Reekie, JM; (2012) The long term durability of combination antiretroviral therapy in HIV-positive patients across Europe. Doctoral thesis , UCL (University College London).

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Abstract

Despite dramatic improvements in the quantity and quality of life for Human Immunodeficiency Virus (HIV) positive people with the introduction of combination antiretroviral therapy (cART), all-cause mortality rates remain higher than the general population. Furthermore, treatment is a lifelong commitment and a substantial burden on patient life. The aim of this thesis was therefore to assess the long term durability of cART through assessing various clinical, virological and immunological outcomes including mortality in HIV-positive patients across Europe. The analyses were based on data from the EuroSIDA cohort, an observational cohort of more than 16000 HIV-positive patients from Europe, Israel and Argentina. Results showed that HIV-positive patients on a well-tolerated and fully suppressive cART regimen have a small risk of treatment failure occurring over the next 6 months and could therefore be monitored less frequently. In contrast patients who have spent a low percentage of time with a suppressed viral load whilst on cART or who have recently rebounded may require more intensive monitoring after making a treatment switch. In patients who have achieved an initial response and tolerated the first three months of treatment, nevirapine efavirenz and lopinavir based cART regimens all have similar durability based on risk of all-cause discontinuation and development of serious clinical events. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS related malignancies. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes in part due to differences in use of effective cART. In conclusion results from this thesis provide evidence that could help improve the long term durability of cART for HIV-positive patients through different measures of healthcare capturing the wide aspects of treatment and outcomes.

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