Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens

Abstract

Objectives To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. Methods This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50 copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350 cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. Results We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%–4.3%), 4.7% (95% CI 2.2%–7.1%) and 7.6% (95% CI 5.4%–9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3–0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. Conclusions In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China

“…Previous ndings [33][34][35] indicate older age may be a risk factor for incomplete CD4 + T cell recovery in PLWH, suggesting age may exert a strong effect on long-term recovery of CD4 + T cells. This was also found in the newly developed model, showing that median maximal CD4 + T cell count is higher in patients aged 16-32.5 years than in patients aged 32.5 years after ART treatment.…”

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China

“…Previous findings [ 32 , 36 , 37 ] indicate older age may be a risk factor for incomplete CD4 + T cell recovery in PLWH, suggesting age may exert a strong effect on long-term recovery of CD4 + T cells. This was also found in the newly developed model, showing that median maximal CD4 + T cell count is higher in patients aged 16–32.5 years than in patients aged 32.5 years after ART treatment.…”

Immune response to ART initiation in advanced HIV infection

“…In a multicentre European observational study, no difference in median CD4 cell count or CD4:CD8 ratio was observed 48 weeks after ART initiation with an INSTI or a PI among people with advanced HIV [4]. In the PISCIS cohort in Spain, people with advanced HIV were less likely to die and experienced faster virological suppression and CD4 cell count restoration when initiating ART with an INSTI than with a PI or non‐nucleoside reverse transcriptase inhibitors [5]. Similarly, among late‐presenting people with HIV (defined as CD4 <350 cells/μL or as either CD4 <350 cells/μL or ADE) in two Spanish cohorts, those initiating ART with an INSTI experienced favourable immunological outcomes compared with those initiating ART with other anchor agents [28, 32].…”

“…In the USA, the prevalence of advanced HIV was estimated at 22% in 2015; the prevalence increases with older age (up to 37% among individuals aged ≥55 years) and by transmission category (34% among men with infection attributed to heterosexual contact; 29% among men with infection attributed to injection drug use) [3]. Individuals presenting with advanced HIV infection have an increased risk of HIV clinical progression, morbidity, and mortality [4][5][6][7][8][9]. In addition, advanced HIV is associated with an increased risk of HIV transmission, due to both higher viral loads and a longer period with unsuppressed viremia [6].…”