Clinical effects of durability of immunosuppression in virologically suppressed ART-initiating persons with HIV in Latin America. A retrospective cohort study

Background Clinical outcomes are rarely studied in virologically suppressed people living with HIV (PWH) and incomplete CD4 recovery. To explore whether time living with severe immunosuppression predict clinical outcomes better than baseline or time updated CD4, we estimated the association between cumulative percentage of time with CD4 < 200 cells/mu L during viral suppression (VS) (%t(CD4<200)), and mortality and comorbidities during 2000-2019. Methods In a retrospective cohort analysis, we followed PWH initiating ART in Latin America from first VS (HIV-RNA<200 copies/mu L) to death, virological failure or loss to follow-up. We fit Cox models to estimate risk of death and/or AIDS-defining and serious non-AIDS-defining events (ADE and SNADE-cancer, cardiovascular, liver, and renal diseases) by %t(CD4<200) (continuous variable). We predicted survival probabilities for each event and calculated risks of hypothetical cases of different %t(CD4<200). Findings In 8,369 patients with 34 center dot 9 months of follow-up (median, IQR: 16 center dot 7, 69 center dot 1), 4,274 (51%) started ART with CD4<200 cells/mu L. Median %t(CD4<200) was 0% (IQR: 0, 15%). We identified 195 (2 center dot 3%) deaths and 584 (7 center dot 2%) patients with ADE/SNADE. For an increased %t(CD4< 200) of 15% (e.g., 15% vs. 0%), the adjusted relative hazard (aHR) of death was 1 center dot 27 (95% confidence interval [CI]: 1 center dot 19 - 1 center dot 35), of ADE/SNADE was 1 center dot 13 (95%CI: 1 center dot 09 - 1 center dot 17), of SNADE was 0 center dot 96 (95%CI: 0 center dot 89 - 1 center dot 02) and of death/ADE/SNADE was 1 center dot 11 (95%CI: 1 center dot 07 - 1 center dot 14). Estimates were similar after adjusting for time updated CD4 count. Interpretation In virologically suppressed PWH, increased time living with severe immunosuppression had an increased risk of death and ADE/SNADE in this Latin American cohort, independently of time updated CD4 count. Copyright (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)