CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Multiple factors have been associated with HAND during HIV-1 B and non-B subtype infections, and infecting subtypes have been implicated in bot the incidence and severity of HAND. This study of ethnically and culturally similar individuals demonstrated that factors that have long been associated with HAND (i.e. CD4 nadir, AIDS, viral diversity) are more likely to be associated with HAND than differences in infecting subtypes B, C or B/C. 457 Peripheral Neuropathy at First-Line Failure and on Second Line in Sub-Saharan Africa Alejandro Arenas-Pinto 1 ; JenniferThompson 1 ; Godfrey Musoro 4 ; Helen Mussana 5 ; Abbas Lugemwa 3 ; Andrew D. Kambugu 2 ; Aggrey Mweemba 6 ; SarahWalker 1 ; Paton Nicholas 1 On behalf of the EARNESTTrialTeam 1 University College London, London, United Kingdom; 2 Makerere University, Kampala, Uganda; 3 Joint Clinical Research Centre, Mbarara, Uganda; 4 University of Zimbabwe, Harare, Zimbabwe; 5 Joint Clinical Research Centre, Kampala, Uganda; 6 University Teaching Hospital, Lusaka, Zambia Background: Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective anti-retroviral therapy (ART). Data on PN during second-line cART is scarce. Methods: We assessed PN using the ACTG Brief Peripheral Neuropathy Screen tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in the EARNEST trial. Patients were randomised to a PI (standardised to lopinavir/ritonavir) plus either 2/3 NRTIs (80% TDF-based) or raltegravir, or as PI monotherapy (after 12 week induction with raltegravir). Factors associated with PN were investigated using logistic regression. Results: Symptomatic PN (SPN) prevalence was 22% at switch to second-line (N=1251) and was independently associated (p<0.05) with older age (OR=1.04 per year), female gender (OR=1.64), history of TB (OR=1.86), smoking (OR=1.61), higher plasma creatinine (OR=1.09 per 0.1mg/dl increase), lower CD4 cell count (OR=0.83 per doubling) and not consuming alcohol (OR=0.54). Overall, SPN prevalence decreased to 17% by week 96 (p=0.0002) following similar trends in all treatment groups (p=0.30). Asymptomatic PN (APN) increased over the same period from 21% to 29% (p<0.0001) and prevalence of signs suggestive of PN regardless of symptoms remained stable (44% and 46% at entry and week 96 respectively). At week 48 and 96, after adjusting for time updated associations above and CD4 count and viral load at switch, SPN was not associated with current CD4 count (p=0.10) or VL (p=0.97) but was strongly associated with TB (p<0.0001). Including exposure to isoniazid had a comparable effect to that of TB. By week 96, new SPN incidence was 10%, and SPN had resolved in 58% reporting SPN at switch. Isoniazid-based TB treatment was prescribed during study period to 18% of patients who developed incident SPN, but only to 6% of those patients who never developed SPN (P<0.001).

Figure: Percentage of Patients with SPN Conclusions: SPN prevalence was significantly reduced with PI-based second-line therapy in all treatment groups, but we did not find any advantage to the NRTI-free regimens tested in EARNEST. The increase of APN and stability of PN-signs regardless of symptoms over 96 weeks suggest that there may be an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. In addition to other known risk factors such as age, female gender and low CD4 count, SPN was strongly associated with exposure to isoniazid to treat TB. 458 Prevalence of and Risk Factors for Peripheral Neuropathy in Rakai, Uganda Deanna R. Saylor 1 ; Gertrude Nakigozi 2 ; Noeline Nakasujja 3 ; Xiangrong Kong 4 ; Kevin Robertson 5 ; Ronald H. Gray 4 ; Maria J.Wawer 4 ; Ned Sacktor 1 1 Johns Hopkins School of Medicine, Baltimore, MD, US; 2 Rakai Health Sciences Program, Entebbe, Uganda; 3 Makerere University College of Health Sciences, Kampala, Uganda; 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 5 University of North Carolina, Chapel Hill, NC, US Background: Peripheral neuropathy (PN) is a common and potentially debilitating neurologic complication of HIV infection. Systematic studies to identify the prevalence of and risk factors for PN in sub-Saharan Africa are lacking. Methods: A sample of participants in the Rakai Community Cohort Study underwent detailed neurological evaluation including assessment of demographic characteristics, subjective PN symptoms, and a neurological examination by a trained medical officer. PN was defined as > 1 sign on examination (e.g. decreased pinprick or vibration in the fingers or toes, distal weakness, or reduced/ absent ankle reflexes) and > 1 subjective symptom (e.g. paresthesias, numbness, or pain in the hands or feet). PN risk factors were determined by comparing characteristics of participants with and without neuropathy using t-tests for continuous variables and chi-squared tests for categorical variables. Results: 538 participants were enrolled: 200 HIV-positive (HIV+) antiretroviral (ARV) naïve participants with moderate immunosuppression (CD4 count 351-500), 107 HIV+ ARV-naïve participants with advanced immunosuppression (CD4 count <200), and 231 age and gender-matched HIV-negative (HIV-) participants. There were no demographic differences between HIV+ and HIV- participants, but HIV+ participants with advanced immunosuppression were younger (34 years vs. 37 years, p=0.002), more likely to be male (62% vs. 45%, p=0.004), and had lower body mass indexes (BMI) (20.7 vs. 23.0, p<0.001) than those with moderate immunosuppression. PN was more prevalent among HIV+ than HIV- participants (24% vs. 8%, p<0.001) and showed a trend toward statistical significance among HIV+ participants with advanced immunosuppression versus those with moderate immunosuppression (30% vs. 20%, p=0.05). In addition to HIV status and level of immunosuppression, older age (mean: 38 years vs. 35 years, p=0.03) was also a significant predictor of PN, but BMI (p=0.45), alcohol use (p=0.78), and prior isoniazid use (p=0.06) were not. PN severity was worse in HIV+ than HIV- participants as assessed by the Modified Total Neuropathy Scale (p=0.003). Conclusions: PN is prevalent in rural Uganda and is more common in HIV+ individuals, with a trend toward increased prevalence in those with advanced disease. PN prevalence also increases with age. This highlights the need for early diagnosis and treatment of HIV to prevent this potentially debilitating complication and the necessity of close monitoring for PN as the HIV+ population ages.

Poster Abstracts

315

CROI 2015