Background:  Toxic effects of HAART emerge in all organs and are well known in the peripheral nerve system.

Methods:  The neurotoxic effect of the antiretroviral drugs didanosine (ddI), dideoxycytidine (ddC), stavudine (d4T) as part of HAART on neurocognitive function during HIV infection was studied. In a retrospective cross-sectional study the parameters of event-related potentials were analyzed from patients receiving HAART with ddI, ddC, and d4T for at least 3 month (n = 60) with a mean intake of 19±6 months (mv±1 SD). Results were compared to a control group receiving HAART without these substances. The latency of P2, N2, P3, and the amplitude of P3 of event-related potentials and the mean reaction time were analyzed. Besides event-related potentials examinations on cognitive impairment and distal-symmetric polyneuropathy (DSP) were performed using routine clinical and neurophysiological methods.

Results:  Statistical analysis revealed no significant difference for age, sex, CDC-stages, CD4⁺ cell count, and plasma viral load between both collectives. Patients treated with ddI, ddC, and d4T showed a significant latency prolongation of the P3 component of 448±45 vs 431±33 msec (mv±1 SD) (p <0.02 ). Routine clinical and neurophysiological methods revealed significant higher prevalence of cognitive impairment and DSP in the group receiving HAART with ddI, ddC, or d4T (p <0.009).

Conclusions:  In concordance to earlier publications, these results show, using clinical and neurophysiological methods, that ddI, ddC, and d4T cause cognitive impairment in the central nervous system. It is assumed that these alterations are induced by the toxic impact of ddI, ddC, and d4T on γ-polymerase in mitochondria’s of the central nervous system (CNS). As shown in newborns, this toxic effect may last as long as 2 years after finishing HAART. It is assumed that neurotoxic effects of ddI, ddC, and d4T may also take part in the development of newer forms of HIV-associated neurocognitive disorders.