| Summary: | It has been long established that adherence to highly active antiretroviral therapy (HAART) is extremely important for therapeutic outcomes for the treatment of HIV-infection. With the advent of HAART, decreases in morbidity and mortality have been observed in HIVinfected individuals. However, these decreases have not generally been extended to injection drug users (IDUs) whom have additional barrier to access HAART, including adherence. Strategies such as directly observed therapy (DOT) have been successful in treating IDUs, especially when they are used in conjunction with methadone maintenance programs. Within these programs HAART and methadone are co-administered, which makes it possible to estimate HAART adherence through a surrogate, methadone adherence. With this in mind we sought to assess if ongoing illicit drug use within such a program would affect methadone adherence. Decreased methadone adherence was noted during periods of opiate use. Furthermore, we sought to assess the relationships between HAART adherence and each of virologic suppression and the emergence of drug resistance mutations. In the former, robust rates of virologic suppression were observed at every adherence level during maintenance therapy with the exception of the 80-90% adherence level where higher rates of virologic failure were observed. This may be explained by a phenomena observed when assessing the latter where higher rates of the accumulation of new drug resistance mutations were observed at the 80-90% level. Although this intermediate level of adherence has been previously described, the estimated range of adherence values reported in this thesis is much narrower than those reported in the literature. All such analyses were conducted in a longitudinal framework, with data analysis done using generalized estimating equations (GEE). Although a cross-sectional approach is typically conducted for these types of studies, a longitudinal approach is better able to localize the outcomes (e.g. virologic suppression) to the periods and patterns of non-adherence. This may explain some of the differences found in the studies contained in this thesis which may disagree with the findings in previous reports. With this in mind, it may be important to look at adherence to HAART in a more insightful manner than has been traditionally done. === Science, Faculty of === Statistics, Department of === Graduate
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