AIDS Research and Treatment The absence of macrocytosis was associated with viro- logical failure, as all the patients were on AZT- or d4T- based regimens. The association was strong in previously ARV-na¨ıve patients and persisted in multivariate analysis. In Cambodia, as well as in many other low- to middle-income countries, AZT and d4T are the most widely used NRTIs, in keeping with WHO recommendations. MCV was deter- mined during standard automated blood analyses, which are widely available in many district hospitals in Cambodia. This parameter might thus be used in combination with clinical and immunological criteria to monitor HAART exposure and eﬃcacy. Forty percent of our patients had taken dual NRTI therapy or a ﬁxed dose combination of D4T/3TC/NVP before entry to the ESTHER program, and the eﬃcacy of the study regimens was lower in these patients than in previously ARV-na¨ıve patients. Self-funded treatment in the private sector was signiﬁcantly associated with subsequent virological failure, even after adjustment for other factors [37]. This was conﬁrmed by our logistic regression analysis. These patients probably had NRTI and/or NNRTI resistance mutations (data not shown), and subsequent HAART was often ineﬀective despite good adherence. Resistance to NNRTIs and NRTIs is the most important issue in low- to middle-income countries, where access to protease inhibitors is limited. WHO-approved ﬁrst-line HAART must be maintained as long as possible, and the identiﬁcation of patients at risk of resistance must be a priority. Unfortunately, access to viral load assay and genotypic resistance tests is currently limited. As self-report questionnaires may lack accuracy and as drug monitoring is diﬃcult to implement, MCV could be an interesting alternative marker of adherence. Viral load assay could be added if MCV results suggest poor adherence. 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