Longer-term effectiveness of protease-inhibitor-based second line antiretroviral therapy in four large sub-Saharan African clinics
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Date
2019Author
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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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