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Objectives: A sizeable percentage of individuals infected by HIV and on antiretroviral therapy (ART) fail to increase their CD4 T-cells to satisfactory levels. The percentage of regulatory T-cells (Tregs) has been suggested to contribute to this impairment. This study aimed to address this question and to expand the analysis of Tregs subpopulations during ART., Design: Longitudinal follow-up of 81 HIV-infected individuals during the first 24 months on ART., Methods: CD4 T-cell counts, Tregs percentages, and specific Tregs subpopulations were evaluated at ART onset, 2, 6, 9, 12, 16, 20, and 24 months of ART (five individuals had no Tregs information at baseline)., Results: The slope of CD4 T-cell recovery was similar for individuals with moderate and with severe lymphopenia at ART onset. No evidence was found for a contribution of the baseline Tregs percentages on the CD4 T-cell counts recovery throughout ART. In comparison to uninfected individuals, Tregs percentages were higher at ART onset only for patients with less than 200 cells/μl at baseline and decreased afterwards reaching normal values. Within Tregs, the percentage of naive cells remained low in these patients. Reduced thymic export and increased proliferation of Tregs vs. conventional CD4 T cells might explain these persistent alterations., Conclusion: No effect of Tregs percentages at baseline was detected on CD4 T-cell recovery. However, profound alterations on Tregs subpopulations were consistently observed throughout ART for patients with severe lymphopenia at ART onset.

Purpose of Review: To discuss factors related to virologic failure and review data from recent clinical trials evaluating re-suppression of viremia in extensively-treated HIV-infected patients with resistance., Recent Findings: Factors associated with virologic failure can be related to the virus (e.g. resistance), the patient (e.g. adherence) or HIV therapy (e.g. availability) and must be analyzed to minimize the likelihood of a new failure. Recent clinical trials have shown that it is now possible to achieve virologic suppression in a large proportion of treatment-experienced patients with extensive drug resistance, with several newer agents demonstrating favorable potency, tolerability and long-term efficacy., Summary: The benefits of highly active antiretroviral treatment are well recognized, and adding at least two (preferably three) new active drugs to an optimized background regimen can provide effective suppression of viremia even in multidrug-experienced patients. Changing drugs or regimen simplification should be considered when treatment is inadequate, poorly tolerated or associated with poor adherence, and is made easier by the newer agents and formulations now available. Newer antiretrovirals may contribute to a better quality of life and life expectancy in patients with few or no therapy options, although adherence is paramount in ensuring their continued effectiveness.