CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus

• Published in: Journal of antimicrobial chemotherapy 2017-10, Vol.72 (10), p.2862-2868
• Main Authors: Ghosn, Jade, Bayan, Tatiana, Meixenberger, Karolin, Tran, Laurent, Frange, Pierre, d'Arminio Monforte, Antonella, Zangerle, Robert, de Mendoza, Carmen, Krastinova, Evguenia, Porter, Kholoud, Meyer, Laurence, Chaix, Marie-Laure
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - therapeutic use; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cohort Studies; Disease Progression; env Gene Products, Human Immunodeficiency Virus - genetics; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Seropositivity - immunology; HIV Seropositivity - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - physiology; Humans; Kinetics; Male; Receptors, CXCR4 - metabolism; Viral Load; Viral Tropism
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkx247

The natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.