title: Are long-term non-progressors very slow progressors? Insights from the Chelsea and Westminster HIV cohort, 1988-2010.
abstract: Define and identify long-term non-progressors (LTNP) and HIV controllers (HIC), and estimate time until disease progression. LTNP are HIV-1(+) patients who maintain stable CD4(+) T-cell counts, with no history of opportunistic infection or antiretroviral therapy (ART). HIC are a subset of LTNP who additionally have undetectable viraemia. These individuals may provide insights for prophylactic and therapeutic development. Records of HIV-1(+) individuals attending Chelsea and Westminster Hospital (1988-2010), were analysed. LTNP were defined as: HIV-1(+) for >7 years; ART-naïve; no history of opportunistic infection and normal, stable CD4(+) T-cell counts. MIXED procedure in SAS using random intercept model identified long-term stable CD4(+) T-cell counts. Survival analysis estimated time since diagnosis until disease progression. Subjects exhibiting long-term stable CD4(+) T-cell counts with history below the normal range (<450 cells/µl blood) were compared to LTNP whose CD4(+) T-cell count always remained normal. Within these two groups subjects with HIV-1 RNA load below limit of detection (BLD) were identified. Of 14,227 patients, 1,204 were diagnosed HIV-1(+) over 7 years ago and were ART-naïve. Estimated time until disease progression for the 20% (239) whose CD4(+) T-cell counts remained within the normal range, was 6.2 years (IQR: 2.0 to 9.6); significantly longer than 4.0 years (IQR: 1.0 to 7.3) for patients with historical CD4(+) T-cell count below normal (Logrank chi-squared = 21.26; p<0.001). Within a subpopulation of 312 asymptomatic patients, 50 exhibited long-term stable CD4(+) T-cell counts. Of these, 13 were LTNP, one of whom met HIC criteria. Of the remaining 37 patients with long-term stable low CD4(+) T-cell counts, 3 controlled HIV-1 RNA load BLD. Individuals with stable, normal CD4(+) T-cell counts progressed less rapidly than those with low CD4(+) T-cell counts. Few LTNP and HIC identified in this and other studies, endorse the need for universal definitions to facilitate comparison.
authors.affiliation: Department of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandalia
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Westrop
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Beck
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Brian G
authors.initials: BG
authors.lastname: Gazzard
authors.forename: Nesrina
authors.initials: N
authors.lastname: Imami
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003710:Demography; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008131:London; D008297:Male; D013997:Time Factors