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.
Highlights
The majority of HIV-1 infected patients display a gradual decline in peripheral blood CD4+ T cells throughout the course of their illness
AIDS defining illnesses were originally used as clinical indicators of HIV-1 disease progression, in 1993 the USA widened their definition of AIDS to include a decline in peripheral blood CD4+ T-cell count to less than 200 cells/ml blood or less than 14% of lymphocytes [4]
The aims of this study were firstly, to estimate the time until HIV-1 disease progression in groups of patients identified as long-term non-progressors (LTNP) during the study period by the application of different selection criteria; secondly to identify the frequency of HIV-1+ patients belonging to the Chelsea and Westminster HIV cohort who, at the end of the study period, fulfilled the criteria of LTNP and HIV controllers (HIC); and thirdly, to report immunological and virological profiles in the patient groups identified
Summary
The majority of HIV-1 infected patients display a gradual decline in peripheral blood CD4+ T cells throughout the course of their illness. Some HIV-1+ patients are able to maintain stable CD4+ T-cell counts within the normal healthy range (between 450–1650 cells/ml blood; local laboratory reference range [5]) for a prolonged length of time and remain asymptomatic without antiretroviral therapy (ART). These patients have been referred to as long-term non-progressors (LTNP). Within this group of atypical patients a few, known as HIV controllers (HIC), suppress HIV-1 replication below the limit of detection of the HIV-1 RNA plasma load assay (BLD; ,50 HIV-1 RNA copies/ ml plasma) [5,6]. Confusion about definitions used exists in the published literature, resulting in difficulties when comparing results from patient groups within different cohorts
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