Our data confirm the reported association of older age and neuropathy. D-Pantothenic acid sodium Whereas most previous studies have reported advanced HIV stage as a risk factor for neuropathy, we observed an increased risk associated with low baseline haemoglobin. Possibly, this is merely a reflection of advanced disease at ART initiation. Alternatively, recent studies have observed the strong and independent prognostic information contained in both baseline and time-updated haemoglobin levels, even after adjustment for CD4 cell count values. In contrast with a South African study, we did not find an association of neuropathy with TB treatment. Possible reasons for this could include differences in analytical approach, management of toxicity or timing of ART initiation for patients on TB treatment. With regards to SH/LA, the association with the use of tuberculosis treatment is somehow surprising and has not been reported yet. In one case-control study, Oxytocin (Syntocinon) efavirenz was identified as a risk factor for lactic acidosis. Whether this could be the mechanism behind our observed association with tuberculosis treatment, albeit not identified in multivariate analysis, remains to be determined. Alternatively, rapid weight gain after ART initiation, identified as a risk factor for lactic acidosis in a South African study, might be implicated for patients on tuberculosis treatment. Finally, it needs to be pointed out that TB treatment and the use of EFV are closely related variables. Although no clear problem of collinearity was detected during analysis, the problem cannot be entirely ruled out. Cost has been a major reason for the ongoing use of D4Tcontaining ART in LMIC. Despite recent cost reductions, tenofovir-based regimens are still more than twice as expensive in terms of drug costs. In Cambodia, the low cost of D4T is a key argument for maintaining this drug within first line treatment regimens for the next years to come. Our data suggest that the cost-saving effect with D4T-use is limited in time, given the high long-term rates of D4T-replacement. Moreover, its ongoing use continues to expose patients to drug toxicity, with all its negative implications. Whereas our data reinforce the need to phase-out D4T to better tolerated regimens in LMIC, it is clear that this is a major operational undertaking that should be implemented in a phased and controlled manner. In this regard, our experience could be of interest for national programs willing to implement a gradual phasing-out of D4T. By combining patient education, close monitoring for D4T-toxicities, integrating the patient��s perception and applying a low threshold for D4T-replacement, a gradual phasing-out of D4T can be expected. Additionally, the occurrence of toxicity could be significantly reduced by prioritizing those at highest risk of D4T toxicity, based on the risk factors identified. Importantly, patient support relative to a uniform and quick D4T replacement strategy might be enhanced with this more targeted approach.