Abstract:
Introduction: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya
are limited. Collection of non-plasma analytes may provide additional resistance information.
Methods: We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired
resistance upon first-line failure by the IAS_USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH),
a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasmaspots
(DPS), ViveSTTM-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence
concordance.
Results: Among 122 patients, 62 were treatment-naı¨ve and 60 treatment-experienced; 61% were female, median age 35 years,
median CD4 182 cells/mL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for
107/122 (88%) patients, 58/62 (94%) treatment-naı¨ve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted
DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42
(12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping
time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and
7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76%
dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence
patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92%
in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was
1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation
was identified in plasma and 22 in STP (pB0.05). Discordance was inversely significantly related to VL for DBS.
Conclusions: In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted
resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns.
Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.