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Objectives: The aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. Methods: We conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. Results: A total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be >2% at 3 years for baseline CD4 ≥350 cells/μL. Conclusion: Lower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

In spite of considerable hype to the contrary, there is no convincing evidence that currently existing so-called 'antiaging' remedies promoted by a variety of companies and other organizations can slow aging or increase longevity in humans. Nevertheless, a variety of experiments with laboratory animals indicate that aging rates and life expectancy can be altered. Research going back to the 1930s has shown that caloric restriction (also called dietary restriction) extends life expectancy by 30-40% in experimental animals, presumably at least partially by delaying the occurrence of age-dependent diseases. Mutations that decrease production of insulin growth factor I in laboratory mammals, and those that decrease insulin-like signaling in nematodes and fruit flies, have increased life expectancy as well. Other general strategies that appear promising include interventions that reduce oxidative stress and/or increase resistance to stress; hormone and cell replacement therapies may also have value in dealing with specific age-related pathologies. This article reports the findings of a consensus workshop that discussed what is known about existing and future interventions to slow, stop, or reverse aging in animals, and how these might be applied to humans through future research.