Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria.
<h4>Background</h4>To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1(st)- and 2(nd)-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3(rd)-line (3 L) ART is needed. We aimed to...
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2013
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oai:doaj.org-article:359508ec00814e7bbff3759eaf8d7c242021-11-18T08:54:57ZAccumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria.1932-620310.1371/journal.pone.0073582https://doaj.org/article/359508ec00814e7bbff3759eaf8d7c242013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24069209/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1(st)- and 2(nd)-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3(rd)-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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.Holly E RawizzaBeth ChaplinSeema T MeloniKristin M DarinOluremi OlaitanKimberly K ScarsiChika K OnwuamahRosemary A AuduPhilippe R ChebuGodwin E ImadeProsper OkonkwoPhyllis J KankiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73582 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria. |
| description |
<h4>Background</h4>To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1(st)- and 2(nd)-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3(rd)-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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Holly E Rawizza |
| title |
Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria. |
| title_short |
Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria. |
| title_full |
Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria. |
| title_fullStr |
Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria. |
| title_full_unstemmed |
Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria. |
| title_sort |
accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in nigeria. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/359508ec00814e7bbff3759eaf8d7c24 |
| work_keys_str_mv |
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