Open AccessHigh failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania – A prospective cohort study
Author(s) -
Rahel Bircher,
Alex Ntamatungiro,
Tracy R. Glass,
Dorcas Mnzava,
Amiyuri,
Herry Mapesi,
Daniel Paris,
Manuel Battegay,
Thomas Klimkait,
Maja Weisser
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0227600
Subject(s) - protease inhibitor (pharmacology) , viral load , protease , drug resistance , regimen , medicine , cohort study , prospective cohort study , hiv drug resistance , virology , biology , human immunodeficiency virus (hiv) , antiretroviral therapy , microbiology and biotechnology , biochemistry , enzyme
Background Poor adherence to antiretroviral drugs and viral resistance are the main drivers of treatment failure in HIV-infected patients. In sub-Saharan Africa, avoidance of treatment failure on second-line protease inhibitor therapy is critical as treatment options are limited. Methods In the prospective observational study of the Kilombero & Ulanga Antiretroviral Cohort in rural Tanzania, we assessed virologic failure (viral load ≥1,000 copies/mL) and drug resistance mutations in bio-banked plasma samples 6–12 months after initiation of a protease inhibitor-based treatment regimen. Additionally, viral load was measured before start of protease inhibitor, a second time between 1–5 years after start, and at suspected treatment failure in patients with available bio-banked samples. We performed resistance testing if viral load was ≥1000 copies/ml. Risk factors for virologic failure were analyzed using logistic regression. Results In total, 252 patients were included; of those 56% were female and 21% children. Virologic failure occurred 6–12 months after the start of a protease inhibitor in 26/199 (13.1%) of adults and 7/53 of children (13.2%). The prevalence of virologic failure did not change over time. Nucleoside reverse transcriptase inhibitors drug resistance mutation testing performed at 6–12 months showed a positive signal in only 9/16 adults. No cases of resistance mutations for protease inhibitors were seen at this time. In samples taken between 1–5 years protease inhibitor resistance was demonstrated in 2/7 adults. In adult samples before protease inhibitor start, resistance to nucleoside reverse transcriptase inhibitors was detected in 30/41, and to non-nucleoside reverse-transcriptase inhibitors in 35/41 patients. In 15/16 pediatric samples, resistance to both drug classes but not for protease inhibitors was present. Conclusion Our study confirms high early failure rates in adults and children treated with protease inhibitors, even in the absence of protease inhibitors resistance mutations, suggesting an urgent need for adherence support in this setting.