Schultze, Anna Theresia; (2017) The Epidemiology and Consequences of HIV Drug Resistance : Analyses of resistance data from European cohort studies. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Although the roll-out of effective combination antiretroviral therapy (cART) has brought great benefits, concerns remain regarding the development of drug resistance. This thesis uses data from the EuroSIDA cohort, the UK Collaborative HIV cohort, the UK HIV Drug Resistance Database, the ViroLAB consortium and the EU-Resist collaboration to describe trends in resistance testing, prevalence and incidence as well as the impact of drug resistance on CD4 count declines both in the presence and absence of ART. My findings show that the proportion of people tested for resistance following virological failure in Europe is low (31.6%) and decreasing. Individuals in Eastern Europe were less likely to receive a resistance test (adjusted odds ratio=0.72, 95% confidence interval=0.55-0.94) compared with individuals in Southern Europe. However, among those who were tested, the proportion with resistance was relatively high (77.9%), indicating a potentially selective approach to resistance testing. Among individuals maintained on a failing treatment regimen with resistance to at least one drug class, I found that CD4 counts declined less steeply among individuals with NRTI resistance, the M184V, D67N or T215Y mutation in the reverse transcriptase, or either the V82A or I54V mutation in the protease. In contrast, CD4 counts declined faster among individuals with NNRTI resistance and those with the V179D or L74I reverse transcriptase mutations. A cluster of mutations, including K103N, was also associated with faster CD4 declines. No class of drug resistance or individual mutation had a large impact on the rate of CD4 decline before the start of cART. These findings have implications for public health policy in Europe aimed at minimizing health disparities, and can be used to provide recommendations for the construction of maintenance therapies for individuals with no other treatment options. Further research into HIV drug resistance is imperative to ensure the continued success of cART.

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