Background Since antiretroviral therapy (ART), HIV-infected individuals experience mainly non-AIDS-related conditions, among which infectious events are prominent. We aimed to estimate incidence and describe overall spectrum of infectious events, including all grade events, among HIV-1-infected adults failing first-line ART in Yaoundé, Cameroon. Methods All patients from Cameroon enrolled in the second-line ART 2LADY trial (ANRS12169) were included in this secondary analysis. Medical files were reviewed with predefined criteria for diagnosis assessment. Incidence rates (IR) were estimated per 100 person-years (% PY). Results A total of 302 adult patients contributing 840 PY experienced 596 infectious events (IR 71% PY). Only 29 (5%) events were graded as severe. Most frequent infections were upper respiratory tract infections (15% PY), diarrhoea (9% PY) and malaria (9% PY). A total of 369 (62%) infections occurred during the first year (IR 130% PY) followed by a persistent lower incidence during the following 3 years. Higher IR were observed in patients with CD4⁺ T-cell count ≤200 cells/mm³ for all infectious events except for mycobacterial and parasitic infections. IR of viral, bacterial and parasitic infectious events were lower in case of co-trimoxazole use in patients with CD4⁺ T-cell count ≤200 cells/mm³. Conclusions Infectious events are common and mainly occur during the first year after treatment initiation. Second-line ART initiation had a positive impact on the entire spectrum of infectious morbidity.