- Objective A significant number of HIV-1 patients experience poor immune reconstitution despite long-term viral suppression with highly active antiretroviral therapy (immunological non-responders). The aims of the present study were to determine whether eradication of Helicobacter pylori could facilitate a better immune reconstitution in these patients. Methods Forty-nine immunological non-responder HIV-1 patients were evaluated by 13C-urea breath test (UBT) for the presence of active H. pylori infection. They were all asymptomatic. The UBT was positive in 26 (53%) of them. Eleven patients (group 1) were treated with a combination of omeprazole 20 mg bid, amoxicillin 1 g bid and clarithromycin 500 mg bid for 14 consecutive days. Eight weeks later, successful eradication was proven by a repeat negative UBT in all 11 patients. The remaining 15 (group 2) refused the H. pylori eradication treatment. All 26 patients were followed for 24 months and evaluated for blood CD4 and CD8 cell counts and percentages and for plasma HIV-1 viral load. Results At the time of H. pylori diagnosis and eradication (baseline), CD4 and CD8 cell counts were similar in both study groups. All 11 H. pylori eradicated patients (group 1) had a significant increase in CD4 cell count starting 3 months and peaking 12–18 months after H. pylori eradication. Thereafter, CD4 levels gradually declined. Nevertheless, 24 months after triple therapy it was significantly higher than prior to H. pylori eradication. Parallel reciprocal changes were observed in CD8 cell counts. There were no significant changes in either CD4 or CD8 cell counts in group 2 patients. None of the patients of group 1 demonstrated virological failure, while four (26.7%) group 2 patients experienced virological failure requiring change of highly active antiretroviral therapy (HAART) regimen. Conclusion Triple therapy for H. pylori eradication is associated with a significant, although possibly transient immune reconstitution in HAART-treated HIV-1 patients with viral suppression without immunological response.