J.

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N2 - Background:To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and Findings:From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0-5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0-6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.Conclusions:This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.

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