Springer Science and Business Media LLC

The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy.

We identified subjects who had CSF HIV RNA concentrations below 50 copies/mL at the time combination antiretroviral therapy was interrupted, and for whom CSF samples were available before and after the interruption.

A total of 8 subjects were studied. The median (range) CSF NFL level at baseline was <125 (<125–220) ng/L (normal <250 ng/L). All 8 subjects exhibited an increase in CSF and plasma HIV RNA after stopping therapy, accompanied by intrathecal immunoactivation as evidenced by CSF lymphocytic pleocytosis (7/8 patients) and increased CSF neopterin concentration (5/6 patients). Three subjects showed a consistent increase in CSF NFL, rising from <125 ng/L to a maximum of 880 (at day 148), 1,010 (day 58) and 10,930 ng/L (day 101). None exhibited new neurological symptoms or signs, or experienced functional deterioration during the period off treatment; of 5 who underwent brief quantitative neurological testing, none showed worsening performance.

These findings suggest that resurgence of active HIV replication may result in measurable, albeit subclinical, CNS injury. Further studies are needed to define the frequency and pathobiological importance of the increase in CSF NFL.

The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients.

A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand.

From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm³ (IQR 22, 127). GPO-VIR^® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm³) and the increment of CD4 cell count of < 50 cell/mm³ after 6 months of cART were the predictors for immunological failure (p < 0.001).

This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART.