High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania – A prospective cohort study

Autoři: Rahel E. Bircher aff001;  Alex J. Ntamatungiro aff001;  Tracy R. Glass aff002;  Dorcas Mnzava aff001;  Amina Nyuri aff001;  Herry Mapesi aff001;  Daniel H. Paris aff002;  Manuel Battegay aff003;  Thomas Klimkait aff004;  Maja Weisser aff001
Působiště autorů: Ifakara Health Institute, Ifakara, Tanzania aff001;  Swiss Tropical and Public Health Institute, Basel, Switzerland aff002;  University of Basel, Basel, Switzerland aff003;  Molecular Virology, Department Biomedicine Petersplatz, University of Basel, Basel, Switzerland aff004;  St. Francis Referral Hospital, Ifakara, Tanzania aff005;  Departments of Medicine and Clinical Research, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227600



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.


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.


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.


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.

Klíčová slova:

Antimicrobial resistance – Antiretroviral therapy – Drug therapy – HIV – Protease inhibitor therapy – Protease inhibitors – Tanzania – Viral load


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