We report an individual with rapidly progressive motor neuron disease (MND), phenotypically compatible with amyotrophic lateral sclerosis (ALS). The patient described in this case report proved positive for human immunodeficiency virus (HIV) and was initiated on antiretroviral therapy (ART). Following ART he clinically stabilised over 10 years and deteriorated again due to noncompliance or ART resistance. HIV infection can give rise to an MND mimic, HIV-ALS. The improvement in response to ART supports the notion that HIV-ALS is a treatable entity also in Africa. This is the first case report of a patient with HIV-ALS and long term follow up in Sub-Saharan Africa. The report raises the suggestion that an additional (retro)virus can play a role in the aetiology of ALS.