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A low CD4/CD8 ratio during antiretroviral therapy (ART) identifies people with heightened immunosenescence and increased risk of mortality. We aimed to assess the effects of integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART on long-term CD4/CD8 ratio recovery.

To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action. Rats were implanted with a four‐contact cylindrical mini‐lead and randomly assigned to two control (no‐pain and pain model) and five test groups featuring monophasic, as well as charge‐unbalanced and charge‐balanced biphasic SCS waveforms. Mechanical and cold allodynia were assessed to measure efficacy. The ipsilateral dorsal quadrant of spinal cord adjacent to the lead was harvested post‐stimulation and processed to determine gene expression via real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR). Gene expression, SCS intensity (mA), and behavioral score as percent of baseline (BSPB) were statistically analyzed and used to generate correlograms using R‐Studio. Statistical analysis was performed using SPSS22.0, and p< 0.05 was considered significant. As expected, BSPB was significantly lower for the pain model group compared to the no‐pain group. BSPB was significantly improved post‐stim compared to pre‐stim using cathodic, anodic, symmetric biphasic, or asymmetric biphasic 1:2 waveforms; however, BSPB was not restored to Sham levels. RT‐PCR analysis showed that eight genes demonstrated a significant difference between the pain model and SCS waveforms and between waveforms. Correlograms reveal a linear correlation between regulation of expression of a given gene in relation to mA, BSPB, or other genes. Our results exhibit that specific SCS waveforms differentially modulate several key transcriptional pathways that are relevant in chronic pain conditions. These results have significant implications for SCS: whether to move beyond traditional paradigm of neuronal activation to focus also on modulating immune‐driven processes.

Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137–0.994, p = 0.049). Also, a negative correlation between miR-21 expression and MCP-1 level was found (r = −0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found.

ABSTRACTWhile the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom mycobiome–bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We included 24 PWH individuals and 12 healthy controls. We sequenced the Internal Transcribed Spacer 2 amplicons, determined amplicon sequence variants, measured biomarkers of the innate and adaptive immunity in blood and relations with diet. Compared to healthy controls, PWH subjects exhibited a distinct and richer mycobiome and an enrichment for Debaryomyces hansenii, Candida albicans, and Candida parapsilosis. In PWH, Candidaand Pichiaspecies were strongly correlated with several bacterial genera, including Faecalibacteriumgenus. Regarding the links between the mycobiome and systemic immunology, we found a positive correlation between Candidaspecies and the levels of proinflammatory cytokines (sTNF-R2 and IL-17), interleukin 22 (a cytokine implicated in the regulation of mucosal immunity), and CD8+ T cell counts. This suggests an important role of the yeasts in systemic innate and adaptive immune responses. Finally, we identified inter-kingdom interactions implicated in fiber degradation, short-chain fatty acid production, and lipid metabolism, and an effect of vegetable and fiber intake on the mycobiome. Therefore, despite the great differences in abundance and diversity between the bacterial and fungal communities of the gut, we defined the changes associated with HIV, determined several different inter-kingdom associations, and found links between the mycobiome, nutrient metabolism, and systemic immunity.

The absence of direct clinical symptoms clearly associated to HTLV-2 infection may partially explain an underestimate of the real HTLV-2 prevalence rate and its effects in patients concurrently infected with HIV-1 and hepatitis C virus (HCV). Hence, to date, the influence of HTLV-2 on hepatic fibrosis has been poorly studied.

Antiretroviral therapy (ART) intensification has been shown to reduce the reservoir of latently infected CD4T cells. However, it is currently unknown whether this effect is maintained after discontinuation of the intensifying drug.

