title: Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa.
abstract: BACKGROUND: Emergence of HIV-1 drug resistance is at times an inevitable and anticipated consequence of antiretroviral therapy (ART) failure. We examined drug resistance patterns and virus re-suppression among subtype C-infected South African patients receiving first-line ART.  METHODS: Treatment records of 431 patients on NNRTI-containing regimens for a median of 45 months were analyzed. Patients with viral load (VL) >400 copies/mL were followed and drug resistance mutations (DRM) were re-assessed. Associations between clinical/demographic measures and drug resistance/virologic outcomes were examined using Fisher exact and ordinal and logistic regression.  RESULTS: Ten percent of patients (43/431) were viremic at enrollment (98% previously suppressed); sequences were obtained from 38/43. Of those, 82% had 1-7 DRM. In bivariate analysis remote exposure to single-dose nevirapine or prior ART; higher CD4 counts; lower VL; and >6 months of virologic failure were significantly associated with number of DRM. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48%) re-suppressed, six with K103N and three with M184V. Thirteen (52%) had continued virologic failure which was significantly associated with detectable VL>6 months prior to enrollment and number of DRM.  CONCLUSION: Among these HIV-1 subtype C-infected patients, DRM numbers and patterns were associated with prior exposure to sub-optimal ART, adherence and duration of virologic failure. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. In resource-limited settings, where genotyping and alternative drug options are unavailable, continuing first-line treatment, reinforcing adherence and regular virologic monitoring may be effective even after virologic failure.
authors.affiliation: Division of Global Health (IHCAR), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ziad
authors.initials: Z
authors.lastname: El-Khatib
authors.forename: Allison K
authors.initials: AK
authors.lastname: Delong
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
authors.forename: Anna Mia
authors.initials: AM
authors.lastname: Ekstrom
authors.forename: Johanna
authors.initials: J
authors.lastname: Ledwaba
authors.forename: Lerato
authors.initials: L
authors.lastname: Mohapi
authors.forename: Fatima
authors.initials: F
authors.lastname: Laher
authors.forename: Max
authors.initials: M
authors.lastname: Petzold
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Rami
authors.initials: R
authors.lastname: Kantor