Pellagra is caused by cellular deficiency of niacin or its precursor amino acid, tryptophan. Isoniazid preventive therapy (IPT) is the administration of isoniazid (INH) to latent tuberculosis (TB) infection affected people preventing advancement to active TB disease. Although potentially life-saving for human immunodeficiency virus (HIV)-infected people with no active TB, IPT is arguably a possible player in pellagra in addition to well-known malnourishment determinants particularly in developing nations where diagnosis is often overlooked or delayed. A case study examines clinical presentation and possible causes of pellagra, in HIV + patient on isoniazid prophylaxis. The 30 year old female on routine antiretroviral therapy presented with diarrhea, abdominal discomfort, painful swallowing, and epigastric pain, facial rash spread on the forehead, nose, cheeks and the chin, upper and lower limbs. Withdrawal of isoniazid, administration of nicotinamide and niacin supplements showed clinical improvement in four weeks. Decreased serum tryptophan in persons living with HIV (PLHIV) under IPT and lack of minimum dietary proteins threshold would be pointers to isoniazid induced pellagra risk. Appropriate dietary intake and counseling ought to be emphasized among PLHIV. Tryptophan and nicotinamide serum levels should be part of baseline investigations in PLHIV starting IPT and where feasible clinically, niacin/nicotinamide supplementation be adopted.