Abstract Body

Background:

Antiretroviral therapy (ART) leads to a reduction in AIDS-related events and lower CD4 counts are associated with some non-AIDS events. The impact of long term virological suppression on non-AIDS related cancers (NADC) is unclear. We determined whether the most recent CD4 count was an independent predictor of incident cancer risk in people with HIV who had virologic suppression (VS) for at least 2 years.

Methods:

Individuals from the D:A:D and RESPOND cohort collaborations who achieved 2 years of VS on ART were included. Follow-up was from baseline (date of VS for 2 years) until the earliest of a first cancer event, confirmed virological failure (>200 copies/mL) or cessation of ART for >2 months, final follow-up, or administrative censoring date (D:A:D: 2/1/2016; RESPOND: 12/31/2021). Multivariable Poisson regression was used to assess associations between cancer incidence (total, AIDS-defining cancer (ADC), NADC, infection-related, smoking-related and BMI-related cancer) and time updated CD4 count (<350, 350-499, 500-749 and >750 cells/µL) stratified by pre-ART nadir CD4 count and adjusted for confounders determined a priori.

Results:

Overall, 51,622 people with VS were included (median [IQR] baseline age 44 years [37, 51], CD4 count 536 cells/µL [376, 729], nadir CD4 count 238 cells/µL [112, 386], 72% male, 36% current smokers). There were 2152 incident cancers during a total of 321,126 person-years of follow-up (PYFU), median 6 years [2.9, 9.5]) (incidence rate (IR)/1000 PYFU 6.70 [95% confidence interval 6.42, 6.99]). This included 276 ADC (0.86 [0.76, 0.97]/1000 PYFU), and 1876 NADC (5.84 [5.58, 6.11]). There were 721 infection-related (2.24 [2.08, 2.41]), 927 smoking-related (2.89 [2.7, 3.08]), and 491 BMI-related (1.53 [1.4, 1.67]) cancers, which were not mutually exclusive. After adjustment, there was a significant reduction in the adjusted IR ratio (aIRR) by higher time-updated CD4 count for all cancers (overall and by type) stratified by nadir CD4 count (Figure). No significant interaction between time-updated CD4 count and time-updated age, or calendar periods was present.

Conclusions:

Despite being virologically supressed on ART for >2 years, individuals with poorer immune recovery (CD4 <500 cells/µL) continue to experience a significantly higher incidence of all cancer groups. This underscores the importance of earliest possible diagnosis of HIV and prompt initiation of ART to ensure optimal sustained risk reduction of both ADC and NADC.