2515. Clinical Relevance of Immune Non-Response Among Virally Suppressed Adults Living with HIV in Africa and the United States

BACKGROUND: Immune non-response (INR) for people living with HIV (PLWH) is the inability to regain healthy CD4 counts despite viral suppression (VS) on antiretroviral therapy (ART). We identified factors associated with INR in two methodologically similar but demographically diverse cohorts with open access to care and assessed the relationship between INR and incident serious non-AIDS event (SNAE). METHODS: The US Military HIV Natural History Study (NHS) and the African Cohort Study (AFRICOS) are multisite, open cohort studies enrolling PLWH. Participants with 2 years of VS < 400 copies/mL on ART were evaluated for INR, defined as CD4 < 350 cells/µL at 2 years VS. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHR) and 95% CIs for factors associated with incident SNAE (first non-AIDS cancer, cardiovascular, gastrointestinal, genitourinary, liver, musculoskeletal or respiratory event) after 2 years of VS. RESULTS: 10.8% of the 1,784 NHS and 25.8% of the 984 AFRICOS subjects had INR. The AFRICOS cohort was older and had a higher proportion of females. In both cohorts, immune non-responders were significantly older and had a significantly lower CD4 at ART initiation. Those with INR also took longer to reach 2 years of VS since starting ART. Odds of INR decreased by over 60% for every 100 cell increase in baseline CD4 in both cohorts (NHS aOR = 0.31 [95% CI 0.26, 0.37]; AFRICOS aOR = 0.36 [95% CI 0.21, 0.86]). In the NHS, hazard of incident SNAE was 61% higher for those with INR (aHR = 1.61 [95% CI 1.12, 2.33]). Probability of SNAE-free survival at 15 years since 2 years of VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. CONCLUSION: INR was common in two diverse cohorts with open access to care and treatment. The association with SNAEs suggests early identification of and interventions to prevent or reverse INR may improve clinical outcomes, but further study is needed. The clinical relevance of INR highlights the value of early HIV identification and treatment, and suggests CD4 monitoring at ART initiation and post-VS is important in settings where INR is prevalent. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.