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    Longer-term effectiveness of protease-inhibitor-based second line antiretroviral therapy in four large sub-Saharan African clinics

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    Research article (578.2Kb)
    Date
    2019
    Author
    Sarfo, Fred S.
    Castelnuovo, Barbara
    Fanti, Iuri
    Feldt, Torsten
    Incardona, Francesca
    Kaiser, Rolf
    Lwanga, Isaac
    Marrone, Gaetano
    Sonnerborg, Anders
    Tufa, Tafese B.
    Zazzi, Maurizio
    De Luca, Andrea
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    Abstract
    Objectives: Data on the longer-term effectiveness of second line combination antiretroviral therapy (ART) in sub-Saharan Africa (SSA) are lacking. We sought to assess the probability and determinants of 2nd line ART failure in SSA. Methods: A retrospective, multi-center study of 2nd line ART initiated between 2005 and 2017 at four ART centers in Ethiopia, Ghana and Uganda. Main outcome measure was virologic failure (VF) defined as VL>1000 copies/ml after >6 months on 2nd line therapy. Predictors of VF and virologic re-suppression on 2nd line were evaluated using Cox Proportional Hazards and multivariable logistic regression models, respectively. Results: 2191 subjects started 2nd line therapy, 61.5% females. Switching from 1st line (56.4% NVP-based, 70.3% including thymidine-analogues) to 2nd line therapy occurred after mean of 4.1 years. 98.9% of patients started boosted PI with NRTI backbone (TDF+3TC/FTC 67.3%, AZT+3TC 18.5%, others 14.2%). There were 267 (12.0%) VF with a 5-year estimated probability of 15.0% (95% CI 13.2–16.9). Key determinants of VF were concomitant rifampicin use (aHR 2.50 [95% CI 1.54–4.05]) and clinical/immunological failure versus virologic failure as reason for switching therapy (aHR, 0.53 [0.33–0.86]). 138 of 267 (51.7%) subsequently achieved virologic re-suppression and predictors included HIV RNA levels at 2nd-line failure: +1 log higher aOR 0.59 [0.43–0.80], experiencing change within 2nd line ART before VF: aOR 0.17 [0.05– 0.56], and more recent calendar year of 2nd line initiation: aOR 0.85 [0.75–0.94]. Conclusions: The effectiveness of current 2nd line ART regimens in SSA is good but challenged by interactions with TB therapy
    URI
    https://doi.org/10.1016/j.jinf.2019.03.003
    http://hdl.handle.net/10570/14567
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