Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF)...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2018
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| _version_ | 1797097485970178048 |
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| author | Inzaule, S Kityo, C Siwale, M Akanmu, A Wellington, M De Jager, M Ive, P Mandaliya, K Stevens, W Boender, T Ondoa, P Sigaloff, K Naniche, D Rinke De Wit, T Hamers, R |
| author_facet | Inzaule, S Kityo, C Siwale, M Akanmu, A Wellington, M De Jager, M Ive, P Mandaliya, K Stevens, W Boender, T Ondoa, P Sigaloff, K Naniche, D Rinke De Wit, T Hamers, R |
| author_sort | Inzaule, S |
| collection | OXFORD |
| description | In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF) in a multicountry cohort of HIV-infected adults initiated on a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART. Multivariate logistic regression was used to assess the associations between PAU, PDR and VF (defined as viral load ≥400 cps/mL). Causal mediation analysis was used to assess the proportion of the effect of PAU on VF that could be eliminated by intervening on PDR. Of 2737 participants, 122 (4.5%) had a history of PAU. Participants with PAU had a 7.2-fold (95% CI 4.4-11.7) risk of carrying PDR and a 3.1-fold (95% CI 1.6-6.1) increased risk of VF, compared to antiretroviral-naïve participants. Controlling for PDR would eliminate nearly half the effect of PAU on the risk of VF. Patients with a history of PAU are at increased risk of ART failure, which is to a large extent attributable to PDR. These findings support the recent WHO recommendations for use of differentiated, non-NNRTI-based empiric first-line therapy in patients with PAU. |
| first_indexed | 2024-03-07T04:56:12Z |
| format | Journal article |
| id | oxford-uuid:d6afc2ae-194d-4f69-941e-8e716efafe60 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:56:12Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:d6afc2ae-194d-4f69-941e-8e716efafe602022-03-27T08:35:23ZPrevious antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistanceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d6afc2ae-194d-4f69-941e-8e716efafe60EnglishSymplectic Elements at OxfordSpringer Nature2018Inzaule, SKityo, CSiwale, MAkanmu, AWellington, MDe Jager, MIve, PMandaliya, KStevens, WBoender, TOndoa, PSigaloff, KNaniche, DRinke De Wit, THamers, RIn ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF) in a multicountry cohort of HIV-infected adults initiated on a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART. Multivariate logistic regression was used to assess the associations between PAU, PDR and VF (defined as viral load ≥400 cps/mL). Causal mediation analysis was used to assess the proportion of the effect of PAU on VF that could be eliminated by intervening on PDR. Of 2737 participants, 122 (4.5%) had a history of PAU. Participants with PAU had a 7.2-fold (95% CI 4.4-11.7) risk of carrying PDR and a 3.1-fold (95% CI 1.6-6.1) increased risk of VF, compared to antiretroviral-naïve participants. Controlling for PDR would eliminate nearly half the effect of PAU on the risk of VF. Patients with a history of PAU are at increased risk of ART failure, which is to a large extent attributable to PDR. These findings support the recent WHO recommendations for use of differentiated, non-NNRTI-based empiric first-line therapy in patients with PAU. |
| spellingShingle | Inzaule, S Kityo, C Siwale, M Akanmu, A Wellington, M De Jager, M Ive, P Mandaliya, K Stevens, W Boender, T Ondoa, P Sigaloff, K Naniche, D Rinke De Wit, T Hamers, R Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance |
| title | Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance |
| title_full | Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance |
| title_fullStr | Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance |
| title_full_unstemmed | Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance |
| title_short | Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance |
| title_sort | previous antiretroviral drug use compromises standard first line hiv therapy and is mediated through drug resistance |
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