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Objective: The source of residual HIV viremia is highly debated and its potential relationship with the HIV reservoir has not been clarified. Herein, we analysed the cell-associated HIV-DNA content in two important cell compartments of the HIV reservoir, resting CD4+ T memory (Trm) and peripheral T follicular helper (pTfh) cells, and the association with the residual HIV viremia in individuals with spontaneous HIV replication control (elite controllers, EC group) and in individuals with antiretroviral therapy (ART)-mediated HIV replication control (cART group)., Design: A cross-sectional study., Methods: Seventeen chronically HIV-infected patients with suppressed HIV replication were included. Cell-associated HIV-DNA was measured by ultrasensitive digital-droplet-PCR in purified Trm and pTfh cells. Residual HIV plasma viremia was quantified using a single-copy assay with a sensitivity of 0.3 HIV-RNA copies/ml., Results: A significant and positive correlation was demonstrated between HIV-DNA levels in pTfh cells and residual plasma viral load (rpVL) (rho = 0.928, P = 0.008) in HIV-positive elite controllers, but not in HIV-positive treated patients, despite the lower levels of cell-associated HIV-DNA found in elite controllers compared with cART patients in pTfh cells [176 (77-882) vs. 608 (361-860) copies/million cells, respectively; P = 0.05]., Conclusion: This association suggests that pTfh cells could have an important contribution to persistent viremia in elite controllers. This could be the consequence of a more limited control of HIV replication in elite controllers with higher transcriptional activity of HIV in pTfh cells of elite controllers than that in cART patients., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The HIV reservoir is the main barrier to eradicating HIV infection, and resting memory CD4 T (Trm) cells are one of the most relevant cellular component harboring latent proviruses. This is the first study analyzing the transcriptional profile of Trm cells, in two well-characterized groups of HIV patients with distinct mechanisms of viral replication control (spontaneous versus treatment-induced). We use a systems biology approach to unravel subtle but important differences in the molecular mechanisms operating at the cellular level that could be associated with the host's ability to control virus replication and persistence. Despite the absence of significant differences in the transcriptome of Trm cells between Elite Controllers (ECs) and cART-treated (TX) patients at the single gene level, we found 353 gene ontology (GO) categories upregulated in EC compared with TX. Our results suggest the existence of mechanisms at two different levels: first boosting both adaptive and innate immune responses, and second promoting active viral replication and halting HIV latency in the Trm cell compartment of ECs as compared with TX patients. These differences in the transcriptional profile of Trm cells could be involved in the lower HIV reservoir observed in ECs compared with TX individuals, although mechanistic studies are needed to confirm this hypothesis. Combining transcriptome analysis and systems biology methods is likely to provide important findings to help us in the design of therapeutic strategies aimed at purging the HIV reservoir. KEY MESSAGES: HIV-elite controllers have the lowest HIV-DNA content in resting memory CD4 T cells. HIV-ECs show a particular transcriptional profile in resting memory CD4 T cells. Molecular mechanisms of enhanced adaptative and innate immune response in HIV-ECs. High viral replication and low viral latency establishment associate to the EC status.

A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = -0.46, p = 0.043) and of CCR6 (rho = -0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.

HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay. Inter-group and intra-group differences were tested using non-parametric tests. Compared with the TX patients, the EC patients had smaller HIV reservoir not only in Trm but also in pTfh and non-pTfh subsets of memory CD4+ T-cells. The largest differences were observed in pTfh cells (p = 0.025). The pTfh and non-pTfh cells harbored similar levels of HIV-DNA in the EC (p = 0.60) and TX patients (p = 0.17); however, the contribution to HIV-DNA levels in memory CD4+ T-cells varied among the pTfh and non-pTfh subsets in both groups of patients. The EC patients showed smaller HIV reservoir in memory CD4+ cells, especially in the pTfh subset, a population of cells with a pivotal role in the antiviral immune response, suggesting a potential link between low levels of infection in pTfh cells and the ability of the EC patients to spontaneously control HIV replication.

Introduction: In 2009 a deep change in ARV treatment took place in Spain with the introduction of new ARV drugs. The principal objective of the study was to determine the clinical situation of the patients in which DRV/r was introduced in the ARV therapy., Methods: Observational, cross sectional and multicentre study in which 91 reference hospitals participated. Patient's enrollment was carried out between 2008 and 2009. Data were collected retrospectively considering standard clinical practice., Results: 719 medical records were reviewed. Patients had a different clinical situation compared to nowadays with predominance of multiresistant virus which leaded to virologic failure. The principal reason for introducing DRV/r in the ARV regimen was the virologic failure (54.2%)., Conclusions: Considering this situation, DRV/r became a therapeutic option which represented a change in the ARV paradigm in that period.

Introduction: GESIDA (AIDS Study Group) and the National AIDS Plan panel of experts propose "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients. These preferred regimens are based on the results of clinical trials, and on the opinions of the experts of the panel. The objective of this study is to evaluate the costs and the cost effectiveness of initiating treatment following these guidelines., Methods: Economic assessment of costs and cost effectiveness through the construction of decision trees. Effectiveness was defined as the probability of having viral load <50 copies/mL at week 48 in an intention-to-treat analysis. The perspective of the analysis is that of the National Health System, taking into account only the differential direct costs (ART, management of adverse effects, studies of resistance, and determination of HLA B * 5701). The area is Spain, the time horizon is 48 weeks, and the costs are those of 2011. A deterministic sensitivity analysis was performed, building three scenarios for each regimen: baseline, the most favourable, and the most unfavourable., Results: In the baseline scenario, the cost of initiating treatment ranges from 7,550 Euros for the ABC/3TC+EFV to 13,327 Euros for TDF/FTC+RAL. The efficacy ranges between 0.66 for ABC/3TC+LPV/r and 0.86 for TDF/FTC+RAL. Efficiency, in terms of cost effectiveness, varies between 10,175 and 15,539 Euros per responder at 48 weeks, for TDF/FTC/EFV and TDF/FTC+RAL respectively., Conclusion: The most efficient regimen was TDF/FTC+EFV, followed by ABC/3TC+EFV. Sensitivity analysis confirms the robustness of these findings., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)