Immunovirologic parameters of 24 heavily antiretroviral drug-pretreated patients with prolonged virologic treatment failure under highly active antiretroviral therapy, and who harbored highly resistant human immunodeficiency virus (HIV) isolates, were studied in this retrospective cross-sectional study. Most of the patients were injecting drug users (71%) and male (88%). All patients were studied for CD4+ cell count, HIV viral load, resistance mutations, and viral phenotype. The patients showed a high accumulation of resistance-associated mutations, their CD4+ cell count and viral load directly correlated with their respective values at initiation of therapy, and the presence of K103N was inversely associated with lower viral load. On the other hand, patients with K103N had the same level of CD4+ cell count compared with patients without this mutation. Among the patients, a majority with a specific viral phenotype was not present. Rather, a dual-tropic virus was found most frequently, suggesting a preferential suppression of X4-specific strains and less cytopathogenicity during antiretroviral therapy and a greater proportion of R5X4 viruses due to an adaptation to that pressure.

The thymus involutes with age and its functionality has traditionally been assumed to be limited early in life. However, some studies have demonstrated that thymic function persists in adults. In humans, since it is difficult to obtain thymic samples from healthy individuals, indirect parameters have been used to study the thymic function. The aim of this study was to compare thymic function parameters within both the thymus and peripheral blood mononuclear cells from thirty-three patients who underwent cardiac surgery, as well as to relate these parameters with aging. The proportion of peripheral naïve T cells and intrathymic T cell differentiation stages, as well as peripheral and intrathymic TREC levels were analysed. We demonstrated that thymopoyesis persists in the healthy elderly since all T cell differentiation stages were found within the thymus. Among the studied parameters, peripheral TREC levels are found to be a good thymic function marker since they correlated with age. In healthy individuals, peripheral TREC levels are a good reflect of thymic function as demonstrated by their correlation with intrathymic TREC values.

One of the strategies that has been investigated to reduce antiretroviral treatment toxicity in patients infected with human immunodefiency virus (HIV) is structured treatment interruption (STI). Our aim was to analyze early viral and immune dynamics after interruption of highly active antiretroviral therapy (HAART) and to determine whether thymic function–related markers play a role in preventing CD4 count decline caused by increased viral replication. This was a prospective study of an open cohort of 47 HIV-infected patients with a median 969 CD4 count and prolonged viral suppression. They were followed every 4 weeks though week 24. Thymic volume and TREC level were analyzed at baseline. Increased thymic volume was associated with higher plasma viral load and greater CD4 count decline early after interruption. Three virologic patterns were observed: rapid/high (RH), delayed/high (DH), and low/slow (LS) viral replication. RH correlated with higher thymic volume at baseline and with higher CD4 count decline at week 4. Patients with greater thymic volume was associated with an immune and virologic impairment only early after interruption, probably because of infection of the increased number of available target cells. As the long-term consequences of these observations are unknown, the safety of treatment interruption must be further studied.

Abstract Whether HAART allows complete recovery of humoral immune function in HIV-infected individuals is still controversial. Our objective was to study the effect of HAART on both B cell repopulation and hypergammaglobulinemia in 72 naïve patients, including 35 HCV-coinfected individuals, during 156 weeks on HAART. The possible role of HCV coinfection on the recovery of the humoral immune system was also investigated. At baseline, HCV-coinfected patients had greater circulant IgG levels than HIV-only-infected patients, while B cell count and CD21low B cell subpopulation were similar in both groups. During HAART, HIV-only-infected patients reached normal B cell counts and circulant IgG levels, while HCV-coinfected individuals did not. CD21low B cell subpopulation significantly decreased in both groups of patients at week 48 after the initiation of HAART compared to baseline. Thus, B cells remained continuously stimulated in HCV-coinfected patients and this stimulation seemed to be through a CD21-independent pathway.

