Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study

Background Some individuals remain AIDS-free with a high and stable CD4 cell count without antiretroviral therapy (ART) for many years. We estimated long-term progression-free survival after HIV seroconversion and aimed to identify factors associated with loss of long-term non-progression (LTNP) status. Methods For this cohort study, we used data for individuals with well-estimated dates of HIV-1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The first cohort began enrolling patients in 1979, and for this analysis we used data pooled in May 1, 2011. We defined non-progression as being HIV-positive without AIDS, ART-naive, and with CD4 counts of 500 cells per mu L or higher. We defined LTNP as non-progression during the first 10 years after seroconversion. We used longitudinal methods to characterise LTNP. Findings Of the 4979 HIV seroconverters in our dataset, 3708 (75%) were men. Median time to progression was 2.07 years (95% CI 1.96-2.17), giving estimated progression-free survivals of 18.4% (17.2-19.6) 5 years, 4.0% (3.6-4.5) 10 years, and 1.4% (0.9-1.5) 15 years after seroconversion. The rate of progression did not change beyond 10 years after seroconversion (0.28 [95% CI 0.26-0.31] per person-year at 10 years after seroconversion, 0.24 [0.19-0.29] per person-year at 15 years, and 0.18 [0.10-0.33] per person-year at 20 years). At 10 years since HIV seroconversion, 283 individuals had LTNP, of whom 202 subsequently lost this status (median time to loss of status 2.49 years [2.05-2.92]). In univariable analyses, loss of LTNP status was associated with CD4 cell count at 10 years after seroconversion (p <0.0001) and HIV RNA load at 10 years after seroconversion (p=0.005), but not age (p=0.544), mode of infection (p=0.621), sex (p=0.676), or calendar year of seroconversion (p=0.397). In the multivariable analyses, loss of LTNP status was associated with lower CD4 counts at 10 years after seroconversion (p <0.0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load at 10 years after seroconversion was independently associated with loss of LTNP status (p=0.009). Interpretation Progression-free survival is rare. Most individuals with LTNP eventually lose immunological and clinical control of HIV infection eventually