High Tenofovir Failure Rates in an Emerging, Non-B Subtype HIV Epidemic

BACKGROUND: The WHO-recommended regimen for antiretrovirals (ARVs) is tenofovir (TDF) + lamivudine/emtricitabine (3TC/FTC) + efavirenz (EFV), based on demonstrated superiority of TDF+FTC+EFV over zidovudine (AZT) +FTC+ EFV in clinical trials. However, there are reports of increasing TDF resistance i...

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Detalles Bibliográficos
Autores principales: Salvana, Edsel Maurice, Schwem, Brian, Samonte, Genesis, Telan, Elizabeth, Tactacan-Abrenica, Rosario, Ching, Patrick, Mendoza, Kevin, Arevalo, Geraldine, Alejandria, Marissa, Leyritana, Katerina, Trinidad, Lyka, Penalosa, Christine, Lim, Jodor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Abstracts
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631214/
http://dx.doi.org/10.1093/ofid/ofx163.1081
Descripción
Sumario:BACKGROUND: The WHO-recommended regimen for antiretrovirals (ARVs) is tenofovir (TDF) + lamivudine/emtricitabine (3TC/FTC) + efavirenz (EFV), based on demonstrated superiority of TDF+FTC+EFV over zidovudine (AZT) +FTC+ EFV in clinical trials. However, there are reports of increasing TDF resistance in non-B subtypes. We have previously shown that HIV genotypes in the Philippines have shifted (https://idsa.confex.com/idsa/2014/webprogram/Paper45090.html) from B to CRF01_AE. We compared failure rates for ARVs during an acquired drug-resistance surveillance study. METHODS: We analyzed ARV data from a study with the Department of Health on treatment failure in Filipinos after one year of treatment. Institutional Board Review approval and informed consent were obtained. RESULTS: 513 adult patients from 3 national treatment hubs (Philippine General Hospital, San Lazaro Hospital, Vicente Sotto Memorial Medical Center) were enrolled and analyzed. Treatment failure (viral load>1000 copies/mL) at one year for specific regimens are summarized in Table 1. No baseline genotyping was available. 53 (10.3%) patients failed treatment. Genotypes among these were CRF01_AE (87%), B (11%) and C (2%). TDF-containing regimens had significantly higher failure rates (43/303;14.2%) than AZT-containing regimens (10/209;4.5%) (P < 0.001). Failure rates for NVP-based regimens (13/85;15.3%) vs. EFV-based regimens (40/424; 9.4%) were not significantly different (P = 0.1064). The most durable regimen (with >3 patients) was AZT+3TC+EFV, and the worst regimen was TDF+3TC+NVP (P < 0.001). Failure rates for TDF+3TC+EFV were significantly higher than for AZT+3TC+EFV (P = 0.0029). There was no significant difference in adherence (P = 0.5531). 53% of unsuppressed patients had a TDF-resistance mutation, compared with 8% for AZT (P < 0.001). CONCLUSION: TDF-containing regimens were associated with higher treatment failure rates in our CRF01_AE-predominant HIV epidemic. WHO recommendations for treatment may need be revisited for non-B subtypes. DISCLOSURES: E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium

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