Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa
Background. <br/>As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of prote...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Published: |
Oxford University Press
2016
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| _version_ | 1797051552482983936 |
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| author | Boender, T Hamers, R Ondoa, P Wellington, M Chimbetete, C Siwale, M Labib Maksimos, E Balinda, S Kityo, C Adeyemo, T Akanmu, A Mandaliya, K Botes, M Stevens, W Rinke de Wit, T Sigaloff, K |
| author_facet | Boender, T Hamers, R Ondoa, P Wellington, M Chimbetete, C Siwale, M Labib Maksimos, E Balinda, S Kityo, C Adeyemo, T Akanmu, A Mandaliya, K Botes, M Stevens, W Rinke de Wit, T Sigaloff, K |
| author_sort | Boender, T |
| collection | OXFORD |
| description | Background. <br/>As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. <br/><br/>Methods. <br/>HIV-1–infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. <br/><br/>Results.<br/> Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based (hazard ratio, 7.10; 95% confidence interval, 3.40–14.83; P < .001) or PI-based (7.59; 3.02–19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49–17.98; P < .001), and suboptimal adherence (3.05; 1.71–5.42; P = .025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. <br/><br/>Conclusions.<br/> Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary. |
| first_indexed | 2024-03-06T18:21:07Z |
| format | Journal article |
| id | oxford-uuid:065438e1-2f79-4667-9265-893404b4d9b6 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:21:07Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:065438e1-2f79-4667-9265-893404b4d9b62022-03-26T09:02:00ZProtease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan AfricaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:065438e1-2f79-4667-9265-893404b4d9b6Symplectic Elements at OxfordOxford University Press2016Boender, THamers, ROndoa, PWellington, MChimbetete, CSiwale, MLabib Maksimos, EBalinda, SKityo, CAdeyemo, TAkanmu, AMandaliya, KBotes, MStevens, WRinke de Wit, TSigaloff, KBackground. <br/>As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. <br/><br/>Methods. <br/>HIV-1–infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. <br/><br/>Results.<br/> Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based (hazard ratio, 7.10; 95% confidence interval, 3.40–14.83; P < .001) or PI-based (7.59; 3.02–19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49–17.98; P < .001), and suboptimal adherence (3.05; 1.71–5.42; P = .025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. <br/><br/>Conclusions.<br/> Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary. |
| spellingShingle | Boender, T Hamers, R Ondoa, P Wellington, M Chimbetete, C Siwale, M Labib Maksimos, E Balinda, S Kityo, C Adeyemo, T Akanmu, A Mandaliya, K Botes, M Stevens, W Rinke de Wit, T Sigaloff, K Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa |
| title | Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa |
| title_full | Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa |
| title_fullStr | Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa |
| title_full_unstemmed | Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa |
| title_short | Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa |
| title_sort | protease inhibitor resistance in the first 3 years of second line antiretroviral therapy for hiv 1 in sub saharan africa |
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