UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Studies on clinical and epidemiological factors associated with peripheral neuropathy and severe hyperlactatemia or lactic acidosis in HIV-infected adults exposed to nucleoside analogues reverse transcriptase inhibitors.

Rafael Arenas-Pinto, A.; (2007) Studies on clinical and epidemiological factors associated with peripheral neuropathy and severe hyperlactatemia or lactic acidosis in HIV-infected adults exposed to nucleoside analogues reverse transcriptase inhibitors. Doctoral thesis , University of London. Green open access

[thumbnail of U591285.pdf] PDF
U591285.pdf

Download (8MB)

Abstract

Studies on mitochondrial dysfunction in HIV-infected adults exposed to anti-retroviral therapy. A significant proportion of HIV-infected patients who require anti-retroviral therapy are or have been exposed to nucleoside analogue reverse transcriptase inhibitors (NRTIs). It has been consistently suggested that most of the NRTI-attributed adverse drug reactions (ADR) are due to mitochondrial dysfunction. In a sub-analysis of a large randomised clinical trial (Delta) the incidence of peripheral neuropathy (PN) was constant over time in all study arms, which does not support the hypothesis of cumulative toxicity previously proposed for NRTI-induced ADR. Patients taking zidovudine (AZT)/zalcitabine (ddC) combination were more likely to develop PN than patients on AZT monotherapy (RH= 2.30 95%CI= 1.62 - 3.28). The incidence of PN among patients exposed to zidovudine/didanosine (AZT/ddl) combination was not different from that observed in patients on AZT. In a multi-centre case-control study including 110 cases of lactic acidosis (LA) or severe hyperlactataemia (HL) patients with < 200 CD4 cell/pl were more likely to develop HL/LA than patients with higher levels of CD4 cells (OR=3.44 95%CI= 1.64 - 7.22). Female patients were found to be at higher risk for HULA than men (OR= 4.75 95%CI= 1.96 - 11.53). Patients exposed to either d4T, ddl or the combination of these two were four to six times more likely to develop HL/LA than patients taking other NRTIs based combinations. Interestingly, cases of HL/LA were exposed to d4T for shorter periods of time than controls. Almost 10 % of the cases included in the study were asymptomatic at the time of diagnosis. All these symptom-free cases had blood lactate ranging between 5 and 7 mmol/l. Therefore, case definitions for HL or LA based on clinical presentation may underestimate the magnitude of the problem.

Type: Thesis (Doctoral)
Title: Studies on clinical and epidemiological factors associated with peripheral neuropathy and severe hyperlactatemia or lactic acidosis in HIV-infected adults exposed to nucleoside analogues reverse transcriptase inhibitors.
Identifier: PQ ETD:591285
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material and sensitive information have been removed from the ethesis
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/1444011
Downloads since deposit
145Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item