Pain and sensory function in HIV-infection : with and without antiretroviral therapy

Abstract

Pain is a common symptom throughout the course of HIV-1 infection, with a prevalence ranging between 30-80%, varying with study methodology and patient selection. Neurogenic pain may appear as a consequence of distal predominantly sensory neuropathy (DSP), a common HIV-1 related neurological complication of late HIV-1 infection, usually during the AIDS-stage of the disease. This study set out to analyse pain and sensory function in HIV-1 infected patients with and without highly active antiretroviral therapy (HAART).

In study I, a questionnaire was used to assess prevalence of pain and sensory symptoms in 211 consecutive HIV-1 infected patients without HAART attending the HIV clinic at Huddinge University Hospital. The mortality rate was assessed 15 months after completion of the questionnaire. Data on antiretroviral treatment, mode of HIV-1 transmission and immunological status were gathered retrospectively from the case files. Pain was found to be highly prevalent, ranging between 59 and 100%. Pain was more prevalent among patients with intravenous drug use (IDU) than among non-IDUs. The presence of pain correlated positively to both immunological status and mortality, but only in non-IDU patients, as did sensory symptoms other than pain in both groups. Forty-four % of the patients diagnosed with AIDS reported symmetrical sensory symptoms in the lower extremities, out of which half complained of extremity pain.

In study II, sensory function was analysed in HIV-1 infected patients with painful and nonpainful DSP, without HAART, by clinical examination, quantitative thermal testing (QTT) and nerve conduction studies. Patients with painful neuropathy had a pronounced impairment of innocuous warm perception, which in the setting of impaired or absent heat pain perception, suggests a more generalised loss of function in somatosensory C-fibre channels, compared to patients with non-painful neuropathy.

In study III, the development of fine calibre nerve channel neurotoxicity related to antiretroviral agents (didanosine, zalcitabine and stavudine), commonly included in HAART, was monitored. Interestingly, we found that virologically successful HAART (also including neurotoxic drugs) had the capacity to restore function in fine calibre somatosensory nerve channels, especially in patients with less advanced immunodeficiency before start of therapy, the latter indicating a shorter duration of the neurological deficit.

QTT assess function of fine calibre nerve channels from the receptor to the cerebral cortex. Recent studies suggest that HAART also may improve HIV-1 related complications of the central nervous system (CNS). Therefore, it is not unlikely that the observed improvement of thermal and nociceptive somatosensory functions to some extent could be related to improved function of central pathways, which may be reflected by the degree of inflammation and viral load of the CSF.

In study IV and V, we analysed viral load and inflammatory changes of the CNS by cerebrospinal fluid (CSF) in HIV-1 infected patients with and without indinavir-based HAART. In study IV, approximately 50% of HIV-1 infected patients without HAART had CSF leucopenia and the number of mononuclear cells (MNC) in CSF correlated strongly with the blood CD4+ cell count. HIV-1 nucleic acid (RNA) could be detected in the majority of patients, and a strong correlation was found between the number of CSF MNC and the CSF HIV-1 RNA levels, suggesting that most of the virus detected in the CSF emanated from circulating MNC of systemic origin, not from the brain.

In HIV-1 infected patients of study V, treated with indinavir-based HAART, only one fifth had detectable CSF HIV-1 RNA at threshold levels, and inflammatory CSF parameters had normalised (cell content and IgG-index). The protease inhibitor indinavir could be detected in the CSF in therapeutic concentrations in all patients, and thus probably contributing to the observed antiretroviral effect.