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Coronavirus disease 2019 (COVID-19) might impact disease progression in people living with HIV (PLWH), including those on effective combination antiretroviral therapy (cART). These individuals often experience chronic conditions characterized by proviral latency or low-level viral replication in CD4+ memory T cells and tissue macrophages. Pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, can reactivate provirus expression in both primary cells and cell lines. These cytokines are often elevated in individuals infected with SARS-CoV-2, the virus causing COVID-19. However, it is still unknown whether SARS-CoV-2 can modulate HIV reactivation in infected cells. Here, we report that exposure of the chronically HIV-1-infected myeloid cell line U1 to two different SARS-CoV-2 viral isolates (ancestral and BA.5) reversed its latent state after 24 h. We also observed that SARS-CoV-2 exposure of human primary monocyte-derived macrophages (MDM) initially drove their polarization towards an M1 phenotype, which shifted towards M2 over time. This effect was associated with soluble factors released during the initial M1 polarization phase that reactivated HIV production in U1 cells, like MDM stimulated with the TLR agonist resiquimod. Our study suggests that SARS-CoV-2-induced systemic inflammation and interaction with macrophages could influence proviral HIV-1 latency in myeloid cells in PLWH.

This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells' susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF- β , and TNF- α ), and extracellular matrix components (collagen, α -SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2024 Cintia Cevallos et al.)

Liver fibrosis is the excessive accumulation of extracellular matrix proteins, primarily collagen, in response to liver injury caused by chronic liver diseases. HIV infection accelerates the progression of liver fibrosis in patients co-infected with HCV or HBV compared to those who are only mono-infected. The early event in the progression of liver fibrosis involves the activation of hepatic stellate cells (HSCs), which entails the loss of lipid droplets (LD) to fuel the production of extracellular matrix components crucial for liver tissue healing. Thus, we are examining the mechanism by which HIV stimulates the progression of liver fibrosis. HIV-R5 tropic infection was unable to induce the expression of TGF-β, collagen deposition, α-smooth muscle actin (α-SMA), and cellular proliferation. However, this infection induced the secretion of the profibrogenic cytokine IL-6 and the loss of LD. This process involved the participation of peroxisome proliferator-activated receptor (PPAR)-α and an increase in lysosomal acid lipase (LAL), along with the involvement of Microtubule-associated protein 1 A/1B-light chain 3 (LC3), strongly suggesting that LD loss could occur through acid lipolysis. These phenomena were mimicked by the gp120 protein from the R5 tropic strain of HIV. Preincubation of HSCs with the CCR5 receptor antagonist, TAK-779, blocked gp120 activity. Additionally, experiments performed with pseudotyped-HIV revealed that HIV replication could also contribute to LD loss. These results demonstrate that the cross-talk between HSCs and HIV involves a series of interactions that help explain some of the mechanisms involved in the exacerbation of liver damage observed in co-infected individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human immunodeficiency virus (HIV) neuroinvasion occurs early after infection through the trafficking of virus-infected immune cells into the central nervous system (CNS) and viral dissemination into the brain. There, it can infect resident brain cells including astrocytes, the most abundant cell type that is crucial to brain homeostasis. In this report, we examined the HIV-related mechanism able to induce bystander cell death in astrocytes mediated by cell-to-cell contact with productively infected (PI) ones. We first demonstrate that HIV-induced bystander cell death involves mitochondrial dysfunction that promotes exacerbated reactive oxygen species production. Such a phenomenon is a contagious cell death that requires contact with HIV-PI astrocytes that trigger caspase-dependent (apoptosis and pyroptosis) and caspase-independent cell death pathways. The HIV accessory proteins Nef, Vpu, and Vpr counteract astrocyte death among PI cells but, in contrast, participate to promote contagious bystander cell death by inducing mitochondrial reactive oxygen species production. Our findings indicate that astrocytes PI by HIV became capable to counteract infection-derived death signals, surviving, and spreading the bystander cell death into neighboring uninfected cells by a cell-to-cell contact-dependent mechanism. Considering that astrocytes have been proposed as a long-term HIV reservoir in the CNS, ascertaining the mechanism of survival and contagious bystander death will afford clear targets in the current goal to achieve a functional cure., (© 2022 International Society for Neurochemistry.)

