Antiretroviral therapy (ART) is pivotal for controlling HIV-1 infection through widescale treatment as prevention (TasP) and pre exposure prophylaxis (PreP). Tenofovir (TDF) is a key component of both approaches, though few data exist on regional burden of TDF resistance and the risk factors for its emergence. hylaxis (PreP). Tenofovir (TDF) is a key component of both approaches, though few data exist on regional burden of TDF resistance and the risk factors for its emergence.
We conducted an international multi-centre retrospective study of individuals undergoing genotyping following virological failure with 1st-line TDF-containing ART (with a 3TC or FTC plus either efavirenz (EFV) or nevirapine (NVP)). Meta-analysis and multiple logistic regression were used to identify covariates associated with emergence of TDF resistance (defined as presence of K65R/N or K70E/G/Q mutations).
Prevalence of TDF resistance amongst 1926 patients in 36 countries with treatment failure (as locally defined) was highest in low and middle income regions: 59.8% West/Central, 55.9% in Eastern and 55.2% in Southern Africa; 39% in Asia; 35.3% in Latin America, and lowest in high income regions: 18.8% in Western Europe and 22.6% in North America. Pre-ART CD4 cell count was associated with TDF resistance across regions (OR 1.49 (1.26-1.77) for CD4 count <100 cells/mm3 versus ≥100 cells/mm3). Use of 3TC versus FTC and NVP versus EFV increased the risk of tenofovir resistance [OR 1.49 (1.20 – 1.84)] and [OR 1.46 (1.28-1.67)] respectively across regions. The mean plasma viral load at virological failure was not different in the presence or absence of TDF associated mutations [145,700 copies/ml (SE 12,480) versus 133, 900 copies/ml (SE 16650), p=0.626].
TDF resistance emerges in a high proportion of patients who develop virological failure on a TDF-containing first line regimen in low-middle income regions. The risk of TDF resistance was also independently associated with a pre-ART CD4 count <100, the use of 3TC compared with FTC, and the use of EFV compared with NVP. Based on viral loads at faliure, TDF-resistant viruses have the potential to be as transmissible as viruses without TDF resistance.