Objective: To assess the durability of the undetectability of HIV plasma viraemia (pV) and to determine the factors associated with virological rebound (VR) in HIV-infected adults on protease inhibitor (PI)-sparing highly active antiretroviral therapy (HAART). The development of resistance mutations during virologically successful therapy and VR was also analysed. Materials and methods: One hundred and twenty-six HIV-infected adults on PI-sparing HAART were prospectively followed from April 1998 to December 2002: Group 1, naive for antiretroviral drugs (n &equals; 26); Group 2, previously PI-HAART-exposed patients (n &equals; 19); Group 3, previously exposed to suboptimal therapy (n &equals; 81). Genotypic resistance tests on peripheral blood mononuclear cells or on plasma RNA (when feasible) were carried out when undetectable HIV pV was demonstrated for at least 48 weeks. Additionally, patients showing a therapy adherence >95&percnt; developing VR were also tested at rebound, at simplification and during previous suboptimal therapy exposure. Results: The median follow-up time was 630 &lsqb;329–903&rsqb; days. VR was considered as two consecutive pV levels >50 copies/mL. Twenty-two (17.5&percnt;) patients developed VR. Only therapy adherence <95&percnt; was independently associated with VR (adjusted hazard ratio: 8.42; 95&percnt; CI: 3.33–21.27). Twenty (40&percnt;) of the 50 patients with pV < 50 copies/mL for at least 48 weeks showed at least one thymidine-associated mutation (TAM) but none had NNRTI-resistance mutations. Ten (83.3&percnt;) of 12 available adherent patients showing VR harboured NNRTI-resistance-associated mutations; 50&percnt; of them were considered as wild-type strains at simplification time. However, the TAM number and resistance mutations profile found on suboptimal exposure were very similar to those found at VR on simplification therapy. Conclusions: PI-sparing HAART allows maintenance of successful long-term control of HIV replication, adherence to therapy being the main factor associated with VR. However, a small proportion of patients on simplification regimen may develop VR regardless of therapy compliance. VR on PI-sparing HAART is characterized by the emergence of NNRTI cross-resistance mutations. Finally, TAMs ‘archived’ during previous suboptimal exposures are partially involved in subsequent VR on simplification HAART.

HTLV-I isolates exhibit peculiar geographic distributions, but are believed not to be associated with different pathogenic outcomes of these retroviral infections. We have analyzed two HTLV-I-infected Spanish native patients: one patient with a T-cell lymphoma had not travelled to HTLV endemic areas, and the other patient had a paraparesis and had travelled to many HTLV endemic areas such as South America, and Central and South Africa. LTR proviral sequences of these isolates were amplified and sequenced to generate phylogenetic trees with different reported HTLV-I strains in order to subtype them. Spanish isolates clustered into the cosmopolitan HTLV-Ia subtype. It is important to know which HTLV-I subtypes are circulating in Spain. It is possible that a subtype other than the cosmopolitan one is present in Spain, especially African subtypes due to the proximity of this continent and the rise of immigration from Central and South African countries.

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Background The human T-lymphotropic virus type I (HTLV-I) has been implicated in the genesis of tropical spastic paraparesis (TSP), adult T-cell lymphoma (ATL), and some cases of uveitis, subacute arthropathies, chronic dermatitis and lymphocytic alveolitis. The virus is endemic in some areas of the Caribbean basin, Japan, subSaharan Africa, Central and South America, Middle East and Melanesia. Given that HTLV-I is transmitted through similar ways to HIV, screening in blood donors is recommended in some countries. Material and Methods The clinical, epidemiological and virological characteristics of 27 patients with HTLV-I infection were identified in Spain up to September 1995. Results Eighteen cases were Spanish natives and 9 were immigrants from endemic areas. Fifteen were male and 12 were female. The majority (12/18; 66.7%) of subjects born in Spain had resided in endemic areas or had had sexual partners from these regions. Four patients had TSP, three had ATL and one developed lymphomatous granulomatosis and T-cell lymphoma. The remaining HTLV-I subjects were asymptomatic at the time of diagnosis. Four cases were identified from screening of blood donors. Conclusion HTLV-I is present in Spain, affecting natives and, less frequently, immigrants from endemic areas. Both neurological and lymphoproliferative diseases have been recognized in a quarter of patients.