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.

Figure 1. Flow chart detailing the identification of LTNP and patients with long-term stable low CD4⁺ T-cell counts from the Chelsea and Westminster HIV Cohort, during the study period 1988–2010.

Figure 2. CD4⁺ T-cell counts over the time since HIV-1⁺ diagnosis of (A) 13 LTNP, one of whom fulfilled HIC status, with VLBLD, as detailed in the key and (B) 37 patients with long-term stable low CD4⁺ T-cell count, 3 of whom maintained HIV-1 RNA load to BLD.

Dashed horizontal lines indicate the normal healthy range of CD4⁺ T-cell count (450–1650 cells/µl blood), and a solid vertical line shows the time point 7 years post HIV-1⁺ diagnosis. Repeated CD4 T-cell counts are plotted at the time points indicated, where different symbols represent different individual patients.

Figure 3. Synonyms used to describe HIV-1⁺ patients exhibiting atypical disease progression.

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