Impact of Latent M. tuberculosis Infection Treatment on Time to CD4/CD8 Recovery in Acute, Recent, and Chronic HIV Infection

Abstract

Introduction: In PLWH, active and latent TB co-infections are associated with immune activation that correlate with HIV progression and mortality. We investigated the effect of initiating ART during acute (AHI), recent (RHI), or chronic HIV infection (CHI) on CD4/CD8 ratio normalization and associated factors, the impact of latent tuberculosis infection (LTBI) treatment, and prior/concomitant tuberculosis (TB) diagnosis at time of ART initiation. Methods: We included MSM and TGW individuals initiating ART with AHI, RHI and CHI between 2013-2019, from a prospective cohort in Brazil. We compared time from ART initiation to the first normal CD4/CD8 ratio (CD4/CD8≥1) using Kaplan Meier curves and multivariable Cox proportional hazards models. Sociodemographic and clinical variables were explored. Variables with p-values<0.20 in univariable analyses were included in multivariable analyses. Results: 550 participants were included, 11.8% classified as AHI and 6.4% as RHI, 46.7% with CHI-CD4 cell counts≥350cells/mm3 and 35.1% with CHI-CD4 cell counts<350cells/mm3. Time to normalization was shortest among AHI patients, followed by RHI and CHI individuals with higher baseline CD4. In the multivariable model AHI was associated with a six-fold increased likelihood of achieving a CD4/CD8ratio ≥1 (HR:6.03;95%CI3.70-9.82;p<0.001), RHI with HR:4.47(95%CI2.57-7.76;p<0.001) and CHI CD4≥350cells/mm3 with HR:1.87(95%CI1.24-2.84;p=0.003). LTBI treatment was significantly associated with a higher likelihood of the outcome (HR:1.79;95%CI1.22-2.62;p=0.003). Prior history or concomitant active TB at ART initiation was associated with a lower likelihood of the outcome (HR:0.41;95%CI0.16-1.02;p=0.054). Conclusions: Initiating ART early during AHI may offer an opportunity to mitigate immune damage. Efforts to implement HIV diagnosis and ART initiation during AHI are critical to amplify ART benefits.