Currently, there is a global increase in Helicobacter pylori (H. pylori) antimicrobial resistance with an increase in parallel of H. pylori treatment failure in the general population in several regions. At the same time and in relation to the pandemic of HIV infection, little is presently known on H. pylori-HIV co-infected people who receive H. pylori treatment based on international guidelines for the general population. We believe that this HIV co-infected population is a special niche because it harbors strains with multiple resistances to antibiotics compared to the general population; hence this co-infected population should receive specific recommendations in relation to their condition. Therefore, based on current literature, we propose a “best approach” to offer optimal efficacy of H. pylori treatments in people living with H. pylori and HIV co-infection.