Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa

Background: Tenofovir disoproxil fumarate (TDF) is increasingly available for patients infected with subtype C HIV-1. This subtype is reported to develop the principal TDF resistance mutation in the HIV reverse transcriptase, K65R, with greater propensity than other subtypes. We sought to describe K65R development during TDF use in a cohort of patients infected with subtype C HIV. Methods: Using a prospectively followed cohort with 6 monthly HIV RNA assays, we identiied virological failure (deined as an HIV RNA>1,000 copies/ml) during treatment that included TDF. Residual serum, stored at the time of the HIV RNA assay, was used for consensus sequencing and allele-speciic PCR. We assessed prevalence of resistance at failure during TDF-containing treatment and associated factors. Results: Among 1,682 patients on a TDF-containing regimen, 270 developed failure of which 40 were assessed for resistance. By sequencing, the K65R was identiied in 5 (12%), major non-nucleoside reverse transcriptase inhibitor mutations in 24 (57%) and the M184V/I in 12 (28%) patients. The K65R was associated with lower HIV RNA at failure (HIV RNA 3.3 versus 4.2 log ₁₀ copies/ml) and prior stavudine exposure. An additional ive patients had minority K65R populations identiied by allele-speciic PCR. Conclusions: These data suggest that the K65R prevalence at virological failure is moderately higher in our subtype C population than some non-subtype C HIV cohorts. However, we did not ind that the K65R was highly selected in HIV-1 subtype-C-infected patients with up to 6 months of failure of a TDF-containing regimen.