Findings from a HIV clinic in a rural district hospital in coastal Kenya suggest that one in every four adults on first-line antiretroviral regimen for an average of 14 months had VF, with half of those with VF harboring at least one HIV resistance-associated mutation. The most prevalent mutations observed confer high-level resistance to NRTIs (specifically lamivudine, in the case of the M184V mutation) and NNRTIs (specifically nevirapine and efavirenz, in the case of the K103N/S mutation and the Y181C/Y/I/V mutation). These results are consistent with findings from systematic reviews of studies on virological efficacy and drug resistance from other resource limited settings [15, 26]. The non-complex resistance patterns observed could possibly indicate an advantage of the current recommended first-line regimen in this setting.
The WHO recommends use of drug-refill data as an early warning indicator (EWI) of HIV treatment failure and drug resistance . Recent EWI analyses on prospective HIVDR data from 6 African countries suggest an advantage of MPR over on-time drug pick-up in identifying participants at risk for developing HIV drug resistance . For this reason, MPR was used and indeed identified as a practical alternative parameter for assessing adherence, with strong correlation with both VF and ADR in this setting. Similar findings have also been reported elsewhere [19, 29–31].
The current study also indicated younger age as a strong risk factor for both HIV-1 VF and ADR. In fact, half of all participants aged 15–24 years had VF, while two in every five had acquired at least one drug resistant strain. Data from a developed setting suggests that the youth face a complex myriad of challenges including peer-related stigma, disclosure, adherence, sexual, reproductive and gender health concerns . If applicable, then these challenges may indirectly contribute to the high burden of virological treatment failure and ADR in our setting.
Higher viral load was strongly associated with ADR, which is consistent with literature . Of interest however, is the finding that only half of participants with VF had detectable ADR. Indeed, if the Kenyan national recommendation of ≥1000 copies/ml was used to suggest VF in this study , and assuming sustained viral replication, then a fifth of the participants would have VF. Of these, only 58% had detectable ADR mutations. These data may therefore suggest that up to 42% of participants would have potentially been switched to the more expensive 2nd line regimen prematurely or unnecessarily, thus exhausting and limiting treatment options. This is especially risky in this setting where the only currently recommended second line option is the bPIs, with costs prohibiting the range of other potential alternative regimens.
The findings of this study should be interpreted in light of several limitations. Firstly, the cross-sectional study design and the one-off sampling strategy warrant caution in the interpretation of our findings, as follow up samples were not available to confirm VF. Consequently, blips in viral load cannot be ruled out . It is acknowledged that occasionally, viral blips can occur even during effective treatment [35, 36]. This may have resulted to an overestimation of the true burden of VF in this population. In addition, focusing on participants with a median ART follow up duration of more than a year potentially excludes those who may have died or were lost to follow-up within a year of ART due to treatment failure. This may have resulted in an underestimation of the true burden of VF and ADR in this population.
Secondly, it may be argued that the participants may not have achieved virological suppression in the first place, even after being on ART for more than 6 months. This may possibly be attributed to the effect of persisting HIV-1 primary or transmitted resistance mutations, which have been reported to be on the increase in some parts of sSA [37, 38]. Transmitted resistant strains have been shown to contribute to VF in clients on ART [39–41]. However, our concurrent data suggest low levels (<5%) of transmitted drug resistance in this rural coastal Kenyan population .
Lastly, stigma, disclosure, sexual orientation, reproductive health and gender issues are potential concerns that may contribute to the burden of VF and ADR, especially among the young adults in this setting. Data on these factors were not captured and hence not considered in the analyses.