Very high levels of drug resistance seen in people experiencing first-line antiretroviral therapy failure in Kenya
A cross-sectional survey of viral load in patients attending the largest clinic providing antiretroviral therapy (ART) in Kenya has shown that after an average of nearly two years on first-line, tenofovir-based ART, 76% maintained a viral load under 40 copies/ml and 85% under 1000 copies/ml, the World Health Organization threshold for significant clinical and transmission consequences.
The study also found that tenofovir-based ART was more successful in patients who had been on previous ART and switched to the present regimen; 93% of them had viral loads under 40% and 99% under 1000 copies/ml.
However, the study found extremely high rates of significant drug resistance in those whose viral load was detectable. Eighty-nine per cent of first-line patients tested had mutations conferring resistance to drugs in at least one class of antiretrovirals and 83% to two or more classes. The K65R mutation, which confers resistance to all other drugs of the NRTI class except zidovudine, was present in more than two-thirds of patients – considerably in excess of its prevalence in patients tested for resistance in higher-income settings. The resistance patterns seen effectively ruled out future treatment success with all available NNRTI drugs as well as all NRTI drugs except zidovudine (AZT).
The high resistance rates seen underline the importance of adopting viral load testing more widely in low-income settings, as the biggest contributor to resistance was that patients may have been on failing therapy for up to two years before failure was detected.
The fact that average CD4 cell counts were lower in patients failing ART and even lower in patients with viral loads high enough to test for resistance show that while CD4 monitoring may still have a part to play in flagging up treatment failure, the lack of a means to detect virological failure has real clinical consequences.