This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). The findings warrant further investigation of ART in HIV preex... Visual Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving ART This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving ant... Background: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. Obj...

Objective: The protein kinase C (PKC) agonist bryostatin-1 has shown significant ex-vivo potency to revert HIV-1 latency, compared with other latency reversing agents (LRA). The safety of this candidate LRA remains to be proven in treated HIV-1-infected patients. Methods: In this pilot, double-blind phase I clinical-trial (NCT 02269605), we included aviraemic HIV-1-infected patients on triple antiretroviral therapy to evaluate the effects of two different single doses of bryostatin-1 (10 or 20 μg/m²) compared with placebo. Results: Twelve patients were included, four in each arm. Bryostatin-1 was well tolerated in all participants. Two patients in the 20 μg/m² arm developed grade 1 headache and myalgia. No detectable increases of cell-associated unspliced (CA-US) HIV-1-RNA were observed in any study arm, nor differences in HIV-1 mRNA dynamics between arms (P = 0.44). The frequency of samples with low-level viraemia did not differ between arms and low-level viraemia did not correlate with CA-US HIV-1-RNA levels (P = 0.676). No changes were detected on protein kinase C (PKC) activity and in biomarkers of inflammation (sCD14⁺ and interleukin-6) in any study arm. After the single dose of bryostatin-1, plasma concentrations were under detection limits in all the patients in the 10 μg/m² arm, and below 50 pg/ml (0.05 nmol/l) in those in the 20 μg/m² arm. Conclusion: Bryostatin-1 was safe at the single doses administered. However, the drug did not show any effect on PKC activity or on the transcription of latent HIV, probably due to low plasma concentrations. This study will inform next trials aimed at assessing higher doses, multiple dosing schedules or combination studies with synergistic drugs.

Background: Sexualized drug use (SDU), also known as chemsex, refers to the use of psychoactive substances for sexual purposes among men who have sex with men (MSM), which has been associated with mental health symptoms. The objective of this review is to systematically review the available evidence on mental health outcomes in MSM who use sexualized drugs. Methods: To prepare this systematic review, search strategies were developed and applied to the Web of Science, Science Direct, PubMed, and Scopus databases. A total of 117 articles were found, of which 12 were selected for the final review. Results: Those MSM who practiced SDU were more likely to experience from depression, anxiety, or a substance dependence, although these results were not found in all the studies analyzed. Among those who practiced the administration of intravenous drugs (referred to as slamsex), the mental health symptoms were more severe. Conclusions: This systematic review contributes to a fuller understanding of the mental health symptoms present in MSM who consume drugs for sexual purposes. Greater uniformity in data collection instruments is required, as well as the need to conduct a more in-depth assessment of the psychosocial adjustment of people who practice chemsex.

The primary objective was to assess the effect of MVC intensification on latently infected CD4⁺ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4⁺ or CD8⁺ counts, although a significant decrease was found in the proportion of HLA-DR⁺/CD38⁺ CD4⁺ and CD8⁺ T-cells. LPS and sCD14 levels increased. Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. ClinicalTrials.gov NCT00795444

In the last decade, studies in persons with HIV (PWH) on antiretroviral therapy (ART) have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low CD4/CD8 ratio reflects increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of the CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cutoff points, associated clinical events, effects of treatments, and how the CD4/CD8 ratio could improve decision making in the clinic. Here, we critically review the literature, identify knowledge gaps, and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.

Objectives: The stability of the reservoir of latently infected memory CD4⁺ T-cells may be associated with continuous replenishment from residual HIV-1, not completely eliminated by otherwise successful antiretroviral therapy (ART). Treatment intensification could help to control residual virus and to modify the latent reservoir. The objective of this work is to assess the effect of intensifying therapy with raltegravir on the HIV-1 cell reservoir. Design: A pilot open-label phase-II clinical trial was performed to analyze ART intensification with raltegravir after 48 weeks in chronically HIV-1-infected patients on stable ART. Methods: We measured the number of latently infected memory CD4⁺ T cells, residual viremia, 2-long terminal repeat circles, CD4⁺/CD8⁺ T-cell activation, lymphocyte subpopulations, gut homing receptor, and bacterial translocation. Results: A significant decay of HIV-1 latent reservoir was observed after intensification in the nine patients included (P = 0.021). No variation was found in either residual viremia or 2-long terminal repeat circles, whereas CD8⁺ T-cell activation decreased at week 36 (P = 0.028). No differences were found in naive T-cell or effector memory cell counts, and the frequencies of gut homing receptor on activated or effector memory CD8⁺ T cells. Bacterial translocation was stable, with the exception of a late decrease in lipopolysaccharide levels. Conclusions: In this pilot noncomparative trial, treatment intensification with raltegravir significantly decreased the latent cellular HIV-1 reservoir and CD8⁺ T-cell activation. Despite the limitations inherent to trial design, our results suggest that ART intensification should be considered as an adjuvant strategy to eradicate HIV-1 infection.