Article

Substance abuse increases the risk of neuropathy in an HIV-infected cohort

Department of Neurology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1052, New York, New York 10029, USA.
Muscle & Nerve (Impact Factor: 2.31). 04/2012; 45(4):471-6. DOI: 10.1002/mus.23231
Source: PubMed

ABSTRACT Human immunodeficiency virus (HIV)-infected patients commonly develop distal symmetric polyneuropathy (DSP). Age, ethnicity, and toxic exposures may influence the risk. In this study we examined the association between substance use, antiretrovirals, ethnicity, and incident neuropathy in an HIV-infected cohort.
Data were obtained from the National NeuroAIDS Tissue Consortium (NNTC), an ongoing, prospective cohort started in 1998. Cox proportional hazards models were used to examine the association of substance use, demographics, neurotoxic antiretrovirals, and laboratory parameters with incident neuropathy in 636 participants who were neuropathy-free at baseline.
The cumulative incidence of DSP was 41%. Substance use (P = 0.04), number of substances used (P = 0.04), and longer duration of HIV infection (P = 0.05) were associated with incident DSP, but demographic factors, use of neurotoxic antiretrovirals, and laboratory parameters were not.
Substance use and longer duration of HIV infection are risk factors for DSP in HIV-infected patients. Use of multiple substances may be particularly risky.

1 Follower
 · 
194 Views
  • Source
    01/2015; 20. DOI:10.11604/pamj.2015.20.392.5799
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The introduction of antiretroviral therapy (ART) has dramatically reduced the mortality rate of people living with HIV (PLHIV). However, complications of both HIV and ART, such as peripheral neuropathy currently affect PLHIV. The purpose of this study was to establish the prevalence of peripheral neuropathy of the lower extremity and, its association with demographic and health status, characteristics among people on ART in Rwanda. A cross sectional study was conducted among 507 women and men aged between 18 and 60 years, on ART, randomly selected from eight selected ART clinics in Rwanda. Brief Peripheral Neuropathy Screen was used to assess peripheral neuropathy. Peripheral neuropathy prevalence was 59% overall, mean age of the participants was 39.7 (+/-9.2) and a slightly older age was associated with peripheral neuropathy; [42(+/-9.2) vs 37 (+/-8.8) (p < 0.001)]. 78% of participants living in urban settings compared to 40% in rural settings reported peripheral neuropathy, 69% of participants with higher levels of education (secondary level and above) reported lower extremity neuropathy.The three factors were significantly associated with peripheral neuropathy in multivariable model analysis: older age [aOR = 1.1, 95% CI (1.0, 1.2), p < 0.001], primary education level [aOR = 0.6 95% Cl (0.3, 1.0), p = 0.04] and urban setting [aOR = 0.1, 95% CI (0.06, 0.3), p < 0.001], after adjusting for other factors. None of the health status characteristics namely; the level of CD4 cell count, duration of HIV infection and duration on ART, was independently associated with peripheral neuropathy. The prevalence of peripheral neuropathy among PLHIV on ART in Rwanda is high. It is unclear why urban setting has an effect on PN levels in this cross sectional study, but does suggest that unidentified social and lifestyles factors may have a role in subjective symptoms and objective signs, of PN.
    BMC Public Health 12/2014; 14(1):1306. DOI:10.1186/1471-2458-14-1306 · 2.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infection of the CNS with HIV-1 occurs rapidly after primary peripheral infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders. Our previous work has shown that the selected neurotoxic effects induced by individual viral proteins, Tat and gp120, and by HIV+ supernatant are enhanced by co-exposure to morphine. This mimics co-morbid neurological effects observed in opiate-abusing HIV+ patients. Although there is a correlation between opiate drug abuse and progression of HIV-1-associated neurocognitive disorders, the mechanisms underlying interactions between HIV-1 and opiates remain obscure. Previous studies have shown that HIV-1 induces neurotoxic effects through abnormal activation of GSK3β. Interestingly, expression of GSK3β has shown to be elevated in brains of young opiate abusers indicating that GSK3β is also linked to neuropathology seen with opiate abusing patients. Thus, we hypothesize that GSK3β activation is a point of convergence for HIV- and opiate-mediated interactive neurotoxic effects. Neuronal cultures were treated with supernatant from HIV-1SF162-infected THP-1 cells, in the presence or absence of morphine and GSK3β inhibitors. Our results show that GSK3β inhibitors, including valproate and small molecule inhibitors, significantly reduce HIV-1-mediated neurotoxic outcomes, and also negate interactions with morphine that result in cell death, suggesting that GSK3β-activation is an important point of convergence and a potential therapeutic target for HIV- and opiate-mediated neurocognitive deficits.
    Molecular and Cellular Neuroscience 01/2015; 65. DOI:10.1016/j.mcn.2015.01.001 · 3.73 Impact Factor

Full-text (2 Sources)

Download
67 Downloads
Available from
May 23, 2014