Long-term survival in HIV positive patients with up to 15 Years of antiretroviral therapy

Abstract

Background: Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models.

Methods: Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models.

Results: The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0-4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2-10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5-2.9) for CD4 = 350-499 cells/µl; and 1.5 (95% CI: 1.1-2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment.

Conclusion: Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

Figure 1. SMRs and 95% confidence intervals by years of cART and time updated CD4 cell count.

Blue/square markers represent patients with CD4<350 cells/µl. Green/round markers represent patients with CD4 from 350 to 499 cells/µl. Red/triangular markers represent patients with CD4≥500 cells/µl. Grey/horizontal dashed line represents SMR of 1.

Figure 2. SMRs and 95% confidence intervals by years of cART and time updated HIV viral load.

Blue/square markers represent patients with viral load ≤400 copies/ml. Green/round markers represent patients with HIV viral load >400 copies/ml. Grey/horizontal dashed line represents SMR of 1.

Figure 3. 10 year survival probabilities and 95% confidence intervals by age and time updated CD4 count.

Blue/square markers represent patients with CD4 less than 350 cells/µl. Green/round markers represent patients with CD4 from 350 to 499 cells/µl. Red/triangular markers represent patients with CD4≥500 cells/µl. Grey/horizontal dashed line represents Australian males 2008–09. These plots apply to patients on 4th or greater regimen, no prior HBVsAg, non-IDU mode of exposure and specified existing viral load and incidence of ADI. Plot (A) shows 10 year survival probabilities for patients with viral load ≤400 copies/ml and with no prior ADI. Plot (B) shows 10 year survival probabilities for patients with viral load ≤400 copies/ml and with prior ADI. Plot (C) shows 10 year survival probabilities for patients with viral load >400 copies/ml and with prior ADI.