title: Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the Western Cape, South Africa.
abstract: Antiretroviral drug resistance in patients failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line combination antiretroviral treatment (ART) is influenced by: regimen choice, HIV-1 subtype, detection of and response to therapy failure. In order to describe resistance patterns by genotypic testing, at the time of first-line ART failure and to describe associations with having M184I/V, K65R, three or more thymidine analog mutations (TAMs) and etravirine (ETV) resistance, the prevalence of antiretroviral drug resistance associated mutations in a cross-sectional study, at two South African public health clinic settings, at the time of virologic failure (HIV-1 RNA load >400 copies/ml) are described. Also reported are associations of therapy choice, prolonged virologic failure, and concurrent HIV viral load and CD4 count with the presence of M184I/V, TAMs, K65R, and resistance to ETV. Of 167 adult patients with virologic failure on first-line ART, 28 (17%) had no resistance, 137 (82%) had NNRTI resistance, 101 (60%) M184I/V, 20 (12%) TAMs, of which 4 had 3 or more TAMs, and 7 (4%) had K65R, of which 6 were on D4T and one on AZT. A prolonged estimated period of failure was associated with having ≥3 TAMs. Patients treated with nevirapine (NVP) were more likely to have ETV resistance than those treated with efavirenz (EFV). Major protease inhibitor mutations were not detected. A delayed response to ART failure may risk accumulation of TAMs in patients on an NNRTI-based regimen. The use of NVP rather than EFV was associated with ETV resistance.
authors.affiliation: Division of Medical Virology, Stellenbosch University, Tygerberg, Cape Town, South Africa. guvz@sun.ac.za
authors.forename: Gert U
authors.initials: GU
authors.lastname: van Zyl
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Mathilda
authors.initials: M
authors.lastname: Claassen
authors.forename: Michele
authors.initials: M
authors.lastname: Zeier
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Preiser
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D009570:Nitriles; D011724:Pyridazines / Q000627:therapeutic use; D011743:Pyrimidines; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D015215:Zidovudine; D019829:Nevirapine; C098320:efavirenz