UBC Theses and Dissertations
Treatment of HIV infection in injection drug users Tossonian, Haroutioun Krikor
The treatment of HIV infection in injection drug users (IDUs) is limited by multiple barriers which could be addressed by using strategies based on directly observed therapy (DOT) or similar programs. This thesis evaluates a systematic approach of treatment within the context of an established methadone-based DOT program. First, we compared treatment responses with DOT relative to self-administered therapy (SAT) within a longitudinal cohort study. Higher rates of virologic suppression and retention on highly active antiretroviral therapy (HAART) were achieved with regimens taken as DOT over a period of 2 years. We also compared rates of emergence of drug resistance mutations (DRMs) with DOT relative to SAT. Although DOT did not prevent the emergence of DRMs, it did not lead to higher levels of resistance. We estimated the prevalence of primary drug resistance in our antiretroviral naive IDU cohort and found it to be relatively low (4.7%) but polymorphisms in the reverse transcriptase (RT) and protease genes were very common. Mutations at RT codon 135 (frequent in our cohort) were found to have no impact on treatment responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. However, in patients experiencing virologic breakthrough and harboring such mutations, there was more evolution of single and less evolution of multiple NNRTI mutations. We measured the incidence of hepatotoxicity in IDUs receiving nevirapine-based HAART and compared it to that measured in non-IDUs. Hepatotoxicity was observed in 15% of participants in both IDUs and non-IDUs during the first year of therapy. Hepatitis C virus co-infection, being naive to HAART and abnormal baseline alanine aminotransferase levels were associated with higher risk of hepatotoxicity. Finally, we evaluated methadone dose adjustments and treatment responses after initiating HAART. Our results demonstrated that with nevirapine and efavirenz, moderate increases in methadone dosage were required to maintain the therapeutic benefit of opiate substitution therapy, compared to no change required in patients receiving regimens containing lopinavir or atazanavir. Taken together, our data demonstrate that programmatic interventions including DOT are effective in managing HIV-infected IDUs with few if any drawbacks in terms of drug resistance, drug toxicity or interactions with other therapeutic interventions.
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