Human immunodeficiency virus type 1 (HIV) primary drug resistance mutations (DRMs) influence the long-term therapeutic effects of antiretroviral treatment (ART). Drug-resistance genotyping based on polymerase gene sequences obtained by next-generation sequencing (NGS) was performed using samples from 10 ART-naïve HIV-infected men who have sex with men (MSM; P1-P10) from the acute/early to chronic stage of infection. Three of the 10 subjects exhibited the presence of major (abundance, ≥ 20%) viral populations carrying DRM at early/acute stage that later, at the chronic stage, dropped drastically (V106M) or remained highly abundant (E138A). Four individuals exhibited additional DRMs (M46I/L; I47A; I54M, L100V) as HIV minority populations (abundance, 2-20%) that emerged during the chronic stage but ephemerally.

As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV + -P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV - donors (HD). Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV + -P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4 + T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV + -P. Additionally, evidence of IgA interference with ADCC responses from HIV + -P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To present surveillance data on advanced disease (AD) and late presentation (LP) of HIV in Spain and their determinants., Methods: We included all new HIV diagnoses notified by the autonomous regions that consistently reported such cases throughout the period 2007-2011. Coverage was 54% of the total Spanish population. Data sources consisted of clinicians, laboratories and medical records. AD was defined as the presence of a CD4 cell count <200cells/μL in the first test after HIV diagnosis, while LP was defined as the presence of a CD4 cell count <350cells/μL after HIV diagnosis. Odds ratios and their 95% confidence intervals (OR, 95% CI) were used as the measure of association. Logistic regressions were fit to identify predictors of AD and LP., Results: A total of 13,021 new HIV diagnoses were included. Among these, data on the outcome variable were available in 87.7%. The median CD4 count at presentation was 363 (interquartile range, 161-565). Overall, 3356 (29.4%) patients met the definition of AD and 5494 (48.1%) were classified as LP. Both AD and LP increased with age and were associated with male sex and infection through drug use or heterosexual contact. All immigrants except western Europeans were more prone to AD and LP. Multivariate models disaggregated by sex showed that the effect of age and region of origin was weaker in women than in men., Conclusions: Despite universal health care coverage in Spain, men, immigrants and people infected through drug use or heterosexual contact seem to be experiencing difficulties in gaining timely access to HIV care., (Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.)

Objetive: To describe linkage to care among new HIV diagnoses in Spain; and to estimate factors associated to linkage to care within three months after diagnosis., Methods: The distribution of the time elapsing between the date of HIV diagnosis and the date of first determination of CD4 (considered to be the date of linkage to care) was calculated among new HIV diagnoses in 2010 in the seven Autonomous Regions participating, where data on date of CD4 count was available. Linkage to care was considered «correct» if done within three months after diagnosis. Factors associated to correct linkage to care were estimated using logistic regression., Results: A total of 1769 new HIV diagnoses were included. Of them, 83.1% had evidence of linkage to care within a year, and 75.7% were linked within three months after diagnosis. Being an injectable drug user (IDU) was the only factor inversely associated with linkage to care within 3 months (OR = 0.3; 95% CI: 0.2-0.6)., Conclusion: In Spain linkage to care after HIV diagnosis is good, but there is still room for improvement, especially among IDUs., (Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Objective: To describe the incidence of new HIV diagnoses and its trend in Spain., Methods: All new HIV diagnoses notified to the case-registries of 15 autonomous regions (64% of the total Spanish population) in 2009 were analyzed. To evaluate trends from 2004 to 2009, data from only nine regions were available. Clinical-epidemiological data were obtained from the notification forms. Distributions of new HIV diagnoses and late diagnoses according to several variables were performed. The Poisson distribution was used to evaluate trends., Results: In 2009, 2264 new HIV diagnoses were notified, mostly in men (80%). The median age at diagnosis was 36 years (interquartile range 29-43) and 37.6% of affected individuals were immigrants, mostly from Latin-America and sub-Saharan Africa. The most common transmission category (42.5%) was men who have sex with men (MSM) followed by the heterosexual and parenteral modes of transmission (34.5% and 8.1%, respectively). The median CD4 count at diagnosis was 347 (interquartile range: 152-555), and CD4 count was <350 in 50.2% of patients. From 2004 to 2009, the mean incidence rate of new HIV diagnoses was 91.14 per million inhabitants; an increasing trend for rates in MSM, as well as a decreasing trend for the parenteral mode of transmission, were observed., Conclusions: In Spain, the epidemiology of HIV infection has changed since the mid-1990s. Currently, the most frequent transmission category is sexual transmission, particularly among MSM, and immigrants are an important part of the epidemic. Heterogeneous trends for the three main transmission categories were observed from 2004 to 2009., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)