Motor neuron disease (MND) have an incidence of 2 in 100 000 persons, resulting in the death of 1 in every 500 people affected. The most common disease in MND spectrum is amyotrophic lateral sclerosis (ALS). We describe the case of an ALS-like syndrome in a HIV patient. This case report presents a 38 years old male from Peru with HIV who after 2 months of combined antiretroviral treatment (cART) initiation was admitted to the hospital for spastic paraplegia. On his first admission, rapid plasma reagent (RPR) was positive and he was treated for neurosyphilis and discharged. Nevertheless, one month after, he was admitted for the second time because paraplegia persisted. Laboratory tests, electromyography and imaging were performed, and ALS was diagnosed. Normally, HIV treated patient with ALS tend to have a better prognosis, however this was not the case. In this case report, we discuss possible association between ALS and immune reconstitution inflammatory syndrome in HIV patients.