4 AIDS Research and Treatment Table 3: Association between the four measures of adherence and virological failure in the previously HAART-na¨ıve population. Self-report questionnaire (all three items)∗ 100% adherent At least one missed HAART dose Visual analog scale∗ 10 9 <9 Antiretroviral drug concentrations (ng/mL) ≥1000 for EFV or ≥3000 for NVP <1000 for EFV or <3000 for NVP Macrocytosis (MCV ≥ 100 fL)∗∗ Yes No Self-report questionnaire and macrocytosis 100% adherent At least one mistake Self-report questionnaire and drug assays 100% adherent At least one mistake N 134 22 110 39 7 149 9 141 14 121 32 129 27 Virological failure: N (%) 22 (16.4) 8 (36.4) 20 (18.1) 8 (20.5) 2 (28.6) 24 (16.1) 6 (66.7) 23 (16.3) 7 (50) 18 (14.9) 12 (37.5) 20 (15.5) 10 (37) OR [95% CI] 1 2.91 [1.09–7.76] 1 1.16 [0.46–2.90] 1.8 [0.32–9.95] 1 10.42 [2.43–44.54] 1 5.13 [1.64–16.02] 1 3.43 [1.43–8.22] 1 3.20 [1.28–8] P .034 .78 .002 .007 .006 .015 OR: odds ratio; CI: conﬁdence interval, ∗Available for 156 patients, ∗∗Available for 155 patients. Table 4: Multivariate logistic regression: factors associated with virological failure (N = 250). Sex Female Male Previously treated patients No Yes Self-report questionnaire 100% adherent At least one mistake Macrocytosis Yes No Plasma drug concentrations ≥1000 for EFV or ≥3000 for NVP <1000 for EFV or <3000 for NVP OR: odds ratio; CI: conﬁdence interval. OR [95% CI] 1 0.59 [0.32–1.09] 1 3.98 [2.15–7.36] 1 0.88 [0.36–2.14] 1 3.09 [1.17–8.18] 1 10.46 [3.06–35.78] P .094 .77 .023 <.0001 <.0001 procurement and distribution practices avoided drug supply disruption. Both points have been shown to be a signiﬁcant cause of drug resistance and ARV failure in Uganda [34]. Third, the patients received therapeutic education aimed at improving adherence [19]. The patients had been following this program for between three and six months before being evaluated for virological outcome and simultaneously, for adherence. In low- to middle-income countries, where access to viral load assays is limited, HAART eﬃcacy is monitored by using clinical and immunological criteria that have relatively low positive predictive value for virological failure [35, 36]. In order to improve the prediction of virological eﬃcacy, we evaluated diﬀerent measures of adherence, both individually and in combination. The questionnaire assessing drug intake during the previous four days (two items) and the previous week-end (one item) showed a high level of adherence, as reported elsewhere [21, 33]. Nevertheless, the association with virological failure was weak and was only signiﬁcant in previously ARV-na¨ıve patients. Moreover, this association disappeared in multivariate analysis. These results may be explained partly by issues of social desirability and the loss of anonymity when the patient needed help from a nurse to answer the questionnaire [25]. We also evaluated MCV and plasma drug assay, as more objective measurements of adherence [25, 26]. We found that 93% of patients had drug concentrations within the target range, suggesting a high level of adherence. The favorable pharmacokinetic properties of NNRTIs, which have long half-lives and good oral absorption, ensure consistent drug concentrations and could thus explain this result. Never- theless, even if the association between virological success and optimal therapeutic drug concentrations was strong in univariate and multivariate analysis, drug assays are diﬃcult to implement in Cambodia, especially in the province where most of patients lived. Furthermore, although drug assay is readily available in low- to middle-income countries, it is unlikely that it would be cost-eﬀective for monitoring HAART.