Abstract:
Abstract
Introduction
: Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its
incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a
cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment
programme in western Kenya.
Methods
: We determined viral load (VL), drug resistance and their correlates in patients on
]
six months of tenofovir-based first-
line ART. Based on enrolled patients’ characteristics, we described these measures in those with (prior ART group) and without
(tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher’s exact tests.
Results
: Among 333 participants (55% female; median age 41 years; median CD4 336 cells/
m
L), detectable (
40 copies/mL) VL
was found in 18%, and VL
1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher
in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with
VL
40 copies/mL; 15% vs. 1% with VL
1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4
values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL
40 copies/mL
(69% subtype A), any resistance was found in 89% and dual-class res
istance in 83%. Tenofovir signature mutation K65R occurred in
71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and
more resistance mutations.
Conclusions
: In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high
suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance
levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL
monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized
resistance testing to design effective subsequent regimens
